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Epigenetic and transcriptomic remodeling in monocytes of severe COVID-19 patients mirrors systemic changes in cytokines and immune cell crosstalk

ABSTRACT: COVID-19 manifests with a wide spectrum of clinical phenotypes ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by a marked dysregulation in the myeloid compartment, especially monocytes; however, little is known about the epigenetic regulation of these cells in relation to hyperinflammatory responses in severe COVID-19 patients. In this study, we obtained the DNA methylome and transcriptome of monocytes from severe COVID-19 patients. We observed drastic DNA methylation changes encompassing impairment of type-I interferons (IFN), antigen presentation functions among others, in concordance with gene expression changes supporting the relevance of DNA methylation alterations in the dysregulation of the myeloid compartment. These changes were similar to those occurring in bacterial sepsis, although specific functions resulting from viral infection were also identified. Also, a progressive relationship of DNA methylation alterations and Sequential Organ Failure Assessment (SOFA) score was found related with IFNγ production and T-helper 1 cell cytokine production. Analysis of the single cell transcriptomes of other immune cell types allowed inferring dysregulation of communication between monocytes and other cell types like NK cells, plasma B cells and T cells, which can partly explain monocyte epigenome dysregulation, perpetuating a dysregulated response in these patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE188573 | GEO | 2022/11/01

REPOSITORIES: GEO

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