Compromised SARS-CoV-2 neutralizing antibody response in cord blood versus mothers

Background: Maternal antibodies are important for infant immunity, and understanding the maternal and umbilical cord antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will be important for neonatal management and maternal vaccination strategies. Methods: The dynamics of maternal/ umbilical cord antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were analyzed in 81 samples from 69 pregnant women studied between April 2020 and January 2021. Binding IgG, IgA and IgM antibodies to RBD were measured by enzyme-linked immunosorbent assay (ELISA) in both maternal and cord blood. Neutralization was assessed using codon-optimized full-length G614 Spike-pseudotyped virus (VRC7480.D614G). Results: Among the 69 pregnant women, 57 were either symptomatic or asymptomatic infection and 17 samples were taken during the time of delivery resulting in paired maternal/umbilical cord blood samples. Among the maternal samples tested, the RBD specific IgG were detected in 93%, IgA were detected in 67% and IgM were detected in 79%. The RBD-specific IgG was detected in 12 of 17 (70%) umbilical cord blood, but IgM and IgA were not detected in the cord blood samples. The IgG antibody concentration were significantly (P < 0.004) lower (7 fold) in the cord blood when compared to maternal blood. However, the cord blood IgG titers were positively correlated with maternal IgG titers (r = 0.59;P < 0.003). In line with that, the circulating T-follicular helper cells (p<0.0001) and signaling lymphocytic activation molecule family 1(SLAMF1) were lower (p<0.004) in cord relative to maternal blood. Among the samples tested, 71.4% had neutralization titers. Interestingly, the neutralization capacity of plasma from cord blood was negative when compared to maternal blood (mean titer of 20 vs 2128 respectively), suggesting that cord blood does not have capacity to neutralize the SARS-CoV-2 virus. Conclusion: In this cohort study, maternal IgG, IgA and IgM antibodies to RBD of SARS-CoV-2 were seen in maternal samples. However the cord blood IgG levels were significantly lower and did not show positive titers for IgA and IgM. Although both maternal and cord blood has RBD binding antibodies, there is no neutralization seen in any of the cord blood tested compared to respective maternal blood. Our findings demonstrate that maternally-derived SARS-CoV-2 specific antibodies lack neutralization potential to provide neonatal protection from COVID-19. (Figure Presented).