Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality.

This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1–7 after the first dose, where no protection by the vaccine is assumed (reference-period).

Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1–115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5–8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%–95%) and 94% (95% CI: 88%–97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%–87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36–1.88), 0.45 (95% CI: .23–.90), and 0.56 (95% CI: .36–.89) in the age groups 16–44, 45–64. and ≥75 years, respectively.

The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.