Antibody response, neutralizing potency, and transplacental antibody transfer following SARS-CoV-2 infection versus mRNA-1273, BNT162b2 COVID-19 vaccination in pregnancy.

OBJECTIVE: To improve our understanding of the immune response, including the neutralization antibody response, following COVID-19 vaccination in pregnancy. METHODS: This was a prospective cohort study comprising patients with PCR-confirmed SARS-CoV-2 infection and patients who received both doses of mRNA COVID-19 vaccine (mRNA-1273, BNT162b2) in pregnancy recruited from two hospitals in Atlanta, GA, USA. Maternal blood and cord blood at delivery were assayed for anti-receptor binding domain (RBD) IgG, IgA and IgM, and neutralizing antibody. The detection of antibodies, titers, and maternal to fetal transfer ratios were compared. RESULTS: Nearly all patients had detectable RBD-binding IgG in maternal and cord samples. The vaccinated versus infected cohort had a significantly greater proportion of cord samples with detectable neutralizing antibody (94% vs. 28%, P < 0.001) and significantly higher transfer ratios for RBD-specific IgG and neutralizing antibodies with a transfer efficiency of 105% (vs. 80%, P < 0.001) and 110% (vs. 90%, P < 0.001), respectively. There was a significant linear decline in maternal and cord blood RBD-specific IgG and neutralizing antibody titers as time from vaccination to delivery increased. CONCLUSIONS: Those who receive the mRNA COVID-19 vaccine mount an immune response that is equivalent to-if not greater than-those naturally infected by SARS-CoV-2 during pregnancy.

Placental Injury and Antibody Transfer after Coronavirus Disease 2019 in Pregnancy.

BACKGROUND: We examined the relationship between placental histopathology and transplacental antibody transfer in pregnant patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Differences in plasma concentrations of anti-receptor biding domain (RBD) immunoglobulin (Ig)G antibodies in maternal and cord blood were analyzed according to presence of placental injury. RESULTS: Median anti-RBD IgG concentrations in cord blood with placental injury (n = 7) did not differ significantly from those without injury (n = 16) (median 2.7 [interquartile range {IQR}, 1.8-3.6] vs 2.7 [IQR, 2.4-2.9], P = 0.59). However, they were associated with lower transfer ratios (median 0.77 [IQR, 0.61-0.97] vs 0.97 [IQR, 0.80-1.01], P = 0.05). CONCLUSIONS: SARS-CoV-2 placental injury may mediate reduced maternal-fetal antibody transfer.

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

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.