COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection

Objectives To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. Design Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). Results 98 patients completed primary vaccination pre-pregnancy (29·6%) and antenatally (63·3%), 24·2% of whom had antenatal COVID-19, while 7·1% were unvaccinated (28·6% had antenatal COVID-19). None had severe COVID-19. Pre-pregnancy vaccination resulted in vaccination-to-infection delay of 23·3 weeks, which extended to 45·2 weeks with a booster, compared to 16·9 weeks following antenatal vaccination (p<0·001). Infections occurred at 26·2 weeks gestation in women vaccinated pre-pregnancy compared to 36·2 weeks gestation in those vaccinated during pregnancy (p<0·007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio 14·6, p=0·05) and after pre-pregnancy vaccination without a booster (hazard ratio 10·4, p=0·002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. Conclusion Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.