COVID-19 Vaccine Breakthrough Infections in Veterans Health Administration

Background Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by rising concern of vaccine breakthrough due to SARS-CoV-2 variants, waning protection over time, differential vaccine effectiveness, and regional resurgence of Coronavirus 2019 (COVID-19). Characterizing the frequency and drivers of vaccine breakthrough is necessary to inform COVID-19 control efforts. Methods We performed a retrospective cohort study of vaccine breakthrough infections in fully vaccinated persons in Veterans Health Administration. We applied Cox proportional hazard models to estimate cumulative incidence, assess differences in outcomes by vaccine, and identify associations with individual characteristics as well as time-dependent geographic variation in COVID-19 incidence, proportion of delta variant, and vaccine coverage. Results Among 3,032,561 fully vaccinated persons, documented SARS-CoV-2 infection occurred in 11,197 (0.37%) and COVID-19 hospitalization occurred in 2,080 (0.07%). Compared to Ad26.COV2.S, BNT162b2 and mRNA-1273 had lower occurrence of documented SARS-CoV-2 infection (aHR 0.54, 95% confidence interval (CI) 0.51-0.58; aHR 0.36; 95% CI 0.33-0.38; respectively) and COVID-19 hospitalization (aHR 0.56, 95% CI 0.47-0.66; aHR 0.30; 0.25-0.35; respectively). Documented SARS-CoV-2 infection and COVID-19 hospitalization were associated with younger age, Hispanic or Latino ethnicity, number of comorbidities, and previous SARS-CoV-2 infection. Regional proportion of delta variant and county-level COVID-19 incidence were predictors of vaccine breakthrough events; county-level vaccine coverage was inversely associated. Conclusions Vaccine breakthrough was rare among fully vaccinated persons. mRNA-1273 and BNT162b2 were more protective against documented SARS-CoV-2 infection and COVID-19 hospitalization compared to Ad26.COV2.S. Efforts to limit COVID-19 transmission and bolster vaccine coverage would also curtail vaccine breakthrough.