ABSTRACT
Background: There are limited data on how COVID-19 disease severity and vaccination throughout different trimesters in pregnancy impact maternal neutralizing antibody responses and transplacental transfer to the neonate at birth. Further characterization of the antibody response of in utero SARS-CoV-2 may inform vaccination schedules in pregnancy in order to optimize maternal and neonatal protection. Methods: The COVID-19 Outcomes in Mother-Infant Pairs (COMP) study is a longitudinal cohort of mother-infant dyads diagnosed with PCR-confirmed SARS-CoV-2 at any point during pregnancy. Maternal and cord sera from delivery, as well as infant sera collected at 24 hours of life, were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgA, IgG, and IgM targeting receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Neutralizing antibody (NAb) activity against the original L strain was evaluated in a subset of unvaccinated mother-infant dyads with evidence of IgG transfer or history of severe/critical COVID-19 in pregnancy. Results: Among 115 pregnant women, the NIH COVID-19 severity of illness categories were: 12% asymptomatic, 70% mild/moderate, 11% severe/critical disease, and 7% vaccinated prior to delivery following recovery. Fifty percent of the cohort was diagnosed in the 3rd trimester, and the median diagnosis date to delivery was 61.5 days (IQR 27.75-122.25). The majority (74%) of the cohort produced all three anti-SARS-CoV-2 isotypes, although 5% had no detectable antibody class. Transplacental transfer ratios increased with increasing duration between onset of infection and delivery (Figure 1, r2=0.17). Infant IgG levels (ng/mL) were the highest among neonates born to vaccinated mothers (Figure 1), and maternal IgG levels increased with disease severity, although vaccination elicited a comparable maternal antibody response to severe/critical disease (Figure 1). Among 50 maternal specimens, 80% demonstrated in vitro neutralization activity, and 52% of 33 neonatal specimens had NAb. Conclusion: While transplacental transfer of IgG was high with natural infection and correlates with increasing duration between onset of infection and delivery, only half of analyzed neonatal specimens demonstrated in vitro neutralization activity. Further research is needed to characterize the functionality and kinetics of both maternal and neonatal antibody responses elicited by in utero SARS-CoV-2 natural infection compared with COVID-19 vaccination.