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biology, Institut Cochin (U1016 Inserm/UMR8104 CNRS/UMR-S8104)https://www.ebi.ac.uk/ena/browser/view/PRJNA929502Homo sapiensPregnant 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+xref:PubMed:38082066ENAfalseCOVD-19 infection during pregnancy induces a hematopoietic stem cell signature in cord blood fetal cellsCOVD-19 infection during pregnancy induces a hematopoietic stem cell signature in cord blood fetal cells2025-09-242023-08-18PRJNA929502GSE224063960638082066