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The decidual compartments of the placenta harbor maternal immune cells (macrophages, natural killer cells, and T cells ), which exhibit mixed signatures of activation and regulatory phenotype that correlate with gestation ( van der Zwan et al., 2018) and can respond to foreign particles at the maternal-fetal interface ( Ander et al., 2019). The immunological landscape of the maternal-fetal interface (placenta) undergoes significant changes during pregnancy. These findings support the hypothesis that pregnancy limits the induction of exuberant peripheral inflammatory responses to SARS-CoV-2 infection that are widely reported in non-pregnant individuals. Furthermore, the cytokine storm that is characteristic of severe COVID-19 in the general population is hardly reported in cases of severe COVID-19 among pregnant patients ( Hojyo et al., 2020 Wang et al., 2020). A recent analysis of the peripheral immune system of mothers with asymptomatic disease revealed an increase in low-density neutrophils (LDNs) but no gross changes in leukocyte frequencies, activation, or function ( De Biasi et al., 2021). These differences are primarily driven by peripheral immune adaptations during pregnancy ( Aghaeepour et al., 2017, 2018) that balance fetal tolerance and growth with host defense. Both vulnerability and immune responses to viral infections during pregnancy can be distinct compared with non-gravid individuals, as observed in influenza, hepatitis E, varicella, and measles ( Jamieson et al., 2006 Kourtis et al., 2014 Sappenfield et al., 2013). While pregnant women with a severe COVID-19 diagnosis are at 62% higher odds of getting admitted to the intensive care unit (ICU) compared with non-pregnant women of reproductive age ( Subbaraman, 2021 Yap et al., 2020), a majority of those who get exposed to the virus experience asymptomatic or mild COVID-19 ( Edlow et al., 2020b Li et al., 2020 Lokken et al., 2020 Panagiotakopoulos et al., 2020). Indeed, a study on severe COVID-19 infections in pregnant women from 18 countries has reported higher rates of adverse outcomes such as mortality, preeclampsia, and preterm birth ( Villar et al., 2021).
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Overwhelming evidence suggests that pregnant women are a high-risk group for COVID-19 ( Subbaraman, 2021). The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant global threat ( Huang et al., 2020). Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood.
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We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown.