REACT-GE: Multi-omics to identify biological pathways underlying severity of SARS-CoV-2 infection.

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 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.