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Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

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Key Points

Question  What is the association between maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibody concentrations?

Findings  In this cohort study, SARS-CoV-2 IgG antibodies were transferred across the placenta in 72 of 83 pregnant women who were seropositive, and cord blood IgG concentrations were directly associated with maternal antibody concentrations, whereas IgM antibodies were not detected in any cord blood sera. Transfer ratios were associated with time elapsed from maternal infection to delivery and not associated with severity of maternal infection.

Meaning  Efficient transplacental transfer of SARS-CoV-2 IgG antibodies supports the potential for maternally derived antibodies to provide neonatal protection from SARS-CoV-2 infection.

Abstract

Importance  Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies.

Objective  To assess the association between maternal and neonatal SARS-CoV-2–specific antibody concentrations.

Design, Setting, and Participants  This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads.

Exposures  SARS-CoV-2.

Main Outcomes and Measures  IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data.

Results  The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery.

Conclusions and Relevance  In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

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Article Information

Corresponding Author: Scott E. Hensley, PhD, University of Pennsylvania, 3610 Hamilton Walk, 402A Johnson Pavilion, Philadelphia, PA 19104 (hensley@pennmedicine.upenn.edu); Karen M. Puopolo, MD, PhD, Division of Neonatology, Children’s Hospital of Philadelphia, 800 Spruce St, Philadelphia, PA 19107 (karen.puopolo@pennmedicine.upenn.edu).

Accepted for Publication: January 7, 2021.

Published Online: January 29, 2021. doi:10.1001/jamapediatrics.2021.0038

Author Contributions: Dr Puopolo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Flannery and Gouma contributed equally to this work.

Concept and design: Flannery, Gouma, Dhudasia, Mukhopadhyay, Hensley, Puopolo.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Flannery, Gouma, Dhudasia, Mukhopadhyay, Woodford, Arevalo.

Critical revision of the manuscript for important intellectual content: Gouma, Dhudasia, Mukhopadhyay, Pfeifer, Triebwasser, Gerber, Morris, Weirick, McAllister, Bolton, Anderson, Goodwin, Hensley, Puopolo.

Statistical analysis: Flannery, Gouma, Dhudasia, Mukhopadhyay, Morris.

Obtained funding: Flannery, Hensley, Puopolo.

Administrative, technical, or material support: Flannery, Gouma, Woodford, Triebwasser, Weirick, McAllister, Bolton, Arevalo.

Supervision: Mukhopadhyay, Gerber, Hensley, Puopolo.

Conflict of Interest Disclosures: Dr Hensley reported consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this study. Dr Puopolo reported grants from Children’s Hospital of Philadelphia Foerderer Fund for Excellence and US Centers for Disease Control and Prevention during the conduct of the study. No other disclosures were reported.

Funding/Support: Funding for this study was provided in part by a Children’s Hospital of Philadelphia Foerderer Grant for Excellence to Dr Puopolo.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Jeffrey Lurie (Philadelphia Eagles), Joel Embiid (Philadelphia 76ers), Josh Harris (Philadelphia 76ers), and David Blitzer (Philadelphia 76ers) for philanthropic support that was used to establish the serological assays used in this study. We thank Florian Krammer, PhD (Mt. Sinai; no compensation provided), for providing the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain expression plasmids and Ian Wilson, DPhil (Scripps; no compensation provided), for providing plasmids to express monoclonal CR3022.

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