Abstract
The pandemic of COVID-19 has caused >5 million deaths in the world. One of the leading causes of the severe form of COVID-19 is the production of massive amounts of proinflammatory cytokines. Epigenetic mechanisms, such as histone/DNA methylation, miRNA, and long noncoding RNA, are known to play important roles in the regulation of inflammation. In this study, we investigated if hospitalized COVID-19 patients exhibit alterations in epigenetic pathways in their PBMCs. We also compared gene expression profiles between healthy controls and COVID-19 patients. Despite individual variations, the expressions of many inflammation-related genes, such as arginase 1 and IL-1 receptor 2, were significantly upregulated in COVID-19 patients. We also found the expressions of coagulation-related genes Von Willebrand factor and protein S were altered in COVID-19 patients. The expression patterns of some genes, such as IL-1 receptor 2, correlated with their histone methylation marks. Pathway analysis indicated that most of those dysregulated genes were in the TGF-β, IL-1b, IL-6, and IL-17 pathways. A targeting pathway revealed that the majority of those altered genes were targets of dexamethasone, which is an approved drug for COVID-19 treatment. We also found that the expression of bone marrow kinase on chromosome X, a member of TEC family kinases, was increased in the PBMCs of COVID-19 patients. Interestingly, some inhibitors of TEC family kinases have been used to treat COVID-19. Overall, this study provides important information toward identifying potential biomarkers and therapeutic targets for COVID-19 disease.
【초록키워드】 COVID-19, Dexamethasone, Treatment, Inflammation, Cytokines, IL-6, miRNA, Pathway analysis, COVID-19 disease, Bone marrow, COVID-19 treatment, von Willebrand factor, death, pathway, PBMC, target, targets, mechanisms, variations, receptor, proinflammatory cytokines, inhibitor, information, expression, Epigenetic, IL-1, arginase, protein S, therapeutic targets, COVID-19 patients, Methylation, hospitalized COVID-19 patient, histone, TGF-β, Potential biomarker, Analysis, PBMCs, Gene expression profiles, Pathways, therapeutic target, IL-17, kinases, Regulation, long noncoding RNA, hospitalized COVID-19 patients, chromosome, healthy control, alteration, healthy controls, treat, potential biomarkers, member, IL-1B, gene expression profile, expression patterns, expression pattern, kinase, pandemic of COVID-19, expressions, Genes, caused, significantly, indicated, investigated, approved, provide, majority, correlated, cause, upregulated, dysregulated, histone methylation, TEC, was increased, 【제목키워드】 COVID-19, characterization, peripheral, Regulating, Altered,