Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derive

This cross-sectional study examined how maternal SARS-CoV-2 infection during pregnancy alters fetal placental macrophage programming, with implications for offspring neurodevelopment. Term placentas were collected from 24 pregnancies at Massachusetts General Hospital (10 SARS-CoV-2�exposed, 14 unexposed controls), and single-cell RNA sequencing was performed on isolated Hofbauer cells (HBCs), fetal placental macrophages that share developmental origins with brain microglia. 8 transcriptionally distinct HBC subpopulations were identified, several of which exhibited SARS-CoV-2�associated, cluster-specific alterations in pathways related to phagocytosis, neuroinflammation, and cellular metabolism. Using HBC-derived microglia-like cells (HBC-iMGs), the study demonstrated reduced synaptosome phagocytosis in SARS-CoV-2�exposed samples, consistent with impaired microglial pruning capacity in this in vitro model. Together, these findings support the use of HBCs as accessible, personalized cellular models to investigate how maternal immune activation shapes fetal brain immune programming and potential neurodevelopmental risk.