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Title: Characterization of Altered Gene Expression and Histone Methylation in Peripheral Blood Mononuclear Cells Regulating Inflammation in COVID-19 Patients.

Authors: Yang, Xiaoming; Rutkovsky, Alex C; Zhou, Juhua; Zhong, Yin; Reese, Julian; Schnell, Timothy; Albrecht, Helmut; Owens, William B; Nagarkatti, Prakash S; Nagarkatti, Mitzi

Published In J Immunol, (2022 Apr 15)

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.

PubMed ID: 35379747 Exiting the NIEHS site

MeSH Terms: COVID-19 Drug Treatment*; COVID-19*/genetics; COVID-19*/metabolism; DNA Methylation; Epigenesis, Genetic/physiology; Gene Expression; Histones/metabolism; Humans; Inflammation*/genetics; Inflammation*/metabolism; Leukocytes, Mononuclear*/metabolism; Receptors, Interleukin-1/metabolism; Transcriptome

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