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

Publication ,  Journal Article
Giroux, NS; Ding, S; McClain, MT; Burke, TW; Petzold, E; Chung, HA; Rivera, GO; Wang, E; Xi, R; Bose, S; Rotstein, T; Nicholson, BP; Chen, T ...
Published in: Res Sq
April 7, 2022

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 associate with mild or moderate symptoms are already robust and include 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 is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish 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.

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Res Sq

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Publication Date

April 7, 2022

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United States
 

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Giroux, N. S., Ding, S., McClain, M. T., Burke, T. W., Petzold, E., Chung, H. A., … Woods, C. (2022). Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion. Res Sq. https://doi.org/10.21203/rs.3.rs-1479864/v1
Giroux, Nicholas S., Shengli Ding, Micah T. McClain, Thomas W. Burke, Elizabeth Petzold, Hong A. Chung, Grecia O. Rivera, et al. “Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.Res Sq, April 7, 2022. https://doi.org/10.21203/rs.3.rs-1479864/v1.
Giroux, Nicholas S., et al. “Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.Res Sq, Apr. 2022. Pubmed, doi:10.21203/rs.3.rs-1479864/v1.
Giroux NS, Ding S, McClain MT, Burke TW, Petzold E, Chung HA, Rivera GO, Wang E, Xi R, Bose S, Rotstein T, Nicholson BP, Chen T, Henao R, Sempowski GD, Denny TN, De Ussel MI, Satterwhite LL, Ko ER, Ginsburg GS, Kraft BD, Tsalik EL, Shen X, Woods C. Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion. Res Sq. 2022 Apr 7;

Published In

Res Sq

DOI

Publication Date

April 7, 2022

Location

United States