Multiorgan Outcomes Following COVID-19 Vaccine vs Infection: 30M Analysis

ABSTRACT Background Cardiovascular and cerebrovascular risks of SARS-CoV-2 infection and mRNA vaccination remain incompletely defined and lacking comparative outcomes such as sex-specific vulnerabilities. Methods Using the TriNetX Research Network (December 2020–December 2024), we identified four mutually exclusive cohorts: uninfected/unvaccinated (naïve), infected/unvaccinated, vaccinated-only, and infected/vaccinated (hybrid immunity). We compared 50 prespecified cardiovascular, cerebrovascular, and mortality outcomes across four pairwise cohort comparisons, with analyses stratified by sex and time of event windows (0–3, 3– 6, 6–9, and >9months). Different vaccine dosing strategies were analyzed. Results Among 30.3 million individuals, infection was associated with a 4.5-fold increased mortality in males and 4.0-fold in females ( p