Epigenetic susceptibility to severe respiratory viral infections: pathogenic and therapeutic implications: a narrative review

Crimi, Ettore; Benincasa, Giuditta; Figueroa-Marrero, Neisaliz; Galdiero, Massimiliano; Napoli, Claudio

The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) methylation, histone modifications, and non-coding RNAs may lead to perturbations of the host immune-related transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during host–pathogen interaction to interfere with innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. For example, Middle East respiratory syndrome-CoV and H5N1 can affect host antigen presentation through DNA methylation and histone modifications. The same mechanisms would presumably occur in patients with coronavirus disease 2019, in which tocilizumab may epigenetically reduce microvascular damage. Targeting epigenetic pathways by immune modulators (e.g. tocilizumab) or repurposed drugs (e.g. statins) may provide novel therapeutic opportunities to control viral–host interaction during critical illness. In this article, we provide an update on epigenetic-sensitive mechanisms and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and beneficial for treatment of patients affected by severe viral respiratory infections.