Distinct Cellular Immune Responses to SARS-CoV-2 in Pregnant Women.

Pregnant women are at increased risk of adverse outcomes, including preeclampsia and preterm birth, that may result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection; therefore, recent studies have focused on the humoral response against SARS-CoV-2 in pregnant women. However, the pregnancy-specific cellular immune responses triggered by SARS-CoV-2 infection are poorly understood. In this study, we undertook an extensive in vitro investigation to determine the cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women. First, we show that SARS-CoV-2 particles do not alter the pregnancy-specific oxidative burst of neutrophils and monocytes. Yet, SARS-CoV-2 particles/proteins shift monocyte activation from the classical to intermediate states in pregnant, but not in nonpregnant, women. Furthermore, SARS-CoV-2 proteins, but not particles or peptide pools, mildly enhance T cell activation during pregnancy. As expected, B cell phenotypes are heavily modulated by SARS-CoV-2 particles in all women; yet, pregnancy itself further modified such responses in these adaptive immune cells. Lastly, we report that pregnancy itself governs cytokine responses in the maternal circulation, of which IFN-ß and IL-8 were diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and nonpregnant women and shed light on the immune mechanisms implicated in coronavirus disease 2019 during pregnancy.

Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.