Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

• Published in: iScience Vol. 27; no. 1; p. 108288
• Main Authors: McClain, Micah T., Zhbannikov, Ilya, Satterwhite, Lisa L., Henao, Ricardo, Giroux, Nicholas S., Ding, Shengli, Burke, Thomas W., Tsalik, Ephraim L., Nix, Christina, Balcazar, Jorge Prado, Petzold, Elizabeth A., Shen, Xiling, Woods, Christopher W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.01.2024; Elsevier
• Subjects: Components of the immune system; Epigenetics; Health sciences; Immune response; Molecular mechanism of gene regulation; Transcriptomics; Virology; Health sciences; Immune response; Transcriptomics; Epigenetics; Components of the immune system; Molecular mechanism of gene regulation; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108288

To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19. [Display omitted] •Detectable immune response patterns precede clinical events in COVID-19•Clinical decompensation involves conserved immune response elements•Combined genomic approaches offer insights into the biology of COVID-19 Health sciences; Molecular mechanism of gene regulation; Epigenetics; Immune response; Components of the immune system; Virology ; Transcriptomics