Objectives: To evaluate the effectiveness of COVID-19 vaccinations (initial and booster) during pre-Delta, Delta, and Omicron dominant periods among pregnant people via (1) COVID-19 incident and severe infections among pregnant people who were vaccinated vs. unvaccinated and (2) post-COVID-19 vaccination breakthrough infections and severe infections among vaccinated females who were pregnant vs. non-pregnant.
Design: Retrospective cohort study using nationally sampled electronic health records data from the National COVID Cohort Collaborative (N3C), December 10, 2020, to June 07, 2022.
Participants: Cohort 1 included pregnant people (15-55 years), and Cohort 2 included vaccinated females of reproductive age (15-55 years).
Exposures: (1) COVID-19 vaccination and (2) pregnancy.
Main outcome measures: Adjusted hazard ratios (aHRs) for COVID-19 incident or breakthrough infections and severe infections (i.e., COVID-19 infections with related hospitalizations).
Results: In Cohort 1, 301,107 pregnant people were included. Compared to unvaccinated pregnant people, the aHRs for pregnant people with initial vaccinations during pregnancy of incident COVID-19 were 0.77 (95% CI: 0.62, 0.96) and 0.88 (95%CI: 0.73, 1.07) and aHRs of severe COVID-19 infections were 0.65 (95% CI: 0.47, 0.90) and 0.79 (95% CI: 0.51, 1.21) during the Delta and Omicron periods, respectively. Compared to pregnant people with full initial vaccinations, the aHR of incident COVID-19 for pregnant people with booster vaccinations was 0.64 (95% CI: 0.58, 0.71) during the Omicron period. In Cohort 2, 934,337 vaccinated people were included. Compared to vaccinated non-pregnant females, the aHRs of severe COVID-19 infections for people with initial vaccinations during pregnancy was 2.71 (95% CI: 1.31, 5.60) during the Omicron periods.
Conclusions: Pregnant people with initial and booster vaccinations during pregnancy had a lower risk of incident and severe COVID-19 infections compared to unvaccinated pregnant people across the pandemic stages. However, vaccinated pregnant people still had a higher risk of severe infections compared to non-pregnant females.
Keywords: COVID-19 pandemic; pregnant people; vaccine effectiveness.