eMERGE SARS-CoV-2 Supplement: Pulmonary, renal, and inflammatory components

Abstract: As of May 4, 2020, more than 3.5M cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and 250,000 deaths have been reported worldwide, with more than 1.2M cases and over 70,000 deaths in the United States. The severity of infection varies from no symptoms to respiratory failure and death. Genetic factors appear to underlie some interindividual variability in SARS-CoV-2 infection outcomes. Part of this heritability may be associated with host immune response, as lymphocyte measures at hospital admission predict disease severity. It may be may also be important to understand whether an individual's underlying or "baseline" lymphocyte count is a risk factor for infection and/or severe disease; a multiancestrypolygenic risk score for lymphocytes will be tested for its prediction of COVID-19 severity to address this hypothesis. This supplemental project will improve 1) standardization of electronic health record phenotyping of the pulmonary and renal complications of COVID-19 to improve transferability across sites; and 2) our understanding of host genetic risk factors playing a role in disease severity. We propose to work within the aimsof eMERGE4 to study interindividual variability in COVID-19 severity by developing transferable EHRphenotyping of pulmonary and renal outcomes, evaluating ABO blood group association and GWAS contrasting those COVID-19 patients with respiratory failure (inpatient) with those who remained outpatients, and evaluating whether a multi-ancestry PRS for lymphocytes predicts COVID severity. This project can stand on its own, but we will gain power by pooling data across eMERGE and benefit by testing EHR phenotyping at multiple sites to assure transferability. We will also broadly share any data.