Distinct Cellular Immune Responses to SARS-CoV-2 in Pregnant Women1

Pregnant women are at increased risk of adverse outcomes resulting from SARS-CoV-2 infection, including preeclampsia and preterm birth. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection, and 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. Herein, 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 non-pregnant, 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-β and IL-8 are diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and non-pregnant women, and shed light on the immune mechanisms implicated in COVID-19 during pregnancy.