Effectiveness of BNT162b2 mRNA COVID-19 third vaccines during pregnancy: A national observational study in Israel

Abstract BACKGROUND Current guidelines recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. METHODS We conducted a national, population-based, historical cohort study of all pregnant women in Israel who delivered between August 1, 2021 and March 22, 2022. Data were analyzed by COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022) and vaccination status of the women. We compared the third and second doses of vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy. Time-dependent Cox proportional-hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose. Vaccine effectiveness was estimated as 1-HR. RESULTS A total of 82,659 and 33,303 pregnant women were followed during the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents hospitalization with SARS-CoV-2 infection, with estimated effectiveness of 97% (95% CI 95–99%) during the Delta period. During the Omicron period, the third dose, but not the second dose, compared to unvaccinated, significantly effectively protects against COVID-19- related outcomes with estimated effectiveness of 43% (95% CI 31–53%), 97% (95% CI 72–100%), and 94% (95% CI 43–99%) in preventing hospitalization with SARS-CoV-2 infection, significant, and severe disease, respectively. CONCLUSIONS A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, significantly enhanced protection against adverse COVID-19-related outcomes.