Epigenetic alterations in the placenta associated with SARS-CoV-2 infection during pregnancy

Histone modifications play a key role in chromatin organization and transcriptional regulatory potential. Previously, reduced levels of trimethylated histone H3K4me3 and acetylated H3K9ac were observed in placentas from women with preeclampsia. Building on these findings, this study investigated whether SARS-CoV-2 infection during pregnancy or at delivery is associated with changes in placental histone modifications. Immunohistochemical staining, exploratory western blot analysis, and qualitative immunofluorescence were performed on placental sections from 60 patients stratified into four groups: women with acute SARS-CoV-2 infection at delivery, women with prior infection during gestation, vaccinated controls, and unvaccinated controls. H3K4me3 levels in the syncytiotrophoblast were significantly reduced in both SARS-CoV-2-exposed groups compared to unvaccinated controls, with the most pronounced reduction observed in women with prior infection during gestation. H3K9ac levels did not differ significantly between groups in any compartment after correction for multiple comparisons. No significant associations were found between SCT H3K4me3 levels and maternal age, gestational age, or birthweight, and a sensitivity analysis excluding cases with additional placental pathologies confirmed the robustness of the findings. As no gene expression profiling was performed, functional or transcriptional consequences of the observed H3K4me3 changes cannot be inferred. These descriptive findings warrant further investigation integrating epigenetic and transcriptomic approaches to clarify their functional relevance for placental biology and pregnancy outcomes.