On Potential Association of COVID-19 Infection During Pregnancy and Epigenetic Regulation of Metabolic Pathways in Newborns

Background: The COVID-19 pandemic has highlighted the increased susceptibility of pregnant women to SARS-CoV-2 infection and its short-term consequences for maternal and neonatal health, while the longer-term implications for children remain unclear. Evidence from fetal programming and epigenetic research suggests that inflammatory exposures in utero, including maternal infection, may lead to enduring changes in gene regulation that could influence metabolic and immune health later in life. Methods: We analyzed publicly available bulk and single-cell RNA sequencing (RNA-seq) datasets from cord blood of full-term neonates with and without in utero exposure to maternal SARS-CoV-2 infection. Gene expression data were normalized and examined using a pathwayfocused gene set analysis approach. Applying the Linear Combination Test to curated KEGG and Reactome gene set catalogs, we aim to identify cell-type–specific epigenetic effects and potential alterations in metabolic pathways.