Single cell RNA sequencing reveals immunological rewiring at the maternal fetal interface following asymptomatic/mild SARS-CoV-2 infection

Pregnant women are at increased risk for severe COVID-19, though the majority experience asymptomatic/mild disease. While severe COVID-19 is associated with immune activation at the maternal-fetal interface, the immune responses to asymptomatic/mild COVID-19 during pregnancy in blood and placenta remain unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic/mild disease and 15 SARS-naive pregnant women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling pathways while those associated with cytokines and chemokines signaling were upregulated in blood monocyte-derived decidual macrophages. Furthermore, SARS-CoV-2 infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of regulatory T cells. Interestingly, frequencies of both cytotoxic CD4 and CD8 T cells increased in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. Collectively, these observations indicate that even asymptomatic/mild COVID-19 during pregnancy results in significant remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.