There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

中文翻译：

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母体 SARS-CoV-2 感染引发性别二态性胎盘免疫反应


人们普遍认为 2019 年冠状病毒病 (COVID-19) 在男性中的患病率较高且严重程度较高。造成这种性别差异的根本机制仍不完全清楚。干扰素反应被认为是成人 COVID-19 疾病的调节剂，并在胎盘抗病毒反应中发挥关键作用。此外，干扰素反应已被证明会改变 Fc 受体表达，因此可能影响胎盘抗体转移。在这里，我们检查了感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的孕妇中母胎抗体转移、病毒诱导的胎盘干扰素反应和胎儿性别的交叉点。在 68 例人类妊娠中对胎盘 Fc 受体丰度、干扰素刺激基因 (ISG) 表达和 SARS-CoV-2 抗体转移进行了研究。母体 SARS-CoV-2 感染后，观察到胎盘 Fc 受体、ISG 和蛋白质以及白细胞介素 10 的性别二态性表达，并且怀有男性胎儿的妊娠个体的胎盘组织中这些特征上调。在怀有男性胎儿的妊娠中还观察到母体 SARS-CoV-2 特异性抗体滴度降低和胎盘抗体转移受损。这些结果证明了胎儿性别特异性的母体和胎盘对 SARS-CoV-2 的适应性和先天免疫反应。