Dysregulated immunity in SARS-CoV-2 infected pregnant women

Sherer, M. L.; Lei, J.; Creisher, P.; Jang, M.; Reddy, R.; Voegtline, K.; Olson, S.; Littlefield, K.; Park, H.-S.; Ursin, R. L.; Ganesan, A.; Boyer, T.; Brown, D. M.; Walch, S.; Antar, A. A. R.; Manabe, Y. C.; Jones-Beatty, K.; Golden, W. C.; Satin, A. J.; Sheffield, J. S.; Pekosz, A.; Klein, S.; Burd, I.

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 IL1{beta}, 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.