COVD-19 infection during pregnancy induces a hematopoietic stem cell signature in cord blood fetal cells. COVD-19 infection during pregnancy induces a hematopoietic stem cell signature in cord blood fetal cells

Pregnant women and their fetuses are particularly susceptible to respiratory pathogens. How they respond to SARS-CoV-2 infection is still under investigation. Here, we studied the transcriptome and phenotype of umbilical cord blood cells in pregnant women infected or not with SARS-CoV-2. We found that symptomatic maternal COVID-19 was associated with a transcriptional erythroid cell signature as compared with asymptomatic and uninfected mothers. We observed an expansion of fetal hematopoietic progenitors skewed towards erythroid differentiation and displaying increased clonogenicity. We found no difference in inflammatory cytokines in the cord blood upon SARS-CoV-2 infection. Interestingly, we showed an activation of hypoxia pathway in cord blood cells from symptomatic COVID-19 mothers, suggesting that maternal hypoxia may be triggering this fetal stress erythropoiesis. Overall, these results show a fetal hematopoietic response to symptomatic COVID-19 in pregnant mothers in the absence of vertically transmitted SARS-CoV-2 infection, which is likely to be a mechanism of fetal adaptation to maternal infection and reduced oxygen supply. Overall design: Comparative differences gene expression in cord blood mononuclear cells between COVID- and asymptomatic COVID+ and severe COVID+

孕妇及其胎儿对呼吸道病原体尤其易感，二者对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的应答机制仍有待进一步探究。本研究针对感染与未感染SARS-CoV-2的孕妇，对其脐带血细胞的转录组与表型展开分析。研究发现，与无症状及未感染孕妇相比，出现症状的孕产妇新冠病毒感染呈现出转录组层面的红细胞特征。我们观察到胎儿造血祖细胞发生扩增，其分化方向偏向红细胞系且克隆形成能力增强。本研究未发现SARS-CoV-2感染后脐带血中炎症细胞因子存在显著差异。值得注意的是，我们发现感染新冠且出现症状的孕妇的脐带血细胞中存在缺氧通路激活现象，提示孕产妇缺氧可能诱发了胎儿的应激性红细胞生成。综上，本研究结果表明，在未发生垂直传播性SARS-CoV-2感染的情况下，胎儿会对孕产妇出现症状的新冠感染产生造血应答，这一机制可能是胎儿对孕产妇感染及氧供减少的适应性反应。实验设计：对比未感染新冠（COVID-）、无症状新冠感染（COVID+）及重症新冠感染孕妇的脐带血单个核细胞的基因表达差异。