Host Genetic and Epigenetic Factors in Determining Clinical Outcome of Coronavirus Disease-2019

Abstract

The infection caused by Severe Acute Respiratory Syndrome-Corona Virus 2 (SARS-CoV-2) has rapidly emerged as a serious pandemic, causing substantial morbidity and sometimes mortality with a significant healthcare burden. Unfortunately, Pakistan is among top twenty countries of the world affected by COVID19. The clinical spectrum in COVID-19 is diverse, ranging from mild disease having flu-like symptoms to potentially fatal ARDS, cytokine storm, multiple organ failure and death. Common risk factors associated with severe outcome in COVID-19 infection include male gender, older age and presence of comorbidities such as hypertension, diabetes and cardiovascular disease. Here we reviewed the available literature and report that the underlying mechanisms that account for a broad range of symptoms during respiratory viral infections, that have been well studied in the case of influenza viruses, adenoviruses, SARS-CoV and MERS-CoV, suggest that host genetic and epigenetic factors may also play a significant role in determining susceptibility and clinical outcome in COVID-19 infection. In this review we discuss the potential roles of host genetic factors including cellular receptors for COVID-19, HLA and inflammatory cytokine genes. Based on the SARS-CoV-2 genome and protein-protein interactions map between host and viral proteins we also describe the potential roles of several viral proteins in epigenetic modulation of host inflammatory innate immune response by targeting different cellular pathways particularly NF-κB activation, which may lead to the inflammatory cytokine storm and a severe COVID-19 disease. Investigations of these genetic and epigenetic mechanisms during COVID-19, especially in local settings, will be helpful in management of patients with higher risks and in the development of novel antiviral therapeutics.