The External Exposome and COVID-19 Severity

PROJECT Summary: The 2019 novel coronavirus disease (COVID-19) is a global pandemic with severe medical and socioeconomicconsequences. Young adults without any underlying health conditions can still develop severe COVID-19disease, and there are racial and ethnic disparities in COVID-19 hospitalization and mortality rates whichcannot be explained by age and underlying health conditions alone. Risk factors of severe COVID-19 beyondolder age and underlying health conditions are large unknown. There are large overlaps between the currentlyknown risk factors of severe COVID-19 and the health conditions that are affected by environmentalexposures, and emerging evidence suggested that long-term environmental exposures may be importantdeterminants of COVID-19 severity. Traditional environmental epidemiological studies usually examineenvironmental factors separately without considering "the totality of the external environment". Such studiesare not only time consuming as they examine individual exposures separately, but more importantly, cannotaccount for confounding by co-exposures. The external exposome is an ideal framework to identify novelexposures associated with severe COVID-19 as it can systematically and efficiently screen thousands ofenvironmental exposures. In this project, we will leverage a unique real-world data (RWD) resource -OneFlorida - a large repository of linked electronic health records (EHR), claims and vital statistics data,covering more than 60% of Floridians, contributing to the national Patient-Centered Clinical Research Network(PCORnet). Building on our prior work on the external exposome, we will expand our existing externalexposome database to include additional factors that may impact COVID-19 outcomes through a systematicanalysis of literature and resources. We aim to (1) develop phenotyping algorithms for identifying a COVID-19cohort and their severity and extracting associated individual-level risk factors from the OneFlorida real-worlddata, and (2) identify external exposome factors associated with severe COVID-19, examine how the externalexposome contributes to racial and ethnic disparities in severe COVID-19, and build predictive models ofsevere COVID-19 with external exposome factors. This study will fill important knowledge gaps by providingtimely information to understand how environmental exposures may impact COVID-19 severity that willimprove identifications of high-risk COVID-19 patients and inform the design of future precision interventions.Our approach and initial results for Florida can (1) be readily scaled up to a multi-state study through PCORnetand (2) answer other novel questions such as the external exposome's contribution to geographic disparities inCOVID-19 outcomes.