Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human clinical isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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Pregnancy and COVID-19According to United States (U.S.). Center for Disease Control (CDC), ¼ of reproductive aged women (i.e., 15-49 years of age) hospitalized with COVID-19 from March 1-August 22, 2020 were pregnant, and pregnant women were more likely to require mechanical ventilation than nonpregnant women (1). The CDC also reports that women infected with SARS-CoV-2 during pregnancy are at a higher risk for preterm birth (2). Gestation-associated physical, immunological, and endocrinological changes typically place pregnant women and their fetuses at greater risk for severe complications caused by infectious diseases, which is not unique to SARS-CoV-2 (3). Vaccination in pregnant womenVaccines are the best defense against many infectious diseases, including COVID-19, with numerous diverse platforms already authorized for use or in Phase III randomized clinical trials (4). The COVID-19 mRNA vaccines (Pfizer-BioNtech BNT162b2 and Moderna mRNA-1273) currently utilized for mass vaccination are not live vaccines, nor do they use an adjuvant. As such, the American College of Obstetricians and Gynecologists (ACOG), and Society for Maternal-Fetal Medicine (SMFM) recommend that COVID-19 vaccines should not be withheld from pregnant and lactating individuals. To date, however, none of the approved COVID-19 vaccines have been tested for safety, immunogenicity, reactogenicity, or efficacy in pregnant women or for effects on fetal programming. The CDC and the independent Advisory Committee on Immunization Practices (ACIP) position on the Pfizer-BioNTech and Moderna COVID-19 vaccines is that

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease-causing pathogen of the COVID-19 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe COVID-19 disease and are at higher risk for preterm birth compared to uninfected pregnant women. Despite this evidence, the immunological effects of SARS-CoV-2 infection during pregnancy remain understudied. 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. Study Design Immune responses to SARS-CoV-2 were analyzed using samples from pregnant (n=33) and non-pregnant (n=17) women who had either tested positive (pregnant n=22; non-pregnant n=17) or negative for SARS-CoV-2 (pregnant n=11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we evaluated 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. 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. 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 SARS-CoV-2 nAb was inhibited by infection during pregnancy. Conclusions 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.

ImportanceThe effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated.ObjectiveTo 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.DesignImmune 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.SettingJohns Hopkins Hospital (JHH)ParticipantsPregnant 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.ExposuresSARS-CoV-2Main Outcomes and MeasuresParticipant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression.ResultsSARS-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 RelevanceSARS-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.