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

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.

Department

Description

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Citation

Published Version (Please cite this version)

10.1016/j.isci.2023.108288

Publication Info

McClain, Micah T, Ilya Zhbannikov, Lisa L Satterwhite, Ricardo Henao, Nicholas S Giroux, Shengli Ding, Thomas W Burke, Ephraim L Tsalik, et al. (2024). Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection. iScience, 27(1). p. 108288. 10.1016/j.isci.2023.108288 Retrieved from https://hdl.handle.net/10161/31493.

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Scholars@Duke

McClain

Micah Thomas McClain

Associate Professor of Medicine
Shen

Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).

Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health

1. Emerging Infections
2. Global Health
3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics
5. Bioterrorism Preparedness
6. Surveillance for communicable diseases
7. Antimicrobial resistance


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