Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study
James Byrne,
Priya Jegatheesan,
Matthew Nudelman,
Dongli Song,
Angela Huang,
Phuong Nguyen,
Maria Cortes,
Alan Wu,
Mary Prahl,
Stephanie L Gaw,
Sudha Rani Narasimhan,
Daljeet S Rai,
Claudia V Flores,
Christine Y Lin,
Unurzul Jigmeddagva,
Lakshmi Warrier,
Justine Levan,
Catherine B T Nguyen,
Perri Callaway,
Lila Farrington,
Gonzalo R Acevedo,
Veronica J Gonzalez,
Anna Vaaben,
Elda Atmosfera,
Constance Marleau,
Christina Anderson,
Sonya Misra,
Monica Stemmle,
Jennifer McAuley,
Nicole Metz,
Rupalee Patel,
Susan Abraham
Affiliations
James Byrne
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Santa Clara Valley Medical Center, San Jose, California, USA
Priya Jegatheesan
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Matthew Nudelman
Department of Pediatrics, Marshall University, Huntington, West Virginia, USA
Dongli Song
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Angela Huang
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Phuong Nguyen
AIP Foundation
Maria Cortes
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Alan Wu
Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA
Mary Prahl
Department of Pediatrics, Division of Pediatric Infectious Diseases and Global Health, University of California San Francisco, San Francisco, California, USA
Stephanie L Gaw
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA
Sudha Rani Narasimhan
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Daljeet S Rai
Department of Family Medicine, Stanford University School of Medicine, Stanford, California, USA
Claudia V Flores
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Christine Y Lin
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA
Unurzul Jigmeddagva
Department of Pediatrics, Division of Pediatric Infectious Diseases and Global Health, University of California San Francisco, San Francisco, California, USA
Lakshmi Warrier
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Justine Levan
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Catherine B T Nguyen
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Perri Callaway
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Lila Farrington
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Gonzalo R Acevedo
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Veronica J Gonzalez
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA
Anna Vaaben
Department of Medicine, University of California San Francisco, San Francisco, California, USA
Elda Atmosfera
Department of Pathology, Santa Clara Valley Medical Center, San Jose, California, USA
Constance Marleau
Department of Pathology, Santa Clara Valley Medical Center, San Jose, California, USA
Christina Anderson
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Sonya Misra
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Monica Stemmle
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
Jennifer McAuley
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Nicole Metz
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Rupalee Patel
Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA
Susan Abraham
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
Objective To investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.Design A prospective observational study.Setting Public healthcare system in Santa Clara County (California, USA).Participants Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 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 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 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 with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1–4, 5–12, and 13–28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection.Conclusions Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.
