Epigenetic Priming of Inflammatory Genes in COVID-19: Insights into Pathogenesis and Prognosis

The relatively high morbidity and mortality rates of the coronavirus disease 2019 (COVID-19) pandemic,caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), makes understanding specificrisk factors, pathogenesis and identifying effective therapies a top priority [1], [2]. Age is a general riskfactor, though there is high-variance in the clinical course of COVID-19 in middle-aged patients,including mortality rates over 1% among patients in their 50's [3], [2]. Further, more than one quarter ofnon-survivors in a Wuhan study have no co-morbidities [1]. Non-survivors had elevated serum IL-6, andfeatures of acute respiratory distress syndrome (ARDS) [1], [2]. These findings have provided rationalefor initiation of trials to explore therapeutic efficacy of IL-1R and IL-6R blockade in COVID-19 [4]. Instudying epigenetic control of inflammatory genes, we have found that key immune genes in bloodprogenitors are variably regulated by epigenetic poising across individuals, with variability across age anddisease states. Herein, we aim to reveal specific genes, and epigenetic states of these genes, that mayunderlie morbidity and mortality in COVID-19 through use of sensitive epigenomic methods recentlydeveloped by the lab. This work will illuminate features of SARS-CoV-2 susceptibility and pathogenesis,which is of the utmost importance if we are to develop effective therapies and patient managementstrategies in a timely manner.