Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal–fetal interface following SARS-CoV-2 infection

During pregnancy the maternal–fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal–fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal–fetal interface, which may be associated with pregnancy complications. Gao, Mathur, Tam and colleagues characterize transcriptomic and epigenomic alterations at the maternal–fetal interface in patients with COVID-19, thereby providing insights into aberrant pregnancy outcomes associated with SARS-COV-2 infection.