DNA methylation changes in infants of mothers with SARS-CoV-2 infection during pregnancy

Maternal environmental exposures, including viral infections, can exert intergenerational effects on the offspring’s epigenome. Herein, based on the Swedish COVID-19 during Pregnancy and Early childhood study (COPE), we explored how mild SARS-CoV-2 infection during pregnancy affected the DNA methylome of peripheral blood mononuclear cells in infants, using Illumina EPIC array. We found significant alterations in DNA methylation patterns in genes related to neurodevelopmental pathways that overlap with cellular processes hijacked by viruses for their own replication. The alterations were further confirmed in cord blood mononuclear cells. Subsequently, we determined the functional consequences of epigenetic rewiring due to maternal SARS-CoV-2 infection without fetal infection and found that fetal exposure to mediators driven by maternal infection, results in an altered responsiveness of the infant’s immune cells upon subsequent cell activation in vitro . Finally, we demonstrate that these functional alterations were linked to the identified DNA methylation changes.