The MRC Centre for Environment and Health is contributing to the global research effort to tackle the COVID-19 pandemic. Below is a list of current and planned Covid-19 research studies and other activities by MRC Centre teams.The MRC Centre for Environment and Health is contributing to the global research effort to tackle the COVID-19 pandemic. Below is a list of current and planned Covid-19 research studies and other activities by MRC Centre teams.
The REACT programme is a large-scale assessment of COVID-19 home testing, to evaluate different testing assays and inform the future deployment of self-testing, and to provide estimate levels of SARS-CoV-2 infection in the population (including asymptomatic cases). The programme comprises two main arms: - REACT 1: a rapid, large-scale study of SARS-CoV-2 antigen prevalence in England, involving the collection and analysis of swab samples for a large sample of the population (100,000 randomly selected people from 315 local authorities across England) to identify rates of active SARS-CoV-2 infection. - REACT 2: is the largest COVID-19 surveillance study undertaken in England examining the prevalence of SARS-CoV-2 antibodies in the community. It consists of a series of studies evaluating the accuracy, usability and acceptability of different home-use, self-administered Lateral Flow Tests (LFTs) to detect COVID-19 antibodies and prior infection, together with a large-scale study (up to 200,000 randomly selected members of the public in England) to quantify the cumulative community seroprevalence since the beginning of the SARS-CoV-2 epidemic and characterise geographical and socioeconomic variations. Publications: Flower B, Brown JC, Simmons B, et al. Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey. Thorax. Published Online First: 12 August 2020. doi: 10.1136/thoraxjnl-2020-215732 Graham NSN, Junghans C, Downes R, et al. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes. J Infect. 2020;81(3):411-419. doi:10.1016/j.jinf.2020.05.073 Atchison C, Pristerà P, Cooper E, et al. Usability and acceptability of home-based self-testing for SARS-CoV-2 antibodies for population surveillance [published online ahead of print, 2020 Aug 12]. Clin Infect Dis. 2020;ciaa1178. Ward H, Atchison CJ, Whitaker M, et al. Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults. [Preprint] medRxiv - doi:10.1101/2020.08.12.20173690 Riley S, Ainslie KEC, Eales O, et al. Transient dynamics of SARS-CoV-2 as England exited national lockdown. [Preprint] medRxiv - doi: 10.1101/2020.08.05.20169078 Riley S, Ainslie KEC, Eales O, et al. Community prevalence of SARS-CoV-2 virus in England during May 2020: REACT study. [Preprint] medRxiv - doi:10.1101/2020.07.10.20150524
Siemens Healthineers markets a range of tests supporting the diagnosis and management of COVID-19. This industrial partner is interested in collaborating with the REACT team to assess the performance of its antibody tests and to evaluate the extent to which unsupervised subjects can self-collect samples to support testing.
REACT-GE: Multi-omics to identify biological pathways underlying severity of SARS-CoV-2 infection - PI Prof Paul Elliott
This study aims to address some of the major gaps in our understanding of SARS-CoV-2 infection and disease, in particular with respect to differences in disease susceptibility, severity of infection and disease mechanisms. We will apply a multi-omics approach - encompassing whole genome sequencing, proteomic, transcriptomic and metabolomic analyses - to mild/asymptomatic cases, to identify biological pathways that are protective of or deleterious to the response to SARS-CoV-2 infection. In a partnership between the DHSC-funded GenOMICC programme (led by Genomics England) and the REACT programme, we propose to recruit c.8000 mild/asymptomatic REACT participants for which we will obtain a multi-omic profile to sit alongside the whole genome sequencing already funded, creating an unparalleled resource for identifying novel targets for disease prevention or drug discovery.
SCAMP-COVID19: a school-based cohort study of COVID-19 secondary impacts on mental health - PI Prof. Mireille Toledano
This study aims to look at the prevalence of COVID 19 symptoms and serology amongst a large adolescent cohort SCAMP (Study of Cognition Adolescents and Mobile Phones), and their households. The data will be used to: - investigate the association between COVID-19 and ethnicity, socio-demographic and lifestyle factors, to further our understanding of potential susceptibility of BAME groups and identify modifiable risk factors to reduce morbidity and mortality; - evaluate changes in mental health, physical activity, sleep, digital screen time use during lockdown and beyond in the SCAMP adolescent cohort; - feed into real time modelling work ongoing at Imperial to inform policy response.
Recent studies suggested a link between long-term exposure to air-pollution and COVID-19 mortality. However, due to their ecological design, based on large spatial units, they neglect the strong localised air-pollution patterns, and potentially lead to inadequate confounding adjustment. We investigated the effect of long-term exposure to NO2 and PM2.5 on COVID-19 deaths up to June 30, 2020 in England using high geographical resolution. Publications: Konstantinoudis G, Padellini T, Bennett JE, et al. Long-term exposure to air-pollution and COVID-19 mortality in England: a hierarchical spatial analysis. [Preprint] medRxiv - doi:10.1101/2020.08.10.20171421
Estimating weekly excess mortality at sub-national level in Italy during the COVID-19 pandemic - PI Prof. Marta Blangiardo
This is the first subnational study on excess mortality during the COVID-19 pandemic in Italy, one of the worst-hit countries. We predicted the weekly mortality rates at municipality level for 2020 based on the modelled spatio-temporal trends (i.e. in the absence of the pandemic) and estimated the excess mortality and the uncertainty surrounding it. This study showed strong evidence of excess mortality for Northern Italy from the end of February 2020, with marked geographical spatio-temporal differences at municipality level. After discounting for the number of COVID-19-confirmed deaths, 10,197 (9,264 to 11,037) excess deaths were registered in the Lombardy region alone, with the city of Bergamo showing the largest percent excess (88.9% - 81.9% to 95.2%) at the peak of the pandemic. Publications: Estimating weekly excess mortality at sub-national level in Italy during the COVID-19 pandemic. Blangiardo M, Cameletti M, Pirani M, et al. Manuscript under review. medRxiv - doi.org/10.1101/2020.06.08.20125211
In this collaborative study with the University of Toronto (Canada), we investigate whether long-term average exposure to air pollution (PM2.5 and NO2) increases the risk of COVID-19 infection in Canada, England, Italy and the United States. Data are collected for areal units in each country and the spatial areal unit design is employed to produce estimates of health effects on a population level. We estimate a population attributable fraction for each country, then derive from these a combined global estimate of exposure health effects. Paper in preparation.
This project, in collaboration with UCL and the Met Office, aims to study the exacerbating effect of air pollution on COVID-19 health outcomes by: (1) fusing a unique set of updated Met Office observations and model outputs to fit a novel dose-response statistical model for the UK at a local level of average population of 1,500 individuals; (2) creating new probabilistic forecasts of air pollution at this local scale over the next 15 days. This is made possible thanks to access to both the Met Office high performance computing and the Met Office state-of-the-art air quality numerical model. These forecasts will enable more accurate modelling of the impact of future air quality on health and healthcare systems, supporting decision-makers and public health officials in implementing measures tailored to predicted pollution levels.
Risk factors for positive and negative COVID-19 tests using UK biobank data - PI Prof. Marc Chadeau-Hyam
Analysis of UK Biobank data identifying risk factors for testing positive or negative for SARS-CoV-2 infection up to 18 May 2020, as well as those discriminating test positive vs test negative individuals using a test negative design approach. Publications: Chadeau-Hyam M, Bodinier B, Elliott J, et al. Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK biobank data [published online ahead of print, 2020 Aug 20]. Int J Epidemiol. 2020. PMID: 32814959; DOI: 10.1093/ije/dyaa134. Elliott J, Bodinier B, Delpierre C, et al. COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors. Submitted.
Studying the cardiovascular complications related to SARS-CoV-2 infection through the Covidity cohort consortium as well as NHS digital datasets
Mendelian Randomization (MR) to identify likely causal risk factors for of COVID-19 clinical outcomes and to investigate side-effect of hypertensive drugs - Dr Verena Zuber
Based on first genome-wide association studies of COVID-19 severity we can use the MR paradigm to identify likely causal cardiometabolic risk factors for COVID-19 severity . We have also looked at how cardiometabolic risk factors impact genetic predisposition to increased angiotensin-converting enzyme (ACE) expression and have provided genetic evidence that ACE inhibitor antihypertensive drugs may not affect lung ACE2 and TMPRSS2 expression . These findings do not support a change in ACE inhibitor medication use without clinical justificationMark PJ, Gkatzionis A, Walker V, et al. Cardiometabolic traits, sepsis and severe covid-19 with respiratory failure: a Mendelian randomization investigation. [In Press] medRxiv: 2020.06.18.20134676; doi:10.1101/2020.06.18.20134676 Publications: Gill D, Arvanitis M, Carter P, et al. ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study. [In Press] medRxiv: medRxiv 2020.04.10.20059121; doi: 10.1101/2020.04.10.20059121
COVIRNA will complete and deploy a prognostic system based on cardiovascular biomarkers, in particular long non-coding RNA, of COVID-19 clinical outcomes combined with digital tools and artificial intelligence analytics (i.e. prediction model). The aim is to identify COVID-19 patients at risk of developing cardiovascular events leading to death, which would allow improved surveillance and care.
High time resolution aerosol size distribution measurements in an ICU ward at Medway Hospital in association with Dr Rahuldeb Sarkar, Consultant in Respiratory Medicine & Critical Care Medway NHS Foundation Trust. - Measuring aerosol generation from patient under different ventilation methodologies and different procedures - Aim to assess aerosol exposure of staff working in close proximity to COVID patients - Paper describing early results submitted to the British Journal of Anaesthesia.
The change in emissions associated with the pandemic provides a ‘real world’ opportunity to assess emission reduction impacts on population exposure and atmospheric chemistry at a time when there is concerted policy effort to reduce the UK’s air pollution health burden. Defra’s Air Quality Evidence Group issued a call for evidence and ERG members are undertaking analyses to inform this and prepare potential future funding applications: - Spatial and temporal analysis of LAQN monitoring sites to establish changes in concentration between pre lockdown and lockdown periods; including accounting for the effects of changes to meteorology and dispersion to estimate emission changes. - Estimation of the changes to the toxic mixture of air pollutants, and in particular the combined toxicity of different pollutants. - Quantifying changes to personal exposure of people in London, indoors and outdoors, including school children, professional drivers, medics and tube users. - This is also an ideal opportunity to study the air pollution impacts of a world working towards 'net-zero' CO2 emissions, improving our understanding of model uncertainties and the reliability of policy analysis and air pollution predictions for net zero scenarios. - Initial analysis undertaken and reported to Defra’s Air Quality Expert Group. More detailed analytical project in planning.
Children’s Health in London and Luton (CHILL): impact of London’s Ultra Low Emission Zone on brain development in schoolchildren - PI Dr Ian Mudway
This study within the CHILL cohort aims to examine the impact of Sars-Cov-2 infection / air pollution changes (both policy and lockdown driven) on the cognitive development of children. We trialled cognitive testing in tis cohort last year and the proposal will expand on this work and establish more formal links with the Born in Bradford group, whose methodology is used.
The COVID 19 pandemic: a study of air pollution exposure, behaviour and health in London - PI Dr Sean Beevers
The Covid-19 lockdown is the largest ‘natural experiment’ of global emissions reductions of a generation. The aim of this study is to assess the change in personal exposure of the whole London population to PM2.5 and NO2 brought about by both the change in indoor, in-vehicle and outdoor concentrations, as a consequence of the Covid-19 lockdown, and due to behaviour change such as spending more time at home and changing mode of transport. London has a diverse population so we will undertake this analysis for different population subgroups, by age, focusing on the vulnerable such as the over 70s, gender and ethnicity (e.g. BAME). We will assess the health impacts of past long-term exposures, changes in exposure during the pandemic interventions and their interactions with Covid-19 transmission and mortality.
Is air pollution exposure indoors, outdoors and whilst travelling disproportionately affecting those that are vulnerable to COVID-19 - PI Dr Sean Beevers
The impact of the COVID-19 has disproportionately affected those with pre-existing disease, including those with diabetes, the obese, as well as old people, males and Black and Asian ethnic groups. Air pollution has been cited as a potential additional risk factor for COVID-19 disease. This study aims to significantly improve our understanding of the exposure to air pollution indoors and outdoors, of different vulnerable sub-populations in London during the COVID-19 lockdown. We will use the novel NERC-funded London Hybrid Exposure Model (LHEM) which is unique in the UK, and in analysis for Defra's Air Quality Expert Group has already given some important insights into the potential exposures during the COVID-19 lockdown period. During the COVID-19 lockdown and subsequent easing of the restrictions, we will assess the change in personal exposure of all Londoners to PM2.5, NO2 and O3, split by age, gender, ethnicity, socioeconomic status, and by occupation, such as professional drivers, tube users, medical staff and children. Improving our understanding of the sources of exposure will lead to policy advice on exposure reduction and provide a unique exposure dataset that will allow epidemiologists to better assess whether air pollution is a risk factor for COVID-19.
Measuring population-level health & activity in a global pandemic by wastewater-based epidemiology - PI Dr Leon Barron
Measuring SARS-CoV-2 and pharmaceuticals in urban wastewater using mass spectrometry, to accurately monitor large population activity in near-real time
Via COMEAP, involved in commenting on papers on air pollution and COVID19 published by others. Via COMEAP, in discussions with PHE and ONS on possible links between air pollution and Covid-19; ONS report published in early August.