The COVID-19 pandemic, beginning in March 2020, exposed the population to heterogeneous exposures to SARS-CoV-2 antigens due to repeated infection waves and the rollout of mRNA and adenovirus-vectored vaccines. While pregnancy doesn't increase the risk of SARS-CoV-2 infection, infection during pregnancy does increase the risk of morbidity and mortality. Vaccination during pregnancy, however, has not shown increased risks or adverse outcomes. Studies have shown that vaccination during pregnancy leads to a robust IgG antibody response in mothers and passive transfer of antibodies to their neonates, reducing maternal infections and preventing COVID-19 hospitalization in infants up to six months old. Booster doses are recommended and increase antibody levels and neutralizing antibodies against emerging variants. However, the benefits to neonates born to mothers with full vaccination and boosting after prior infection remain unclear. The study aims to investigate the impact of vaccination and infection history on antibody levels in pregnant individuals and the passive transfer of these antibodies to their neonates, focusing on the effectiveness against various SARS-CoV-2 variants, including Omicron.

Prior research demonstrates that vaccination during pregnancy elicits robust immunoglobulin G (IgG) antibody responses in mothers and facilitates passive antibody transfer to their neonates. This passive transfer has been shown to reduce maternal SARS-CoV-2 infections and prevent COVID-19 hospitalization in infants. Booster doses following primary vaccination have been shown to increase antibody levels and enhance neutralization of emerging SARS-CoV-2 variants. However, the combined effects of vaccination, boosting, and prior infection on both maternal and neonatal antibody responses, particularly against newer variants, have not been extensively studied. Existing studies have often focused on single aspects (vaccination or infection) rather than the interplay of these factors.

This study enrolled 4600 pregnant patients who delivered between April 18, 2020, and April 27, 2022, at an academic medical center in New York City. Patients were categorized based on their vaccination history (no vaccination (NoVx), partially vaccinated (PartVx), fully vaccinated (FullVx), boosted (BoostVx)) and SARS-CoV-2 infection history (Inf). Maternal peripheral blood and umbilical cord blood samples were collected at delivery. IgG antibodies against SARS-CoV-2 spike protein were measured using a fluorescence-based reporting system. A subset of 259 patients with documented infection dates underwent neutralization assays against the ancestral (B.1), BA.1, and BA.5 Omicron variants using pseudotyped viruses. Neutralization activity was determined by measuring the half-maximal neutralization titers (NT50). Statistical analyses included Wilcoxon rank-sum tests, linear regression, mixed ANOVA, and Spearman correlation analyses.

The study found that each additional vaccine dose significantly increased maternal IgG levels. Prior SARS-CoV-2 infection further enhanced IgG levels across all vaccination cohorts. The highest IgG levels were observed in patients with both a history of infection and a booster dose. These patients also demonstrated the highest neutralizing activity against B.1, BA.1, and BA.5 variants. Maternal IgG levels strongly correlated with neonatal umbilical cord blood IgG levels (r=0.93, p<2.2e-16). Neonates born to boosted mothers with prior infection exhibited the highest neutralizing activity against all three variants tested. The correlation between maternal and neonatal neutralizing antibody levels was also high for all variants. There was no significant difference in neutralizing activity between Moderna and Pfizer-BioNTech vaccines in either mothers or neonates.

This large-scale study demonstrates the significant impact of vaccination, boosting, and prior infection on both maternal and neonatal antibody responses to SARS-CoV-2. The findings underscore the importance of vaccination and booster doses, particularly for individuals with a history of infection, in achieving optimal antibody levels and neutralizing activity against various variants. The strong correlation between maternal and neonatal antibody levels confirms effective transplacental antibody transfer, providing passive immunity to newborns. These results support current recommendations for COVID-19 vaccination and boosting during pregnancy, highlighting the benefits for both the mother and the neonate.

This study provides robust evidence that SARS-CoV-2 vaccination and boosting, especially in the context of prior infection, significantly enhances both maternal and neonatal antibody responses, offering substantial protection against various SARS-CoV-2 variants. The high correlation of maternal and neonatal antibody levels strongly supports the continued recommendation for COVID-19 vaccination and boosting during pregnancy. Future research could explore the long-term duration of this passive immunity in neonates and the effectiveness against future emerging variants.

Limitations include reliance on self-reported infection history, imprecise infection dates for some patients, and the inability to precisely determine the infecting variant in all cases. The study also lacked detailed analysis of gestational age at each vaccination and did not include patients who received bivalent booster doses. Some patients without documented infection might have had mild or asymptomatic infections, potentially leading to misclassification.