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 specific risk factors, pathogenesis and identifying effective therapies a top priority [1], [2]. Age is a general risk factor, 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 of non-survivors in a Wuhan study have no co-morbidities [1]. Non-survivors had elevated serum IL-6, and features of acute respiratory distress syndrome (ARDS) [1], [2]. These findings have provided rationale for initiation of trials to explore therapeutic efficacy of IL-1R and IL-6R blockade in COVID-19 [4]. In studying epigenetic control of inflammatory genes, we have found that key immune genes in blood progenitors are variably regulated by epigenetic poising across individuals, with variability across age and disease states. Herein, we aim to reveal specific genes, and epigenetic states of these genes, that may underlie morbidity and mortality in COVID-19 through use of sensitive epigenomic methods recently developed 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 management strategies in a timely manner.
Identification of epigenetic ?poising? at inflammatory genes and of specific epigenomic features in blood progenitors or monocytes that correspond to COVID-19 disease course may provide mechanistic insights, therapeutic targets, and prognostic indicators in COVID-19 disease. Further, this information could be the basis of new prognostic clinical assays that direct experimental therapies.
