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

  1. Dongli Song
  2. Mary Prahl
  3. Stephanie L Gaw
  4. Sudha Rani Narasimhan
  5. Daljeet S Rai
  6. Angela Huang
  7. Claudia V Flores
  8. Christine Y Lin
  9. Unurzul Jigmeddagva
  10. Alan Wu
  11. Lakshmi Warrier
  12. Justine Levan
  13. Catherine B T Nguyen
  14. Perri Callaway
  15. Lila Farrington
  16. Gonzalo R Acevedo
  17. Veronica J Gonzalez
  18. Anna Vaaben
  19. Phuong Nguyen
  20. Elda Atmosfera
  21. Constance Marleau
  22. Christina Anderson
  23. Sonya Misra
  24. Monica Stemmle
  25. Maria Cortes
  26. Jennifer McAuley
  27. Nicole Metz
  28. Rupalee Patel
  29. Matthew Nudelman
  30. Susan Abraham
  31. James Byrne
  32. Priya Jegatheesan

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Abstract

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.

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  1. Version published to 10.1136/bmjopen-2021-053036
  2. ScreenIT

    SciScore for 10.1101/2021.05.01.21255871: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The study was approved by the institutional review boards of Santa Clara Valley Medical Center.
    Sex as a biological variableStudy design, participants, and procedures: This is a prospective observational study of pregnant mothers with SARS-CoV-2 infection during pregnancy and their infants.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Levels of SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) to the spike protein receptor binding domain (RBD) and nucleocapsid protein (NP) of SARS-CoV-2 were measured using the Pylon 3D automated immunoassay system (ET Healthcare, Palo Alto, CA) as previously described.
    ET Healthcare
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. It was conducted in a single healthcare system. The timing of infection was based on the first positive PCR, which might not represent the precise timing of infection in asymptomatic mothers. Our cohort had few severe cases and premature births before 35 weeks of gestation. Universal screening at the time of admission also introduces a bias in the identification of asymptomatic SARS-CoV-2 cases at or near-term gestation, as the universal screening was not implemented in our prenatal care visits and asymptomatic screening was not readily available in our general community during the study period.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.05.01.21255871v1 on medRxiv