PROJECT SUMMARY Recent reports of type 2 diabetes (T2DM) as a post-acute sequela of SARS-CoV-2 infection (PASC, clinical findings lasting beyond 30 days of infection) highlight the urgent public health need to better understand and characterize the potential association between COVID-19 and T2DM. Prior studies of PASC-associated T2DM among adults living in the US have analyzed data from populations with limited racial/ethnic diversity, making the results difficult to generalize to Black and Hispanic communities that experience disproportionately higher rates of SARS-CoV-2 infection, COVID-19-related morbidity and mortality, and T2DM in the US. To advance our understanding of T2DM risk after SARS-CoV-2 infection in racial and ethnic minority communities, we will conduct a retrospective cohort study using the OneFlorida+ Data Trust, a Clinical Research Network (CRN) within the National Patient-Centered Clinical Research Network (PCORnet) that contains patient-level electronic health record (EHR) data for a diverse population of 19.2 million Americans seeking care in all major metropolitan regions in Florida (the state with the 3rd highest number of COVID cases in the US) as well as Atlanta, GA and Birmingham, AL. The association between SARS-CoV-2 infection and incident T2DM has yet to be empirically quantified by race and/or ethnicity using rigorous methods and relevant variables (social vulnerability and individual susceptibility factors) for diverse populations, despite the markedly higher rates of COVID-19 and T2DM in minority communities. We will employ a rigorous analytic approach that utilizes high- quality data available for both individual susceptibility and social vulnerability factors in the OneFlorida+ Data Trust, a dataset that includes large proportions of minority groups (24% Hispanic, 18% Black), to address this critical gap in knowledge. In addition to standard EHR data such as diagnosis/procedure codes, laboratory values, medications, patient demographics, and vital signs, the OneFlorida+ Data Trust includes linkages to exposome data on the natural, built, and social environments. Additional strengths of the OneFlorida+ Data Trust for this project include availability of validated computable phenotypes (CPs) for diabetes to reduce the chance of outcome misclassification; differentiation of healthcare encounter types; larger proportions of young adults and women than prior studies of PASC-associated T2DM; diverse payer sources; and the capacity to link patient records across OneFlorida+ Data Trust contributing sites. Our specific aims are (1) to assess racial/ethnic differences in PASC-associated T2DM incidence in a retrospective cohort using the OneFlorida+ Data Trust and (2) to compare changes in cardiometabolic risk factors following SARS-CoV-2 infection by race/ethnicity in a retrospective cohort using the OneFlorida+ Data Trust. This study will fill critical knowledge gaps in the potential association between COVID-19 and new-...