Understanding Post-Acute Sequelae of SARS-CoV-2 Infection through Data-Driven Analysis with Longitudinal Electronic Health Records: Findings from the RECOVER Initiative
The study, conducted using electronic health records (EHR) from two large patient-centered clinical research networks, INSIGHT and OneFlorida+, aimed to characterize the post-acute sequelae of SARS-CoV-2 infection (PASC) in diverse populations. It included data from 11 million patients in New York City and 16.8 million in Florida. By using a high-throughput causal inference pipeline and high-dimensional inverse propensity score adjustment, the study identified a broad range of diagnoses and medications with a significantly higher incidence 30-180 days after confirmed SARS-CoV-2 infection compared to non-infected patients. The results indicated more PASC diagnoses and higher risks in New York City than in Florida, highlighting PASC’s heterogeneity across populations.
Key findings include increased risks of various conditions post-COVID infection, such as:
- Neurological conditions: Encephalopathy, dementia, cognitive problems, sleep disorders, and headache, with a notable increase in the use of the insomnia drug melatonin.
- Skin symptoms: Higher risks of hair loss and pressure ulcers, along with associated medications like witch hazel, collagenase, and bacitracin.
- Respiratory system issues: Significant post-acute manifestations like pulmonary fibrosis, dyspnea, and acute pharyngitis, with an increased use of related medications.
- Circulatory and blood conditions: Increased risks of pulmonary embolism, thromboembolism, chest pain, abnormal heartbeat, anemia, and higher use of anticoagulants and beta-blockers.
- Endocrine, nutritional, and metabolic disorders: Elevated risks of malnutrition, diabetes mellitus, fluid and electrolyte disorders, and edema, coupled with higher use of related medications.
- Digestive system conditions: Increased risks of constipation and abdominal pain with associated medications.
- General and musculoskeletal symptoms: Higher risks of malaise and fatigue, fever, and joint pain, with an increase in the use of pain medications like ibuprofen and acetaminophen.
The study also emphasized the varying burden of these conditions based on factors such as acute phase severity, age, gender, race, and baseline pre-existing conditions. It highlighted the higher risks and incidences of PASC in patients with specific comorbidities, such as coronary artery disease, chronic kidney disease, and chronic pulmonary disease.
In comparing the INSIGHT and OneFlorida+ cohorts, the study found notable heterogeneity in PASC conditions, with the INSIGHT cohort generally exhibiting higher adjusted hazard ratios. Differences in patient characteristics, infection periods, therapeutic approaches, and vaccination rates were considered influential factors in this variability.
Overall, this extensive analysis demonstrates that PASC is a multi-organ disease with a broad spectrum of clinical manifestations, varying significantly across different patient groups and geographical locations.