NIHRDataInsights/HRCSData huggingface dataset:
Title: Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour.
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 is set to become a global pandemic. Near real time information is needed to inform NHS planning and public health response. This includes community incidence (regardless of seeking care), risk factors for disease, clinical symptoms, case hospitalisation and mortality ratios, asymptomatic viral shedding, asymptomatic infection, household transmission risk and population behaviours during periods of wellness and illness (including social contact and movement, respiratory hygiene and health seeking behaviours). This information can only be gathered accurately through large scale community studies. Our experience of the MRC/Wellcome FluWatch study and ESRC BugWatch study allows us to rapidly establish two six-month national household cohorts (April-September 2020) and (October 2020-March 2021) of 25,000 individuals each (2,500 in each region of England and Wales) for online symptom and behaviour reporting and optional use of an app allowing their mobile phones to be used as GPS trackers enabling secure transfer and analysis of detailed movement patterns. Two sub-cohorts (10,000 individuals each) will also self-swab when ill for detection of COVID-19 and other circulating viruses. We will also conduct a London based study (200 households) following household contacts of COVID-19 cases for 28 days with daily symptom reporting, regular swabbing and baseline and follow up serology to investigate household transmission and asymptomatic infection and virus shedding. We will use data from Virus Watch to train whole population prediction models based on social media and search engine data and develop spatiotemporal models. Findings will be rapidly disseminated via online dashboards informing the public and decision makers.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: INFECTION
Title: Understanding Chinese government containment measures and their societal impacts
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The WHO database of research on COVID-19 contains 589 studies, the majority of which are on virology, epidemiology and clinical management. Only two (Kavanagh 2020; McCloskey et al. 2020); discuss (but do not report research on) wider governance issues. Yet the Chinese Communist Party leadership’s response to the epidemic has been comprehensive well beyond clinical management. It has set up high level coordinating mechanisms across government ministries that have issued hundreds of policy documents setting out containment measures. In this way it has mobilized Party and government organizations across (for example) social care, transport, and policing that reach through local governments into every work place and community. It has used TV, print and social media to communicate measures with the public, while the public have used social media as well as self-organization to respond to measures whether by complaining and criticizing or by supporting and complementing government measures. This project will: systematically compile a database of policy documents (available from Chinese government websites) that set out containment measures as they are evolving through the epidemic; use text and computational analysis of newspapers and social media databases (Weibo Scope and WeChat Scope) we will purchase; and conduct local fieldwork (qualitative interviews) to analyse the societal impacts in urban and rural areas and responses on social media and (focussing on companies, and NGOs and citizens) in four carefully chosen localities (Hubei, Beijing, Guangdong and Anhui). The result will be important and novel resources mapping and assessing Chinese containment measures and their societal impacts, that will be communicated and updated regularly for national and international governments and organizations attempting to tackle COVID-19 around the world.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION
Title: Estimating severity from multiple data sources using Bayesian evidence synthesis
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. In preparing for a possible COVID-19 pandemic, estimates of severity, in particular of both the numbers of infections occurring at different levels of severity and the infection- and case-severity risks, are crucial to understand and predict the burden and impact of the epidemic on healthcare services. Such estimates are most importantly needed by age and risk group (e.g. defined by co-morbidities) strata, although in the early stages of an epidemic, strata-specific information is rarely available. No single dataset can provide enough information on its own to estimate severity, but estimation is feasible by synthesising multiple datasets, such as: line-listing data from first few hundred type studies; surveillance data including case counts, numbers accessing healthcare, and numbers of deaths; cohort studies; and household studies. Such a synthesis needs to account for biases inherent in each data source, including differential ascertainment by severity level; and to account for the incomplete nature of the data, which, collected in real time, are typically affected by censoring of final outcomes (recovery/hospital discharge or death). We propose to make the best use of both individual- and aggregate-level data that will become available, by using a combination of survival analysis techniques (e.g. curerate mixture or competing risks models) and Bayesian evidence synthesis in a single analysis to estimate severity in real time, as data accumulate over the course of the epidemic, and once the epidemic is over.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Early Assessment of COVID-19 epidemiology and Vaccine/anti-viral Effectiveness (EAVE II)
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. Some additional funds were added in January 2022 to be paid by NIHR only. EAVE (Early Estimation of vaccine and Anti-Viral Effectiveness) was a NIHR-funded project on pandemic influenza, which created a Scotland-wide cohort of 227,000 individuals recruited from 40 general practices together with stored serology samples from 1,000 individuals. EAVE established a national electronic cohort though linking health data sets from general practice, prescribing, hospitalisations and virology testing using the unique Community Health Identification (CHI) number for residents of Scotland. We plan to repurpose and expand this cohort to collect electronic data from 1.2m individuals living in Scotland to study COVID-19. We will augment the cohort by collecting and storing residual sera samples and by sequencing virus from patient specimens. Both of these, are being taken as part of routine care from a sample of these individuals. We will track the progress of the COVID-19 epidemic in near real-time using the EAVE II cohort. We will be able to model the full course of the epidemic from genome sequence data. Once a serological test becomes available we will be able to refine this model and provide precise estimates of the attack rates in different sub-populations, and accompanying hospitalisation and fatality rates. EAVE II will help to identify the clinical features of the epidemic and, in due course, provide estimates of the effectiveness of any vaccines and anti-viral therapies deployed. Ethical and Privacy Committee approval has previously been given for the EAVE study and we anticipate the same approvals will readily be obtained for this follow-on study.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: INFECTION
Title: nCoV: Serological detection of past SARS-CoV-2 infection by non-invasive sampling for field epidemiology and quantitative antibody detection
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The escalating numbers of affected individuals in China and the potential for importation of this infection to the UK during the pre-symptomatic and potentially infectious stage renders containment problematic. Acute diagnostic PCR is of short duration usefulness in identifying those recovered from the infection. The pattern of disease is clinically diffuse rendering identification of previous infections through clinical history very difficult. Here we describe the commitment of an exceptional and highly capable scientific group who, including the PI, have previously developed specific, sensitive serology for Ebola, Zika and Lassa. The Ebola tests were instrumental in the identification of seropositive persons who had recovered silently from Ebola and characterising their antibody response. Following the same methodology for SARS-CoV-2 will allow specific detection of antibody rather than placing reliance on SARS serological assays, permitting measurement of the penetration of this infection into any susceptible population. A test format will also be developed for the non-invasive sampling of oral fluid for G and M class antibody. Recombinant envelope proteins S1 and S2 and nucleoprotein will allow the sensitive detection of antibody. Our assays, also adaptable for Point of Care and diagnostic use, will be rendered specific by described methods for conjugate quenching previously developed by the group for Zika(1). Having serology which is diagnostically important for public health, herd immunity measures will also enable establishing WHO international standards. Measurement of neutralising antibody will be important for vaccine studies and characterisation of convalescent plasma(2).


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE)
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 disproportionately affects people ≥ 50 years old with comorbidities and those ≥ 65 years old. No specific treatment has yet been proven in rigorous clinical trials to be effective against COVID-19. Most clinical trials are hospital-based. Yet, most cases are managed in the community, so interventions proven to be effective are urgently in primary care that prevent hospitalisation and speed recovery. PRINCIPLE will be a Phase III, platform, response-adaptive, open-label randomised controlled trial in primary care. The platform trial will operate under a master protocol that allows the addition or replacement of further interventions. Outcome data will be analysed as the trial is in progress: if evidence emerges that one arm is more effective, we might be able to allocate more people to that arm. PRINCIPLE will, in the first instance, evaluate usual care plus hydroxychloroquine 200mg twice a day for 7 days. This drug is already in wide use, but not for this indication. The comparator will be usual care without a study drug. Eligible patients will be aged ≥50-64 years with a defined comorbidity, and patients aged ≥65 with or without comorbidity presenting within 7 days since onset of symptoms with a new continuous cough and/or high temperature during time of prevalent COVID-19 infection. Approximately 3000 eligible participants will need to be randomised in the first instance in order to determine whether the first drug we plan to evaluate is more effective than usual care alone in preventing hospital admission and/or death in people with suspected COVID-19.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Healthcare Workers: an in depth virological analysis and behavioural study during the outbreak
Funder: Medical Research Council

Abstract: This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The further spread of the novel coronavirus SARS-CoV-2 outside China, causing coronavirus disease (COVID-19) globally has led to an outbreak that WHO announced 12 March 2020 as a pandemic. The role of Healthcare Workers (HCWs) in managing the outbreak is critical, while working in a setting where they may be inadvertently exposed to SARS-CoV-2, and WHO has prioritised research on how best to protect them from infection and disease. The similar “Public Health Emergencies of International Concern” caused by Zika and Ebola highlighted another important aspect: the need to integrate social sciences research into the outbreak response and to address ethical questions around studies and data sharing, in this context involving HCWs. With our proposal, we aim to integrate three key priorities in a unique way. We will leverage existing funding and our experience within the ICONIC study, funded by the Wellcome Trust/DoH (2014-18). We propose an in-depth analysis of risk of infection with SARS-CoV-2 in HCWs including longitudinal sampling, tracking of movement and studies of behaviours and influences on them (capability, opportunity and motivation). We will perform a virological analysis of infected patients with serial samples to construct a detailed analysis of transmission clusters. The latter will provide valuable clinical data on virus shedding. Finally, we propose to address the ethical questions around the use of apps and wearables, data sharing and conducting studies during an outbreak to produce a set of definitive recommendations for policy makers.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION
Title: COVID-19 therapeutics and beyond: An HTS to identify inhibitors of SARS-CoV-2 nsp12 and starting points for other Coronavirus inhibitors
Funder: Medical Research Council

Abstract: In the face of rapidly emerging viral pandemics, the normal commercial approach to antiviral translational research will not produce therapeutics in a timely manner. Consequently, there is an urgent need to prepare a strategic resource, openly available, to stimulate research into new antivirals for emerging viruses and, in an emergency situation, to provide compounds for expedited preclinical and human testing. Identification of collections of potent inhibitors of essential viral mechanisms within a virus family provides an excellent starting point for this accelerated transition to preclinical toxicity studies. Ultimately, we envisage libraries of ‘poised’ anti-coronavirus compounds would enable future responses to emerging pandemics as well as targeting SARS-CoV-2. We believe high throughput screening of a well-curated library enables this, with a focus on identification of robust chemical templates suitable for optimisation. We propose an HTS to identify non-nucleoside small molecules (mwt 200-450 Da) that inhibit the nsp12, the SARS-CoV-2 RdRp. Dependent upon the activity of our molecules, we will test our compounds against other coronavirus replicon systems or infectious virus. The coronavirus polymerase is a druggable antiviral target, conserved across the viral family. SARS-CoV RdRp and SARS-CoV-2 RdRp share a remarkable 96% identity. Morse et al (2020) comment that ‘efforts towards drugging coronavirus in a RdRp manner should provide a basis not only to develop therapeutics for 2019-nCoV, but could provide broad-spectrum antivirals useful for future CoV outbreaks’. To that end we expect that classes of inhibitors identified by this proposal will have application across the coronavirus family.


Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: INFECTION
Title: Tackling Emerging Co-Infections
Funder: Medical Research Council

Abstract: Humans are continuously exposed to multiple pathogens yet, with the exception of a few well defined coinfection scenarios (HIV and tuberculosis for example), relatively little is known about the impact of co-infections on morbidity and mortality. There is growing evidence indicating that co-infections are common, exacerbate disease severity and can considerably worsen outcome (Influenza or COVID-19 associated Aspergillus infection for example). Co-infections with drug-resistant pathogens have shown to add another layer of complexity with high case-fatality rates. Our aim is to integrate and exploit the expertise of four Centres that are tackling the major pathogen groups [viruses, bacteria, fungi and parasites] to promote UK-wide research on the pathophysiological impact and mechanistic basis of disease in co-infections.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: The Influenza Virus Toolkit: a reagent sharing resource for influenza research
Funder: Medical Research Council

Abstract: The aim of this proposal is to develop an influenza virus reagent resource, an outward-facing national asset for the long-term storage and redistribution of influenza virology reagents. Influenza viruses are one of the leading global causes of respiratory illness and have been the subject of intensive research over decades. This has created a highly active but dispersed research environment. A wealth of non-commercial reagents exists, but they are challenging to identify and time-consuming to obtain, and requests for them create significant administrative and archiving burdens for the originating groups. We will address this by creating the Influenza Virus Toolkit, a resource-sharing initiative modelled after our recently developed Coronavirus Toolkit. This will build on the established MRC Reagents and Services framework and the CVR Reagent Repository to provide a sustainable, long-term framework for the archiving and redistribution of reagents for influenza virus research, for academics and industry, in the UK and overseas. This project will mobilise resources in the extremely active field of influenza virology, in particular catalysing resource sharing from the current MRC portfolio of virology research. It will foster open-science and a culture of collaboration among influenza researchers. Importantly, it will also create a key resource for the rapid provision of research reagents during the next influenza pandemic.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Interim support for ISARIC4C Clinical Characterisation Protocol (CCP) activation for acute severe hepatitis in children of unknown cause
Funder: Medical Research Council

Abstract: A series of cases of severe hepatitis in young children of unknow cause were recognised in Central Scotland in March 2022. As of 11 May 2022, there have been 176 such cases across the UK, predominantly in children under 5 years old. The aetiology is unknown but an infection or co-infection is a strong possibility and preliminary data from ISARIC CCP work suggests that co-infection with adenovirus 41F and an adeno-associated virus 2 (AAV2) may be responsible. The CCP is a “sleeping” research protocol, established nationwide in 2013 to provide a rapid research response to new outbreaks and exposures of public health interest. It is managed by a broad consortium of experts with a proven track record of high-quality outbreak research. In partnership with medical and scientific experts and public health agencies including UKHSA and PHS, we responded immediately to this outbreak by using the existing ISARIC CCP-UK.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Addressing TBMM
Funder: Medical Research Council

Abstract: Background: TB often coexists with other conditions, including mental disorders and chronic communicable and non-communicable diseases, e.g. HIV/AIDS, diabetes and depression. This 'TB multimorbidity' can be explained by a clustering of common social and behavioural determinants, impaired immunity and drug interactions. The bi-directional, adverse interactions between TB and other conditions worsen treatment adherence and patient outcomes. However, healthcare services, including TB programmes, typically focus on single conditions, missing opportunities to integrate prevention, screening and management of multimorbid disorders and thereby to improve outcomes and efficiency of healthcare. Aims: Our long-term goal is to improve life expectancy, health outcomes and quality of life in people with TB multimorbidity, and generate learning that could be used to improve the care of multimorbidity more widely. Methods: We will define clusters of conditions contributing to disease burden associated with TB multimorbidity and identify candidate interventions to address them. In a future programme, we will develop and evaluate an integrated package of care that can help prevent, screen and manage multimorbid chronic conditions in people with TB. In this first (seed-funding) stage, we will conduct literature reviews and secondary analysis of World Health Survey data to identify TB multimorbidity clusters, risk factors, outcomes and candidate interventions to prevent, screen and treat these conditions. We will also explore other data sources on TB multimorbidity. A global Network will help agree the target clusters, share knowledge of data sources, help collate interventions for a TB multimorbidity intervention package and support dissemination. We will grow capacity in research, leadership and finance governance. We build on previous work in TB, HIV, mental health and NCD and established collaborations in mental and physical multimorbidity and TB and lung health.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION