Scanning the medical phenome to identify new diagnoses after recovery from COVID-19 in a US cohort

OBJECTIVE: COVID-19 survivors are at risk for long-term health effects, but assessing the sequelae of COVID-19 at large scales is challenging. High-throughput methods to efficiently identify new medical problems arising after acute medical events using the electronic health record (EHR) could improve surveillance for long-term consequences of acute medical problems like COVID-19. MATERIALS AND METHODS: We augmented an existing high-throughput phenotyping method (PheWAS) to identify new diagnoses occurring after an acute temporal event in the EHR. We then used the temporal-informed phenotypes to assess development of new medical problems among COVID-19 survivors enrolled in an EHR cohort of adults tested for COVID-19 at Vanderbilt University Medical Center. RESULTS: The study cohort included 186 105 adults tested for COVID-19 from March 5, 2020 to November 1, 2021; of which 30 088 (16.2%) tested positive. Median follow-up after testing was 412 days (IQR 274–528). Our temporal-informed phenotyping was able to distinguish phenotype chapters based on chronicity of their constituent diagnoses. PheWAS with temporal-informed phenotypes identified increased risk for 43 diagnoses among COVID-19 survivors during outpatient follow-up, including multiple new respiratory, cardiovascular, neurological, and pregnancy-related conditions. Findings were robust to sensitivity analyses, and several phenotypic associations were supported by changes in outpatient vital signs or laboratory tests from the pretesting to postrecovery period. CONCLUSION: Temporal-informed PheWAS identified new diagnoses affecting multiple organ systems among COVID-19 survivors. These findings can inform future efforts to enable longitudinal health surveillance for survivors of COVID-19 and other acute medical conditions using the EHR.