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

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses’ vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy by two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1 variant in the winter of 2022). Time-dependent Cox proportional-hazards regressions models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,689 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83–96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26–99%), and 48% (95% CI 37–57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.