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[Preprint]. 2020 Nov 16:2020.11.13.20231373. [Version 1] doi: 10.1101/2020.11.13.20231373

Dysregulated immunity in SARS-CoV-2 infected pregnant women

Morgan L Sherer, Jun Lei, Patrick Creisher, Minyoung Jang, Ramya Reddy, Kristin Voegtline, Sarah Olson, Kirsten Littlefield, Han-Sol Park, Rebecca L Ursin, Abhinaya Ganesan, Theresa Boyer, Diane M Brown, Samantha N Walch, Annukka A R Antar, Yukari C Manabe, Kimberly Jones-Beatty, William Christopher Golden, Andrew J Satin, Jeanne S Sheffield, Andrew Pekosz, Sabra L Klein, Irina Burd
PMCID: PMC7685337  PMID: 33236024

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.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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