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

Micah T. McClain*, Ilya Zhbannikov, Lisa L. Satterwhite, Ricardo Henao, Nicholas S. Giroux, Shengli Ding, Thomas W. Burke, Ephraim L. Tsalik, Christina Nix, Jorge Prado Balcazar, Elizabeth A. Petzold, Xiling Shen, Christopher W. Woods

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number108288
JournaliScience
Volume27
Issue number1
DOIs
StatePublished - Jan 19 2024

Keywords

  • Components of the immune system
  • Epigenetics
  • Health sciences
  • Immune response
  • Molecular mechanism of gene regulation
  • Transcriptomics
  • Virology

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this