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

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 25, 2021, 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 and had received at least one SARS-CoV-2 PCR test. 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 74,032 pairs and the mRNA-1273 group included 55,098 pairs. In BNT162b2 and mRNA-1273 groups, median age was 72 (interquartile range [IQR]: 64-75) and 72 (IQR: 66-77) years, 69,426 (93.8%) and 52,241 (94.8%) were male, and 43,039 (58.1%) and 37,218 (67.5%) were non-Hispanic White, respectively. Effectiveness of a third dose of BNT162b2 or mRNA-1273 compared to the primary series was 45.7% (95% confidence interval [CI]: 37.9-52.5%) and 46.6% (95% CI: 36.4-55.3%) for documented SARS-CoV-2 infection and 44.8% (95% CI: 26.6-58.4%) and 50.0% (95% CI: 26.2-66.1%) 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. Funding None.