Effectiveness of a third dose of BNT162b2 or mRNA-1273 vaccine for preventing post-vaccination COVID-19 infection: an observational study (preprint)

Background BNT162b2 and mRNA-1273 vaccines are highly protective against COVID-19. Concern about waning immunity and reduced effectiveness against SARS-COV-2 variants led to use of a third dose six months after completing the primary series. We used data from the Veterans Health Administration to evaluate the effectiveness of a third dose of BNT162b2 or mRNA-1273 compared to the primary series in preventing post-vaccination COVID-19. Methods During January 1 - November 22, 2020, third dose recipients were matched (1:1) to demographically similar controls who did not receive a third dose. Eligible participants had completed the primary series at least six months (180 days) before recruitment date. Long-term care residents were excluded. Primary outcomes were documented SARS-CoV-2 infection and COVID-19 hospitalization. Effectiveness was estimated as 1-incidence rate ratio. Findings Following matching, the BNT162b2 group included 99,856 pairs and the mRNA-1273 group included 74,116 pairs. In BNT162b2 and mRNA-1273 groups, median age was 72 (interquartile range [IQR]: 65-75) and 72 (IQR: 67-76) years, 94,990 (95.1%) and 71,213 (96.1%) were male, and 61,261 (61.3%) and 52,170 (70.4%) were non-Hispanic White, respectively. Effectiveness of a third dose of BNT162b2 or mRNA-1273 compared to the primary series was 49.4% (95% confidence interval [CI]: 41.2-56.5%) and 46.0% (95% CI: 33.5-56.2%) for documented SARS-CoV-2 infection and 52.3% (95% CI: 33.8-65.6%) and 44.7% (95% CI: 10.7-65.7%) for COVID-19 hospitalization, respectively. Interpretation A third dose of BNT162b2 or mRNA-1273 is moderately effective against post-vaccination COVID-19 infection compared to the primary series.

COVID-19 Vaccine Breakthrough Infections in the Veterans Health Administration. (preprint)

BackgroundVaccination 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. MethodsWe 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. ResultsAmong 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. ConclusionsVaccine 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.