Waning of the Humoral Response to SARS-CoV-2 in Pregnancy is Variant-Dependent

ImportanceThe SARS-CoV-2 alpha variant posed increased risk for COVID-19 complications in pregnant women. However, its impact on the maternal humoral response and placental IgG transport remains unclear. ObjectiveTo characterize the maternal humoral waning and neonate immunity acquired during the 3rd COVID-19 wave in Israel, dominated by the Alpha variant, as compared to earlier Wildtype infections and humoral response to vaccination across gestation. DesignMaternal and fetal blood serum were collected at delivery since April 2020 from parturients. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel supplemented with additional HA-coupled microspheres. SettingA nationwide multicenter cohort study on SARS-CoV-2 infections and vaccination during pregnancy. ParticipantsExpectant women presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 primary groups: SARS-CoV-2 positive (n = 157) and fully vaccinated during pregnancy (n = 125), and unvaccinated noninfected controls matched to the infected group by BMI, maternal age, comorbidities and gestational age (n = 212). Eligibility criteria included pregnant women without active COVID-19 disease, age [≥]18 years and willingness to provide informed consent. Main Outcome(s) and Measure(s)Pregnant womens humoral response is dependent on the SARS-CoV-2 strain. ResultsThe humoral response to infection as detected at birth, showed a gradual and significant decline as the interval between infection/vaccination and delivery increased. Significantly faster decay of antibody titers was found for infections occurring during the 3rd wave compared to earlier infections/vaccination. Cord blood IgG antigens levels correlated with maternal IgG. However, cord IgG-HA variance significantly differed in SARS-CoV2 infections as compared to the other groups. No sexual dimorphism in IgG transfer was observed. Lastly, high fetal IgM response to SARS-CoV-2 was detected in 17 neonates, all showing elevated IgM to N suggesting exposure to SARS-Cov-2 antigens. Conclusions and RelevanceInfections occurring during the 3rd wave induced a faster decline in humoral response when compared to Wildtype infections or mRNA BNT162b2 vaccination during pregnancy, consistent with a shift in disease etiology and severity induced by the Alpha variant. Vaccination policies in previously infected pregnant women should consider the timing of exposure along pregnancy as well as the risk of infection to specific variants of concern. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the difference in the maternal-fetal humoral response between Alpha variant and SARS-CoV-2 Wildtype infections? FindingsIn this nationwide multicenter study including 494 pregnant women, the maternal humoral response to Alpha variant infection was weaker and shorter when compared to Wildtype infections. Placental transport compensated for the maternal waning of immunity. Fetal sex did not affect humoral response. MeaningVaccination policies should be adjusted to account for the timing of infection and the SARS-CoV-2 variant.