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

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

doi:10.1136/bmjopen-2021-053036

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

BMJ Open. 2021 Jul 7;11(7):e053036. doi: 10.1136/bmjopen-2021-053036.

Authors

Dongli Song^{1

2}, Mary Prahl³, Stephanie L Gaw⁴, Sudha Rani Narasimhan^{1

2}, Daljeet S Rai⁵, Angela Huang¹, Claudia V Flores¹, Christine Y Lin⁴, Unurzul Jigmeddagva³, Alan Wu⁶, Lakshmi Warrier⁷, Justine Levan⁷, Catherine B T Nguyen⁷, Perri Callaway⁷, Lila Farrington⁷, Gonzalo R Acevedo⁷, Veronica J Gonzalez⁴, Anna Vaaben⁷, Phuong Nguyen⁸, Elda Atmosfera⁸, Constance Marleau⁸, Christina Anderson^{1

2}, Sonya Misra^{1

2}, Monica Stemmle^{2

9}, Maria Cortes¹, Jennifer McAuley¹, Nicole Metz¹, Rupalee Patel¹, Matthew Nudelman¹⁰, Susan Abraham^{2

9}, James Byrne^{11

12}, Priya Jegatheesan^{13

2}

Affiliations

¹ Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA.
² Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
³ Department of Pediatrics, Division of Pediatric Infectious Diseases and Global Health, University of California San Francisco, San Francisco, California, USA.
⁴ Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA.
⁵ Department of Family Medicine, Stanford University School of Medicine, Stanford, California, USA.
⁶ Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
⁷ Department of Medicine, University of California San Francisco, San Francisco, California, USA.
⁸ Department of Pathology, Santa Clara Valley Medical Center, San Jose, California, USA.
⁹ Department of Pediatrics, Division of Pediatric Hospital Medicine, Santa Clara Valley Medical Center, San Jose, California, USA.
¹⁰ Department of Pediatrics, Marshall University, Huntington, West Virginia, USA.
¹¹ Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Santa Clara Valley Medical Center, San Jose, California, USA.
¹² Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California, USA.
¹³ Department of Pediatrics, Division of Neonatology, Santa Clara Valley Medical Center, San Jose, California, USA Priya.Jegatheesan@hhs.sccgov.org.

Abstract

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.

Keywords: COVID-19; immunology; neonatology; paediatric infectious disease & immunisation.

Abstract

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