Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity.
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/10161/21991Published Version (Please cite this version)
10.1101/2020.12.04.412155Publication 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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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, 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. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
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.
Ricardo Henao
Associate Professor in Biostatistics & Bioinformatics
Emily Ray Ko
Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for
infectious disease.
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
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
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 Biolog
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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