Genome‐wide DNA methylation profiling of peripheral blood reveals an epigenetic signature associated with severe COVID‐19
Autor: | Thomas A. Premeaux, Leonel Torres, Kush Dody, Alina P.S. Pang, Jonah B. Sacha, Philip A. Mudd, Nikita S. Iyer, Michael J. Peluso, Yaron Bram, Steven G. Deeks, Robert E. Schwartz, Stephen T. Yeung, Timothy J. Henrich, Bruce K. Patterson, Vasuretha Chandar, Lishomwa C. Ndhlovu, Alain C. Borczuk, Michael J. Corley, Harish Seethamraju |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Immunology Viremia HIV Infections Disease Biology IFN Peripheral blood mononuclear cell SARS‐CoV‐2 Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Immune system COVID‐19 Influenza Human medicine Humans Immunology and Allergy Epigenetics Gene DNA methylation epigenetics Genome Human SARS-CoV-2 dNaM COVID-19 Cell Biology medicine.disease 030104 developmental biology Highlighted Article 030220 oncology & carcinogenesis |
Zdroj: | Journal of Leukocyte Biology |
ISSN: | 1938-3673 0741-5400 |
DOI: | 10.1002/jlb.5hi0720-466r |
Popis: | The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a highly pathogenic RNA virus causing coronavirus disease 2019 (COVID‐19) in humans. Although most patients with COVID‐19 have mild illness and may be asymptomatic, some will develop severe pneumonia, acute respiratory distress syndrome, multi‐organ failure, and death. RNA viruses such as SARS‐CoV‐2 are capable of hijacking the epigenetic landscape of host immune cells to evade antiviral defense. Yet, there remain considerable gaps in our understanding of immune cell epigenetic changes associated with severe SARS‐CoV‐2 infection pathology. Here, we examined genome‐wide DNA methylation (DNAm) profiles of peripheral blood mononuclear cells from 9 terminally‐ill, critical COVID‐19 patients with confirmed SARS‐CoV‐2 plasma viremia compared with uninfected, hospitalized influenza, untreated primary HIV infection, and mild/moderate COVID‐19 HIV coinfected individuals. Cell‐type deconvolution analyses confirmed lymphopenia in severe COVID‐19 and revealed a high percentage of estimated neutrophils suggesting perturbations to DNAm associated with granulopoiesis. We observed a distinct DNAm signature of severe COVID‐19 characterized by hypermethylation of IFN‐related genes and hypomethylation of inflammatory genes, reinforcing observations in infection models and single‐cell transcriptional studies of severe COVID‐19. Epigenetic clock analyses revealed severe COVID‐19 was associated with an increased DNAm age and elevated mortality risk according to GrimAge, further validating the epigenetic clock as a predictor of disease and mortality risk. Our epigenetic results reveal a discovery DNAm signature of severe COVID‐19 in blood potentially useful for corroborating clinical assessments, informing pathogenic mechanisms, and revealing new therapeutic targets against SARS‐CoV‐2. Graphical Abstract A distinct epigenetic signature associated with severe COVID‐19 exists in blood and is potentially useful for corroborating clinical assessments, informing pathogenic mechanisms, and revealing new therapeutic targets. |
Databáze: | OpenAIRE |
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