Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

  1. Sebastian Otero
  2. Emily S. Miller
  3. Ashwin Sunderraj
  4. Elisheva D. Shanes
  5. Allison Sakowicz
  6. Jeffery A. Goldstein
  7. Leena B. Mithal

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Abstract

Background

Pregnant persons are at increased risk of severe COVID-19 and adverse obstetric outcomes. Understanding maternal antibody response and transplacental transfer after SARS-CoV-2 infection and COVID-19 vaccination is important to inform public health recommendations.

Methods

This prospective observational cohort study included 351 birthing individuals who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. IgG and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across 1) disease severity for those with SARS-CoV-2 infection and 2) infection versus vaccination.

Findings

There were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection category had higher maternal and cord blood IgG levels (p=0.0001, p=0.0001). Median IgG transfer ratio was 0.87-1.2. Maternal and cord blood IgG were higher after vaccination than infection (p=0.001, p=0.001). Transfer ratio was higher after 90 days in the vaccinated group (p<0.001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (p<0.0001). There were no significant differences by fetal sex.

Interpretation

COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared to SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Reviewer 2

    Review 2: "Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy"

    Reviewers found the research meaningful for maternal antibody response and transplacental transfer among different SARS variants. However, authors could improve the research structure and evidence relating to patient samples, as it could play a key role in human diseases.

  2. Rapid Reviews Infectious Diseases

    Naima Joseph

    Review 1: "Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy"

    Reviewers found the research meaningful for maternal antibody response and transplacental transfer among different SARS variants. However, authors could improve the research structure and evidence relating to patient samples, as it could play a key role in human diseases.

  4. ScreenIT

    SciScore for 10.1101/2022.03.17.22272574: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Institutional Review Board of Northwestern University (reference number STU00212232) with a waiver of informed consent was obtained prior to initiation of this research.
    Consent: This study was approved by the Institutional Review Board of Northwestern University (reference number STU00212232) with a waiver of informed consent was obtained prior to initiation of this research.
    Sex as a biological variableStudy design and patient cohort: This is a prospective observational cohort study of pregnant people who delivered at Northwestern Medicine Prentice Women’s Hospital in Chicago, IL, USA (April 2020-July 2021).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 IgM and IgG were measured in maternal and infant plasma using the Access SARS-CoV-2 IgG and IgM Antibody tests (DXI Platform, Beckman Coulter, Brea CA) in the Northwestern Memorial Hospital CAP/CLIA certified clinical laboratory.
    IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted using STATA/IC version 16.0 (
    STATA/IC
    suggested: None
    Statacorp), R software, and Python 3.10.1.
    Statacorp
    suggested: None
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations include the single timepoint of antibody measurements at delivery per patient and the single center study. Circulating anti-S1 RBD antibody is also only one measure of immune protection and does not account for aspects of immunologic memory. Although we did not specifically measure neutralizing antibody, anti-S IgG correlates closely with neutralizing activity patterns16,38. In addition, given the timeframe of the cohort, the effects of 3rd dose booster vaccination during pregnancy are not assessed. In conclusion, COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG and higher infant IgG levels than natural SARS-CoV-2 infection. Vaccination results in higher transplacental antibody transfer ratios than infection after longer latency. Severity of infection is associated with higher and longer lasting antibodies. Maternal IgG antibody levels decrease over time in pregnant patients following both vaccination and natural infection, reinforcing the importance of vaccination even after infection and booster doses if 5 months have elapsed from initial series, to optimize protection of pregnant individuals and their infants.

    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.

  5. Version published to 10.1101/2022.03.17.22272574v1 on medRxiv