Dysregulated immunity in SARS-CoV-2 infected pregnant women

Abstract

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.

Comprehensive analysis of COVID-19 during pregnancy

“…In a recent pre-print, Sherer et al. reported that pregnant individuals with COVID-19 generated the same level of anti-S protein IgG but lower levels of anti-RBD IgG compared to individuals that were not pregnant [ 29 ]. Pregnant individuals with COVID-19 were less likely to have detectable neutralizing antibodies against SARS-CoV-2 than those that were not pregnant, suggesting that the quality of the antibody response against SARS-CoV-2 during pregnancy was inferior.…”

“…Sherer et al. reported that while the level of SARS-CoV-2 S protein IgG was the same in maternal serum compared to umbilical cord blood, the level of neutralizing antibodies was reduced in the umbilical cord blood [ 29 ]. However, both the expression of FcRn in the placenta and the transfer of anti-tetanus IgG in pregnant individuals with and without COVID-19 was the same.…”

“…However, both the expression of FcRn in the placenta and the transfer of anti-tetanus IgG in pregnant individuals with and without COVID-19 was the same. These results suggest that the process of passive immunization from mother to fetus is not broadly hindered by SARS-CoV-2 infection [ 29 ], which is seen with placental malaria and HIV [ 78 , 79 ]. IgG subclass and post-translational modification such as Fc glycosylation have also been suggested to influence the transfer ratio of different antibodies [ [79] , [80] , [81] ].…”

“…However, Sherer et al. reported no difference in maternal serum IL-6 between healthy pregnant individuals and those with mild to moderate COVID-19 in a recent pre-print [ 29 ]. In light of the association between systemic inflammation and pregnancy complications, there is a need for further examination of the impact of SARS-CoV-2 induced cytokines on pathogenesis over the course of pregnancy.…”

Immunity to SARS-CoV-2: Lessons Learned

“…At this stage in the pandemic, there is limited evidence regarding the immune response to COVID-19 during pregnancy, postpartum, breastfeeding, and in neonates. None of the completed or ongoing phase 3 clinical studies of vaccines include pregnant women (108), and further research is needed to understand the immune response in these special populations.…”