Scanning the Medical Phenome to Identify New Medical Diagnoses After Recovery From COVID-19 in a US Cohort

Abstract

Background: COVID-19 survivors are at risk for long-term health effects, but population-level data remain limited. High-throughput methods to efficiently identify new medical problems among COVID-19 survivors using large electronic health record (EHR) databases could improve surveillance of COVID-19’s long-term consequences.Methods: Retrospective cohort study using a research-enabled EHR registry of all adults who underwent SARS-CoV-2 testing at Vanderbilt University Medical Center from March 5, 2020 to May 1, 2021. We extracted every new diagnosis code entered into the EHR following recovery from infection or after an equivalent time period for patients who tested negative, and assessed development of over 1,000 disease outcomes using a phenome-wide association study (PheWAS) approach.Findings: We included 148,710 adults tested for SARS-CoV-2 , of which 24,203 (16·3%) tested positive. Median follow-up was 275 days (IQR 198–364). After correction for multiple testing (p ≤ 4·89×10-5), COVID-19 survivors had increased risk for 24 clinical phenotypes during outpatient follow-up, including new diagnoses related to abnormal pulmonary function, cardiac arrhythmias, myocardial inflammation, and neurological impairment. Findings were robust to multiple sensitivity analyses and several of these phenotypic associations were detectable in the cohort as early as January 2021.Interpretation: In this regional US registry, survival from COVID-19 was associated with new diagnoses affecting multiple organ systems, which may reflect late effects of inflammation and vascular injury or the sequelae of severe illness among hospitalized survivors. These findings can inform efforts for longitudinal health surveillance of COVID-19 survivors.Funding: This study was supported in part by the American Thoracic Society (VEK), and National Institutes of Health continuing education grant NIH T15 LM007450 (VEK), and research grants NIH K01 HL15775-01 (VEK), NIH U01 HG011166-01S1 (JFP), and NIH R01 GM139891-01 (WQW).Declaration of Interest: The authors declare no competing financial or competing interests.Ethical Approval: This study was conducted with approval from the Vanderbilt University Institutional Review Board (study approval numbers: #200512, #200731) under a waiver of informed consent