Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study

Song, Dongli; Prahl, Mary; Gaw, Stephanie L.; Narasimhan, SudhaRani; Rai, Daljeet; Huang, Angela; Flores, Claudia; Lin, Christine Y.; Jigmeddagva, Unurzul; Wu, Alan H.B.; Warrier, Lakshmi; Levan, Justine; Nguyen, Catherine B.T.; Callaway, Perri; Farrington, Lila; Acevedo, Gonzalo R.; Gonzalez, Veronica J.; Vaaben, Anna; Nguyen, Phuong; Atmosfera, Elda; Marleau, Constance; Anderson, Christina; Misra, Sonya; Stemmle, Monica; Cortes, Maria; McAuley, Jennifer; Metz, Nicole; Patel, Rupalee; Nudelman, Matthew; Abraham, Susan; Byrne, James; Jegatheesan, Priya

OBJECTIVE: To investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants. DESIGN: A prospective observational study. SETTING: A public healthcare system in Santa Clara County (CA, USA). PARTICIPANTS: Women with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.