Objective: A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS). Using electronic health records data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models.
Methods: In our cohort of 63,675 COVID-19 positive patients, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance.
Results: In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the COVID-19 positive cohort with an at least 2.9-fold increased risk for PASC.
Conclusions: The uncovered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with a potential for risk stratification approaches.
Keywords: COVID-19; Coronavirus Disease-2019; PASC; Post-Acute Sequelae of SARS CoV-2 infection; electronic health records; long COVID; phenome-wide association study; phenotype risk score; post-COVID conditions.