How age and underlying conditions affect incidence of hospitalization and death after documented COVID-19 diagnosis among individuals aged >=20 years, a retrospective cohort study using PCORnet, April 2022 to March 2025

Abstract Background: COVID-19 vaccinations, therapeutics, and immunity from infection have reduced COVID-19 severity. It is unknown to what extent previously identified risk factors, age and underlying medical conditions (UC), remain associated with severe COVID-19 incidence. Methods: Using electronic health record (EHR) data from PCORnet, we identified individuals aged [≥]20 years with COVID-19 during April 2022-March 2025. We used Poisson regression with cluster-robust sandwich standard errors to estimate adjusted cumulative incidence (aCI) and aCI ratios (aCIR) for hospitalization within 16 days and mortality within 30 days of COVID-19 diagnosis to estimate the association of UCs and UC categories, comparing those with an UC to those without (adjusted for sociodemographic and health characteristics). We examined aCI and aCIR for cancer, cardiac, hepatic, immunosuppression, metabolic, neurologic, pulmonary, renal, psychiatric, and other conditions by age groups: 20-49, 50-64, 65-79, and 80+ years. Results: Among 1,662,679 patients with COVID-19, the cumulative incidence of hospitalization (4.7%, 6.3%, 10.8%, 22.6%) and mortality (0.11%, 0.42%, 1.0%, 3.6%) increased across the 20-49, 50-64, 65-79, and 80+ year old age groups, respectively. Within each age group, aCI for hospitalization and mortality increased with number of UCs, with the highest aCI among those with 3 or more UCs. aCIR by age group demonstrated that UCs, especially 2 or more, were associated with incidence of both outcomes in all age groups. Conclusion: Since 2022, older age has remained strongly associated with hospitalization and mortality after COVID-19 diagnosis. Adults with two or more UCs generally had higher incidence of both outcomes across age groups.