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

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Date
2020-12-05
Authors
Giroux, Nicholas S
Ding, Shengli
McClain, Micah T
Burke, Thomas W
Petzold, Elizabeth
Chung, Hong A
Palomino, Grecia R
Wang, Ergang
Xi, Rui
Bose, Shree
Rotstein, Tomer
Nicholson, Bradly P
Chen, Tianyi
Henao, Ricardo
Sempowski, Gregory D
Denny, Thomas N
Ko, Emily R
Ginsburg, Geoffrey S
Kraft, Bryan D
Tsalik, Ephraim L
Woods, Christopher W
Shen, Xiling
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(22 total)
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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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Journal article
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https://hdl.handle.net/10161/21991
Published Version (Please cite this version)
10.1101/2020.12.04.412155
Publication Info
Giroux, Nicholas S; Ding, Shengli; McClain, Micah T; Burke, Thomas W; Petzold, Elizabeth; Chung, Hong A; ... Shen, Xiling (2020). Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity. bioRxiv. 10.1101/2020.12.04.412155. Retrieved from https://hdl.handle.net/10161/21991.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. He has recently been appointed to the Duke University Fuqua School of Business Health Sector Advisory Council. Previously, he was an Associate Professor of Pathology, Laboratory M
Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Henao

Ricardo Henao

Assistant Professor in Biostatistics & Bioinformatics
Ko

Emily Ray Ko

Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for infectious disease, hospitalist
Kraft

Bryan David Kraft

Adjunct Assistant Professor in the Department of Medicine
Dr. Kraft has a wide variety of clinical and research interests, including sepsis, pneumonia, and acute respiratory distress syndrome (ARDS), and has special expertise in rare lung diseases such as pulmonary fibrosis and pulmonary alveolar proteinosis (PAP). PAP can be congenital, hereditary, autoimmune, or due to occupational exposures (e.g. dusts, fibers, silica). Dr. Kraft performs whole lung lavage (WLL) at Duke in a state-of-the art hyperbaric chamber within the Duke C
Sempowski

Gregory David Sempowski

Professor in Medicine
Dr. Sempowski earned his PhD in Immunology from the University of Rochester and was specifically trained in the areas of inflammation, wound healing, and host response (innate and adaptive).  Dr. Sempowski contributed substantially to the field of lung inflammation and fibrosis defining the roles of pulmonary fibroblast heterogeneity and CD40/CD40L signaling in regulating normal and pathogenic lung inflammation.  During his postdoctoral training with Dr. Barton F. H
Shen

Xiling Shen

Hawkins Family Associate Professor
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 Biolog
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Woods

Christopher Wildrick Woods

Professor of Medicine
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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Alphabetical list of authors with Scholars@Duke profiles.
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