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

Priya Jegatheesan; Matthew Nudelman; Dongli Song; Angela Huang; 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

doi:10.1136/bmjopen-2021-053036

BMJ Open (Jul 2021)

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

Priya Jegatheesan,
Matthew Nudelman,
Dongli Song,
Angela Huang,
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

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
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

DOI: https://doi.org/10.1136/bmjopen-2021-053036
Journal volume & issue: Vol. 11, no. 7

Abstract

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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.

Published in BMJ Open

ISSN: 2044-6055 (Online)
Publisher: BMJ Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine
Website: https://bmjopen.bmj.com

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