Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity.

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Giroux, Nicholas S

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Ding, Shengli

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McClain, Micah T

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Burke, Thomas W

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Petzold, Elizabeth

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Chung, Hong A

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Palomino, Grecia R

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Wang, Ergang

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Xi, Rui

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Bose, Shree

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Rotstein, Tomer

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Nicholson, Bradly P

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Chen, Tianyi

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Henao, Ricardo

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Sempowski, Gregory D

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Denny, Thomas N

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Ko, Emily R

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Ginsburg, Geoffrey S

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Kraft, Bryan D

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Tsalik, Ephraim L

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Woods, Christopher W

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Shen, Xiling

dc.date.accessioned

2021-01-04T20:47:47Z

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2021-01-04T20:47:47Z

dc.date.issued

2020-12-05

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2021-01-04T20:47:38Z

dc.description.abstract

SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects.

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https://hdl.handle.net/10161/21991

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eng

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Cold Spring Harbor Laboratory

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bioRxiv

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10.1101/2020.12.04.412155

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Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity.

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Journal article

duke.contributor.orcid

Henao, Ricardo|0000-0003-4980-845X

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Sempowski, Gregory D|0000-0003-0391-6594

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Ginsburg, Geoffrey S|0000-0003-4739-9808

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Woods, Christopher W|0000-0001-7240-2453

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Shen, Xiling|0000-0002-4978-3531

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School of Medicine

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Duke Human Vaccine Institute

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Duke Global Health Institute

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Medicine, Duke Human Vaccine Institute

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Duke

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Institutes and Centers

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University Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Clinical Science Departments

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Nursing

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Duke Cancer Institute

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Pathology

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Medicine, Cardiology

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School of Nursing

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Medicine, Pulmonary, Allergy, and Critical Care Medicine

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Staff

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Pratt School of Engineering

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Biomedical Engineering

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Electrical and Computer Engineering

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Molecular Genetics and Microbiology

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Pharmacology & Cancer Biology

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Basic Science Departments

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