Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection

Abstract

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.

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

“…Indeed, neonates with raised IP-10 concentrations were born to mothers who had high plasma IP-10 measurements, although in general concentrations were significantly lower in neonates compared to mothers. However, in the case of cord plasma CXCL8, a chemokine that correlated strongly with maternal IL-1β (previously associated with maternal SARS-CoV-2 infection 35 ), levels were significantly higher than those observed in their mothers, suggesting that at least some of these elevated cytokines were neonatally derived, and a direct response to maternal infection. Elevated cord plasma cytokines, including CXCL8, have been previously observed in some neonates born to SARS-CoV-2-positive mothers 17 .…”

Maternal cytokine response after SARS-CoV-2 infection during pregnancy

“…The sensitivity analysis excluding participants in active labor showed similar results for cluster Eigenvalues compared between cases and controls (Supplementary table IX). CoV-2 infected pregnant people (n=33) and non-infected pregnant people (n=17) based on RT-PCR testing and did not find altered gene expression levels of IL-1β and IL-6 [18]. However, they did find increased levels of IL-1β in maternal blood taken within 14 days of infection compared to samples taken 14 days after infection [18].…”

“…CoV-2 infected pregnant people (n=33) and non-infected pregnant people (n=17) based on RT-PCR testing and did not find altered gene expression levels of IL-1β and IL-6 [18]. However, they did find increased levels of IL-1β in maternal blood taken within 14 days of infection compared to samples taken 14 days after infection [18]. RT-PCR testing is commonly used to detect viral RNA of SARS-CoV-2 in respiratory secretions and a positive test is often considered an indicator of active viremia, although this is not guaranteed [39].…”

“…Another retrospective study showed that plasma cytokine levels of IL-2, IL-5, IL-10 and IL-12 were similar in pregnant and non-pregnant SARS-CoV-2 infected people, and were decreased compared to healthy pregnant people (N=25) [17]. Sherer et al found that gene expression of IL-1β and IL-6 in whole blood samples of pregnant people at delivery was not altered within 14 days after a positive SARS-CoV-2 test compared to pregnant people with a negative test (N=33) [18]. Although previous studies suggest peripheral blood cytokine changes in response to acute SARS-CoV-2 infection during pregnancy, they do not fully align with each other, which may be due to limited sample size, varying study design or other factors influencing cytokine levels including nutrition, BMI, and previous infections.…”

Lack of effects on female fertility or pre- and postnatal development of offspring in rats after exposure to AS03-adjuvanted recombinant plant-derived virus-like particle vaccine candidate for COVID-19

“…In the context of COVID-19 pandemic and the elevated risk of serious outcomes in pregnancy [ 42 ], it is crucial for pregnant women to be adequately protected against viral infection. Interestingly, data available suggest that antibodies induced by natural SARS-CoV-2 infection during pregnancy may not confer the same neutralizing potential [ 43 ] and be less efficiently transferred to the fetus compared to those generated by vaccination [ 44 ]. In the current study, we reported placental transfer of SARS-CoV-2-specific IgG to the fetuses at ∼15% of the levels seen in the dams.…”