Epigenetic Activation of Antiviral Sensors and Effectors of Interferon Response Pathways During SARS-CoV-2 Infection

Background: Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear.Methods: We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations to identify casual interactions of blood cells’ methylome in pathology of the COVID-19 disease.Findings: We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from the upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized.Interpretation: The DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers useful in disease management but also present a potential treatment target.Funding: Polish National Agency for Academic Exchange and European Regional Development Fund of the West Pomeranian Province.Declaration of Interest: The authors declare that they have no competing interests.Ethical Approval: Written consent was obtained from all participants from Polish cohort before enrollment. All procedures were in accordance with the ethical standards approved by the Bioethics Committee of the Pomeranian University, Szczecin, with approval number KB-0012/101/2020 -A