Dysregulated immunity in SARS-CoV-2 infected pregnant women

  1. Morgan L. Sherer
  2. Jun Lei
  3. Patrick Creisher
  4. Minyoung Jang
  5. Ramya Reddy
  6. Kristin Voegtline
  7. Sarah Olson
  8. Kirsten Littlefield
  9. Han-Sol Park
  10. Rebecca L. Ursin
  11. Abhinaya Ganesan
  12. Theresa Boyer
  13. Diane M. Brown
  14. Samantha N. Walch
  15. Annukka A. R. Antar
  16. Yukari C. Manabe
  17. Kimberly Jones-Beatty
  18. William Christopher Golden
  19. Andrew J. Satin
  20. Jeanne S. Sheffield
  21. Andrew Pekosz
  22. Sabra L. Klein
  23. Irina Burd

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Abstract

Importance

The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated.

Objective

To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women.

Design

Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood.

Setting

Johns Hopkins Hospital (JHH)

Participants

Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study.

Exposures

SARS-CoV-2

Main Outcomes and Measures

Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression.

Results

SARS-COV-2 positive pregnant women expressed more IL1β , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy.

Conclusions and Relevance

SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.13.20231373: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of this study include the small sample size as well as significant differences in age, race, and ethnicity between SARS-CoV-2-infected pregnant and non-pregnant women. These differences are attributable to our reliance on convenience sampling and are a result of differences in participant recruitment, in which sample collection from pregnant women was based on time of delivery, and sample collection from non-pregnant women was based on symptom presentation. While there was a significant difference in age between the cohorts, all women in this study were within reproductive ages12. Due to our inability to know precisely when each participant was infected with SARS-CoV-2, we used the number of days between a SARS-CoV-2 PCR test and blood collection as the metric to assess cytokine responses, and additionally used the number of days since symptom onset to evaluate humoral responses over time. These metrics may not accurately represent the time since initial infection, as symptom onset is self-reported and studies have reported PCR positivity for extended periods of time past the initial infection42,43. Our results demonstrate potential differences in the pathogenesis of SARS-CoV-2, including inflammatory and antibody responses to the virus, between pregnant and non-pregnant women. It is well-established that immune responses change dramatically during pregnancy in order to accommodate the developing fetus44. Therefore, understanding the impact of SARS-CoV-2 infection...

    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.

    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.

  2. Version published to 10.1101/2020.11.13.20231373v1 on medRxiv