Maternal Antibody Response, Neutralizing Potency, and Placental Antibody Transfer After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Abstract

Objective: To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer.

Methods: We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti-receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency.

Results: Thirty-two paired samples were analyzed. Detectable anti-receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti-receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5-2.4] vs log 2.7 [2.9-1.4], P=.03). Median (interquartile range) maternal anti-receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5-2.4] vs log 2.67 [2.8-1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67-0.88).

Conclusions: These results demonstrate robust maternal neutralizing and anti-receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study.

Fig. 1.. Percentage of maternal and cord blood samples with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) immunoglobulin (Ig)G, IgM, and IgA antibody titers, neutralizing antibodies, and nucleocapsid antigen.

Joseph. Maternal Immune Response to COVID-19. Obstet Gynecol 2021.

Fig. 2.. Symptomatic maternal infection significantly alters the endpoint titers (EDT) of maternal (A) and cord blood, (B) anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) immunoglobulin (Ig)G antibodies, as well as maternal (C) IgA antibodies, but does not alter the EDT of SARS-CoV-2 IgA (D) cord blood or IgM (E and F) and neutralizing antibodies (G and H). Differences in median EDT in maternal blood sera were analyzed using Mann-Whitney U two-tailed test for significance, with P-value set at ≤.05. There was a statistically significant difference in median anti-RBD IgG titers between symptomatic and asymptomatic patients in maternal plasma (log 3.2 [3.5, 2.4] vs log 2.7 [2.9, 1.4], P=.03]) and in median anti-RBD IgA titers (log 2.09 [2.2, 0.6] vs 1.3 [1.9, 0], P=.04]). However, no difference was seen in median maternal neutralizing antibody concentrations (IC50 2.9 [3.2, 1.1] vs 2.7 [3.0, 0], P=.24) or median IgM titers (log EDT 2.2 [2.7, 1.8] vs 2.3 [2.8, 1.9], P=.24) in symptomatic vs asymptomatic women. Cord RBD IgG concentrations were also significantly different according to the presence or absence of symptoms at time of infection (log EDT 2.4 [2.9, 1.8] vs 1.8 [2.2, 0.6], P=.02).

Joseph. Maternal Immune Response to COVID-19. Obstet Gynecol 2021.

Fig. 3.. The latency of maternal infection significantly alters the maternal endpoint titers (EDT) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G antibodies but not cord blood IgG antibodies (A and B) or IgA (C and D), IgM (E and F), or neutralizing (F and H) maternal and cord blood antibodies. Differences in median endpoint titers in maternal blood sera were analyzed using Mann-Whitney U two-tailed test for significance, with P-value set at ≤.05. Median maternal anti–receptor-binding domain (anti-RBD) IgG titers were significantly higher in patients who delivered more than 14 days after a positive polymerase chain reaction test result vs those who delivered within 14 days (log 3.3 [3.5, 2.4] vs log 2.67 [2.8, 1.6], P=.05). Although anti-RBD cord IgG was also higher in those delivering more than 14 days after diagnosis, this was not statistically significant (log 2.4 [2.9, 1.7] vs log 1.8 [2.2, 0.9], P=.07). No between-group difference was seen in those delivering 14 days or less vs more than 14 days in maternal IgA (log 1.3 [1.8, 0] vs log 2.1 [2.1, 0], P=.06), maternal IgM (log 2.3 [2.7, 2.1] vs log 2.3 [2.9, 1.8], P=.78), and neutralizing response (log 2.7 [3.2, 0] vs log 2.8 [3.2, 0], P=.80). COVID-19, coronavirus disease 2019.

Joseph. Maternal Immune Response to COVID-19. Obstet Gynecol 2021.

Fig. 4.. Neonatal/maternal anti–receptor-binding domain (anti-RBD) immunoglobulin (Ig)G ratios in symptomatic vs asymptomatic paired patient samples and in paired patient samples with less than 14 days and more than 14 days after infection (positive polymerase chain reaction test result) to delivery. The fetal/maternal ratio (FMR) was calculated as the ratio between cord blood and maternal RBD IgG endpoint titers. The difference in FMR between groups was not statistically significant.

Joseph. Maternal Immune Response to COVID-19. Obstet Gynecol 2021.