Pregnancy alters IL-1β expression and anti-viral antibody responses during SARS-CoV-2 infection

SHERER, Morgan L.; LEI, Jun; CREISHER, Patrick; JANG, Minyoung; REDDY, Ramya; VOEGTLINE, Kristin; OLSON, Sarah; LITTLEFIELD, Kirsten; PARK, Han-Sol; URSIN, Rebecca L.; GANESAN, Abhinaya; BOYER, Theresa; Elsayed, Nada; BROWN, Diane M.; WALCH, Samantha N.; ANTAR, Annukka A.R.; MANABE, Yukari C.; JONES-BEATTY, Kimberly; CHRISTOPHER GOLDEN, William; SATIN, Andrew J.; SHEFFIELD, Jeanne S.; PEKOSZ, Andrew; KLEIN, Sabra L.; BURD, Irina

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.