NIHRDataInsights/HRCSData huggingface dataset:
Title: PHOSP-COVID Post-hospitalisation COVID-19 study: a national consortium to understand and improve long-term health outcomes
Funder: Medical Research Council

Abstract: The SARS-CoV-2 (COVID-19) pandemic, has caused significant mortality and morbidity, alongside economic, psychological and societal effects. Over 100,000 people have been hospitalised in the UK with an in-hospital mortality of 26%. In addition to severe pneumonia, there is evidence of widespread pathology beyond the lung. To understand and improve long-term outcomes for survivors following hospitalisation with COVID-19, we shall establish a national platform embedding research into a standardised clinical pathway and biosampling integrated with ISARIC-4C and utilising the NIHR Bioresource. This will enable detailed clinical phenotyping of individuals. We propose to analyse routine clinical data with linkage to retrospective and prospective health and social care records (Tier 1), enhanced clinical data and research-specific biosampling (Tier 2) and re-call of participants by genotype and phenotype for more detailed studies (Tier 3). We shall recruit 10000 individuals with a minimum of 5000 in Tier 2. We aim to i) determine the short to long-term chronic health (and health economic) sequelae of COVID-19 infection in post-hospitalisation survivors; to define demographic, clinical and molecular biomarkers of the susceptibility, development, progression and resolution of these health sequelae, ii) to understand the impact of interventions during the acute illness on these long-term sequelae and iii) to build the foundation for multiple indepth studies e.g. lung fibrosis, pulmonary and systemic vasculature, cardiometabolic, renal, sarcopaenia, rehabilitation, mental health and neurological disease. Our findings will inform precision medicine in at risk groups by directing new clinical trials and care for current and future post-COVID-19 patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: COPE-Birmingham: The contribution of occupational exposures to risk of COVID-19 and approaches to control among healthcare workers
Funder: Medical Research Council

Abstract: Occupational exposures may contribute to higher risk of COVID-19 disease among healthcare workers (HCW). Using two linked case control studies, we aim to estimate the relative importance of occupational exposures and non-workplace related factors in risk of infection. Additional longitudinal follow-up of the participants will allow us to examine risks among asymptomatic carriers, determine antibody durability and track the pandemic evolution in HCW. We will recruit 5000 HCW from diverse backgrounds and job-roles within three large NHS Trusts in West Midlands. Participants will include HCW with COVID-19 symptoms and have had PCR tests, as well as 1000 of those without symptoms. Cases are HCW with positive PCR results and controls will be a matched sample of those tested negative. We will collect data on personal and health characteristics, type/nature of work, extent and type of interaction with COVID-19 patients, and ability to use recommended infection control procedures. Those with positive tests will be asked about symptoms in household members and the symptomatic ones will be tested for SARS-CoV-2. We will compare occupational and other characteristics by PCR status to examine the relative contribution of occupational and non-workplace risk factors. Participants will be followed up, with blood tests for SARS-CoV-2 antibodies at 3-months and repeated at 6 months. Using interviews with up to 30 purposively selected staff and 20 managers, we will explore access to and use of infection control procedures, to understand any barriers or facilitators. The findings will inform future workplace policies and resource allocation decisions.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION
Title: Investigating incidence, severity and risk factors for COVID-19 in BAME and Migrant groups to inform public health action.
Funder: Medical Research Council

Abstract: QUESTION: How can we understand and reduce the differential impact of COVID-19 on Black, Asian and Minority Ethnic (BAME) and migrant groups? WP1: BAME INCLUSION BOOST TO VIRUS WATCH Methods: 12,600 additional Black African, Black Caribbean, Indian, Bangladeshi, Pakistani and Polish across England and Wales- July 2020-June 2021. Baseline serology (n=3000) and survey, weekly symptom follow-up, PCR swabbing on day 2 of illness, monthly follow-up surveys, serology at end of study. Outcomes: Seroprevalence, incidence, household transmission, symptom severity, mortality, mental health and economic impacts of pandemic and control measures. Explanatory Factors: Ethnicity, migration, immunity, occupation, housing, socioeconomic, behaviour, healthcare usage (and barriers in access), contact patterns (including intergenerational contact), co-morbidities. WP2: MILLION MIGRANT AND MINORITY ETHNIC COHORTS. Data sources: Unique datasets including the majority of non-EU migrants and resettled refugees since 2015, characterised by migration and ethnicity (n=1.7 million migrants, 20,000 refugees, 2.0 million BAME). Linkage: Previously validated probabilistic/deterministic algorithms to link to national COVID-19 laboratory data, hospitalisation, mortality data. Outcomes: Differential SARS-CoV-2 infection, COVID-19 hospitalisations and deaths over first wave and winter 2020/21. Explanatory Factors: Ethnicity, year of migration and immigration category, country of origin and birth, age, gender, language proficiency, comorbidities. KEY REPORTS. Dashboard-based real-time reporting of differential disease occurrence and contact patterns. Autumn 2020: Differential impacts of the first wave and effect of easing lockdown. Spring 2021: Differential impact of winter COVID-19 and other respiratory infections. DISSEMINATION AND PARTNERS: PHE, NHS, Race Equality Foundation and Doctors of The World.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: TraCK Transmission of COVID19 in Kids
Funder: Medical Research Council

Abstract: To develop refined models of the COVID-19 epidemic, and predict impact of different public health interventions, we need to understand far more about transmission of SARS-CoV2 between children and between children and adults. In contrast to adults, syndromic surveillance for COVID-19 in children is wholly insufficient, as disease is largely asymptomatic; sequential intensive testing of oral/nasopharyngeal samples is the only method to quantify or rule out transmission events. Outbreak investigation with multiple cases often occurs at too late a stage to infer transmission routes. Exploiting statutory notification systems as a trigger for rapid deployment, the study will explore two 'low signal' scenarios (i) community COVID-19 activity and (ii) single case in a school- child, teacher, other adult Through a sequence of individual school cohort studies, in schools exposed to a low signal event, we will be uniquely placed to use intense longitudinal sampling of children and environment coupled with advanced virology, to address the following questions 1. Do symptomatic or asymptomatic children transmit the virus (a) to each other? (b) to adults in schools or household? Or are adults more likely to be the source of infection in children? 2. What are the likely modes of transmission in the event of a positive case? (a) do classrooms or washrooms/toilet become contaminated? (b) is virus found in the air? (c) is virus present in saliva or on hands of infected children? 3. How long do infected children carry viable infectious virus and when do secondary cases arise if at all?


Research activity codes: 4.4 POPULATION SCREENING;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION
Title: Safety and lower airway immunogenicity of two candidate Coronavirus Disease (COVID-19) vaccines administered to the respiratory tract
Funder: Medical Research Council

Abstract: Substantial literature indicates that stimulation of mucosal immunity by direct antigen delivery can induced tissue-specific responses that are more effective in preventing respiratory disease, limiting viral shedding and interrupting transmission. However, in order to proceed rapidly, all COVID-19 vaccines currently in development are administered by parenteral injection. The aim of this study is to test the safety and mucosal immunogenicity of the two leading UK COVID-19 vaccines (ChAdOx1 nCoV19 and LNP-nCoV RNA) when administered by aerosol in healthy adult volunteers. Each vaccine will be administered at 3 dose levels (in groups of 3 participants) with a further 6 individuals vaccinated with the highest tolerated dose. Systemic immunogenicity will be quantified using standardised assays for SARS-CoV-2 antibodies (by ELISA and virus neutralisation) and T cells (by IFN-g ELISpot). Serology will be performed in the same laboratory as the ongoing phase I/II/III trials of intramuscular ChAdOx1 nCov19, allowing direct data comparison. Additionally, all participants will undergo bronchoscopic sampling of the lower airway at pre-vaccination, day 21 and day 182 timepoints. Together with nasal specimens, these will be analysed for mucosal IgA, T cells by intracellular cytokine staining and flow cytometry, and soluble mediators by MesoScale Discovery using techniques aligned with previous human respiratory virus challenge studies. Thus, we will provide proof-of-concept that these vaccines can safely induce specialised mucosal immune responses that may correlate with greater efficacy, accelerating the deployment of clinical trials to test their ability to prevent disease and transmission in the field.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: COVID-19 Mapping and Mitigation in Schools (CoMMinS)
Funder: Medical Research Council

Abstract: This proposal will meet the urgent need for mapping and mitigation of COVID-19 in schools in light of their planned full re-opening in September 2020. Schools pose a major challenge due to features of their operation including the likelihood of cases being asymptomatic, the high number of contacts, the presence of vulnerable persons, and the potential for rapid onward transmission to family contacts of children and staff. These challenges must be weighed against the benefits to children including resuming their education, peer interaction and social development. A deeper understanding of infection history and dynamics and enhanced mitigation measures will have widespread benefit for outbreak control and future pandemic resilience. We will undertake a large-scale mapping study of prior and current COVID-19 infection in pupils and staff, including prospective testing over a 6-month period. This will dramatically enhance our understanding of infection patterns in this age group. Results will be mapped to home postcode location and linked to NHS system-wide data to highlight area-based and individual-level risk factors. We will also undertake weekly reactive testing in households with a confirmed, school-linked COVID-19 infection. To mitigate against infection transmission we will adapt evidence-based digital tools and co-create whole school implementation interventions to support positive infection control practices by staff, parents and pupils. We will co-design and develop a system to collate multiple sources of information to augment contact tracing and facilitate outbreak control. We will explore the impact of returning to school for staff and pupils' mental wellbeing, their attitudes towards actions taken to mitigate the spread of COVID-19, and potential interventions to address identified difficulties.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);4.4 POPULATION SCREENING
Health categories: INFECTION
Title: Promoting health and safety in traditional food markets to fight COVID-19 in Peru and Bolivia
Funder: Medical Research Council

Abstract: In this project we address COVID-19 control in traditional food markets, which are important hubs of community spread of COVID-19 in Peru and Bolivia and likely to play a similar role in other LMICs. Our overall aim is to prevent COVID-19 transmission in traditional food markets and we do this building on ongoing projects working with food markets of Peru and Bolivia and on recent engagements of the research team in support of COVID-19 response in these countries that have strengthened links with stakeholders. Traditional food markets are central to livelihoods in LMICs, where they play important economic and socio-cultural roles. Therefore, there is a need for risk mitigation strategies that are not only technically sound but also equitable, culturally sensitive and sustainable. We aim to design and implement such strategies through transdisciplinary collaboration that integrates local knowledge and technical expertise. Our approach includes the development and use of a risk assessment framework to identify market-specific risk mitigation strategies, the incorporation of an early detection and follow-up system to existing health services and the implementation of the risk mitigation strategies identified in parallel to a health promotion program for sellers and their families. The program will be implemented in four markets and will include periodic clinical, serological and virological follow-up. We will also develop a probabilistic model to simulate impact of changes of market operation on risk of COVID-19 infection for buyers and sellers. Central to our work are extensive interactions with all actors transversally supported by social sciences during all stages of the project. This will allow us to agree upon the activities, develop a shared vision and a participative diagnosis and ensure effective follow up and monitoring of the integrated mitigation program.We will make extensive use of visual communication and education to display the project in mass media.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Developing mass spectrometry to understand molecular mechanisms of antibacterial and antiviral drugs
Funder: Medical Research Council

Abstract: The search for new antibiotcs has become more acute as the COVID-19 pandemic has brought a surge in antimicrobial usage that is expected to drive up resistance. Here, we seek to uncover the targets and mechanisms of action of antibiotics and antivirals - aspects that remain, for many drugs, poorly understood or completely unknown. To investigate the mechanisms of action of antibiotics - both new and re-engineered - we have assembled a series of mass spectrometry-based assays, involving in vitro synthesis of bacterial cell-wall components and a clear indication of bacterial lipid flippase activity. Where targets are unknown, we will eject complexes directly from bacterial membranes, monitoring antibiotic responses over time and thereby identifying targets in situ. We also aim to identify new antibiotic targets, by establishing a mechanistic understanding of the membrane-embedded enzymes and multiprotein complexes responsible for remodelling and synthesising components of bacterial cell envelopes. Though extremely difficult to study via standard biophysical approaches, these enzymes and complexes are essential for bacterial survival; a better understanding of them will be invaluable for antibiotic targeting. For our COVID-19 research theme, we will continue our studies with existing antivirals, covering additional drugs that have shown activity in in vitro assays of virus proliferation. Probing interactions among the SARS CoV-2 main proteins, RNA and accessory factors - and, applying our expertise in membrane protein-lipid interactions, we will explore emerging COVID-19 targets, such as the two-pore cation channel in the lysosomal degradation pathway. Bringing antibacterial and antiviral studies together allows synergistic discoveries and consideration of repurposed drugs active in both scenarios, and enables us to contribute to tackling the biggest global health challenges of our time.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: The impact of COVID-19 on primary health care service provision and utilisation in Tanzania, Sierra Leone and the Democratic Republic of Congo
Funder: Medical Research Council

Abstract: The impact and implications of the COVID-19 pandemic on routine primary health care provision and utilisation in resource-poor settings is unknown. Initial reports suggest that as health care workers with comorbidities or pre-existing conditions are taken off the 'frontline', others are transferred to COVID-19 response activities, fear of COVID exposure increases absenteeism, and social distancing measures are put in place in health facilities, the capacity to provide services has been reduced. Utilisation has also been affected, potentially by users' fear of catching SARS-CoV-2 infection at health care facilities, misconceptions that services are shut, barriers to accessing health care due to fewer transport options and less disposable income during lockdowns. A reduction in primary healthcare provision could be particularly devastating in low income settings. This multidisciplinary project aims to investigate the impact that the COVID-19 pandemic is having on primary healthcare providers and users in three distinct settings in Central (Democratic Republic of the Congo), East (Tanzania) and West (Sierra Leone) Africa, by building on existing collaborative partnerships. We will conduct the following activities: 1. Data will be collected from healthcare facilities to estimate the change in the number of people seen for essential services e.g. antenatal care, outpatients, routine immunisations, family planning and HIV comprehensive care visits. 2. Qualitative interviews will be conducted with primary healthcare workers to understand barriers and facilitators for effective care provision during the COVID-19 outbreak. 3. Healthcare workers' exposure to SARS-CoV-2 will be estimated in a repeated sero-survey, using a validated serological assay. 4. Qualitative interviews will be conducted with a selection of healthcare users to understand barriers and facilitators of utilisation. 5. A set of recommendations/ key findings will be formulated together with stakeholder


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: INFECTION
Title: The DOMINO Study: Measuring and mitigating the indirect effects of COVID-19 on TB and HIV care in Indonesia
Funder: Medical Research Council

Abstract: The global health community has made urgent calls for countries to find solutions to minimising the impact of COVID-19 on programs targeting long-standing health problems such as TB and HIV (1). Indonesia, with a population of around a quarter of a billion people, currently has the highest number of COVID-19 infection cases in Southeast Asia, averaging 1000-1300 new infections each day since the 15th June and a case fatality rate of around 6.6% (2). It is also ranked third in TB burden globally (3) and one of a few countries where the number of new HIV infections is rising (4). In recent years Indonesia has strengthened its commitment to controlling these two important diseases. However, the diversion of health resources to the pandemic along with social distancing policies is creating new vulnerabilities and exacerbating existing ones for TB and HIV programs and affected populations. Our team is partnering with the Indonesian government and community organisations to conduct an observational cohort study across all TB and HIV facilities in the major cities of Bandung (N=62) and Yogyakarta (N=30) to assess clinical outcomes before and during the pandemic. We will analyse routinely collected data to measure linkage to care, retention in care and treatment outcomes along TB and HIV cascades of care. Qualitative methods will be used to explore the experiences of TB and HIV patients and their health care providers during the pandemic, including changes to treatment seeking and actions to minimise disruptions. Out-of-pocket health spending by TB and HIV patients and their families during the pandemic will be measured using structured diaries. Wider health system impacts of COVID-19 on stocks of medicines/tests and health facility funding levels will be assessed using facility records and interviews with health authorities and facility staff. Our findings will generate recommendations on how to minimise disruptions to HIV and TB services in the face of the pandemic.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: REACT-GE: Multi-omics to identify biological pathways underlying severity of SARS-CoV-2 infection.
Funder: Medical Research Council

Abstract: COVID-19 is a new infectious disease responsible for a global pandemic and presenting major knowledge gaps with respect to disease susceptibility, severity of infection and disease mechanisms. While most individuals infected with SARS-CoV-2 virus are asymptomatic or mildly affected, a minority require hospitalisation, need assisted ventilation and some progress to respiratory or other organ failure/death. The mechanisms for these differences in susceptibility and severity of disease are unknown, but are likely to encompass a combination of genetic susceptibility and gene-environment interactions that lead to downstream biochemical disturbances. We have assembled a multi-disciplinary international team of leading researchers to address these knowledge gaps by applying a multi-omics approach encompassing whole genome sequencing (WGS), proteomic, transcriptomic and metabolomic analyses to mild/asymptomatic cases. We will delineate biological pathways that are protective of or deleterious to the response to SARS-CoV-2 infection that may identify novel targets for treatment and ultimately prevention of the disease (e.g. vaccine response). The partnership between REal-time Assessment of Community Transmission (REACT) and Genomics England (REACT-GE) brings together the DHSC-funded GenOMICC programme and the community-wide viral antigen and seroprevalence surveillance (REACT) platform identifying mild/asymptomatic SARS-CoV-2 positive people in the population. We propose that c.8000 mild/asymptomatic participants are recruited through the REACT study for which we will obtain a multi-omic resource to sit alongside WGS already funded, and thus enhance the biological richness and utility of the resource for drug target discovery. Specifically we propose to undertake a series of proteomics, transcriptomics and metabolomics analyses alongside WGS to provide an unparalleled resource for multiomic phenotyping and discovery.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION