Severe respiratory viral infections: epigenetic mechanisms of predisposition and the possibilities of epigenetically targeted therapy

The emergence of highly pathogenic strains of influenza and coronavirus (CoV) viruses has caused outbreaks of epidemics and pandemics of lung diseases, characterized by severe course and high mortality. One of the main tasks of intensive care is to stratify and minimize the risk of developing multiple organ failure (MOF) in patients during their stay in the intensive care unit (ICU). Epigenetic mechanisms of gene expression control, including DNA and RNA methylation, histone modifications and noncoding RNAs, can be used by viruses to prevent the development of innate and adaptive immunity responses, change the adequacy of the inflammatory response, and thereby contribute to the severe course of pulmonary disease. For example, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and H5N1 influenza virus can interfere with host antigen presentation through DNA methylation and histone modifications. Presumably, the same mechanisms may be involved in patients with coronavirus disease-2019 (COVID-19), in whom tocilizumab epigenetically reduced microvascular damage. Targeting epigenetic pathways of immune modulators (e. g. tocilizumab) or repurposed drugs (e. g. statins) may provide new therapeutic options for controlling host-virus interactions during the development of critical illness. The review provides updated information on epigenetic mechanisms and repurposed drugs that affect epigenetic pathways that may be clinically effective for risk stratification and useful for the treatment of patients with severe respiratory viral infections.