Associations of COVID-19 Vaccination and Symptom Severity with SARS-CoV-2 Infection in the Framingham Heart Study

COVID-19 vaccination has been associated with reduced SARS-CoV-2 infection risk, but evidence from community-based cohorts with pre-pandemic clinical data remains limited. We examined 2547 Framingham Heart Study participants (mean age, 59 years; 59% women) enrolled in the Collaborative Cohort of Cohorts for COVID-19 Research. Multivariable logistic regression evaluated associations of vaccination status, vaccine type, and post-vaccination symptom severity with recorded SARS-CoV-2 infection. Among participants, 265 had recorded infections. Compared with unvaccinated participants, Moderna and Pfizer recipients had lower odds of infection (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.26–0.52; and OR, 0.32; 95% CI, 0.22–0.44, respectively). Any vaccination was associated with lower odds of infection (OR, 0.35; 95% CI, 0.27–0.46). Post-vaccination symptom severity was not associated with infection. In a sensitivity analysis treating vaccination as time-varying, the adjusted hazard ratio was 0.53 (95% CI, 0.26–1.08). These observational associations were sensitive to exposure timing and may be affected by residual confounding and unmeasured calendar-time factors; they should not be interpreted as causal estimates of vaccine effectiveness.