Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

dc.contributor.author

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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Rivera, Grecia O

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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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De Ussel, Maria Iglesias

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Satterwhite, Lisa L

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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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Shen, Xiling

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Woods, Christopher W

dc.date.accessioned

2022-08-08T16:43:21Z

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2022-08-08T16:43:21Z

dc.date.issued

2022-07-09

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2022-08-08T16:43:20Z

dc.description.abstract

SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associated with mild or moderate symptoms were already robust and included severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.

dc.identifier

10.1038/s41598-022-15668-8

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2045-2322

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2045-2322

dc.identifier.uri

https://hdl.handle.net/10161/25585

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Scientific reports

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10.1038/s41598-022-15668-8

dc.subject

Leukocytes, Mononuclear

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Chromatin

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Humans

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Immunoglobulin G

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Antiviral Agents

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Severity of Illness Index

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Seroconversion

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COVID-19

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SARS-CoV-2

dc.title

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

dc.type

Journal article

duke.contributor.orcid

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

duke.contributor.orcid

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

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Tsalik, Ephraim L|0000-0002-6417-2042

duke.contributor.orcid

Shen, Xiling|0000-0002-4978-3531

duke.contributor.orcid

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

pubs.begin-page

11714

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1

pubs.organisational-group

Duke

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Pratt School of Engineering

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School of Medicine

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Faculty

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Clinical Science Departments

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Institutes and Centers

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Civil and Environmental Engineering

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Medicine

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Pathology

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Medicine, Duke Human Vaccine Institute

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Medicine, Infectious Diseases

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Medicine, Pulmonary, Allergy, and Critical Care Medicine

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Duke Human Vaccine Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Duke Institute for Brain Sciences

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Duke Center for Applied Genomics and Precision Medicine

pubs.publication-status

Published

pubs.volume

12

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