REACT Long COVID (REACT-LC)

Some people with COVID-19 experience symptoms for several weeks or months (Long COVID), while others have a short illness or no symptoms. We have very little understanding of why this happens. Most research on Long COVID has been with hospitalised patients. Our study will involve people in the community who have taken part in the REACT study of the virus that causes COVID-19. Over 30,000 people from REACT have had positive test results and they, plus a sample of 90,000 who tested negative, will be invited to take part in the new study. These 120,000 people will be sent a survey about their health, symptoms and experiences since the test; we will also link to health records. Participants with Long COVID will be asked to join a panel to provide regular updates on their symptoms; 60 will be invited for in-depth interview. We will repeat the survey of the 120,000 after 18 months to track symptoms and their health. We will work closely with a panel of public advisers including people with Long COVID to develop a set of patient-reported outcomes that reflect the symptoms that are most important. We will also invite up to 8,000 people with positive tests, including at least 4,000 with Long COVID, to an assessment centre for health tests and samples to test for genetic and other biological markers. Around 2,000 will attend a follow-up visit after 4-6 months for repeated measurements and samples. The data from these studies will be analysed to find factors affecting why some people get Long COVID and others don’t. The biological studies will help us understand mechanisms causing persistent symptoms and may point to possible treatments. Through the surveys and work with participants we will understand why some people are more vulnerable and how best to support them.

This COVID-19 Long COVID award is jointly funded (50:50) between UKRI/Medical Research Council and the National Institute for Health Research. The figure displayed is the UKRI/MRC amount only, each partner is contributing equally towards the project so the Total Fund Amount is £5,436,399.

The REACT-Long COVID (REACT-LC) programme aims to characterise the genetic, biological, social and environmental signatures and pathways, and their inter-relationships, that underpin progression to Long COVID, and to understand the natural history and long-term sequelae post-SARS-CoV-2 infection. To identify people with persistent symptoms who have not been hospitalised, we will use a sampling frame generated through repeated random population surveys of SARS-CoV-2 prevalence in the community, the REACT programme, which includes >1.5 million individuals with documented SARS-CoV-2 status (RTPCRor lateral flow test), including >30,000 with positive tests, 90% of whom have consented to be re-contacted and 85% to data linkage. The research is to be delivered through five integrated work packages (WPs). WP1 will describe variations in experience of Long COVID and develop patient reported outcomes (PROMS) in consultation with expert collaborators and through our patient and public partners. We will use online focus groups, discussion forums, individual interviews, and surveys on the VOICEGlobal platform, and recruit a panel of people with Long COVID to provide input on their symptoms and experience. In WP2 we will carry out detailed clinical phenotyping on 8,000 people (4,000 with Long COVID); 2,000 will have repeat measures at 4-6 months including 400 for T-cell function. The WP2 samples will be used in WP3 which includes multi-omic analysis, brain and inflammatory biomarkers. WP4 will use data from surveys sent to 30,000 test-positive and 90,000 test-negative on RTPCR/lateral flow in REACT, plus linked health data, to explore the social and environmental determinants of Long COVID and its long-term sequelae. WP5 is the data analysis and integration to identify genetic, biological, social and environmental determinants of Long COVID. We aim to identify key biomarkers and biological pathways underlying Long COVID and possible drug targets, as well as inequalities and social determinants of variations in outcome.