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Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

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Date
2021-02-17
Authors
McClain, Micah T
Constantine, Florica J
Henao, Ricardo
Liu, Yiling
Tsalik, Ephraim L
Burke, Thomas W
Steinbrink, Julie M
Petzold, Elizabeth
Nicholson, Bradly P
Rolfe, Robert
Kraft, Bryan D
Kelly, Matthew S
Saban, Daniel R
Yu, Chen
Shen, Xiling
Ko, Emily M
Sempowski, Gregory D
Denny, Thomas N
Ginsburg, Geoffrey S
Woods, Christopher W
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(20 total)
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Abstract
SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92-0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
Type
Journal article
Permalink
https://hdl.handle.net/10161/22409
Published Version (Please cite this version)
10.1038/s41467-021-21289-y
Publication Info
McClain, Micah T; Constantine, Florica J; Henao, Ricardo; Liu, Yiling; Tsalik, Ephraim L; Burke, Thomas W; ... Woods, Christopher W (2021). Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nature communications, 12(1). pp. 1079. 10.1038/s41467-021-21289-y. Retrieved from https://hdl.handle.net/10161/22409.
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

Burke

Thomas Burke

Manager, Systems Project
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
Kelly

Matthew Kelly

Associate Professor of Pediatrics
My research is broadly focused on elucidating the complex interactions that exist between the host microbiome and exogenous pathogens that cause infections in children. We have several ongoing projects evaluating: 1) the impact of the upper respiratory microbiome on the risk of colonization and invasion by bacterial respiratory pathogens among infants in Botswana; 2) associations between the gut microbiome of pediatric stem cell transplant recipients and the risk of infections (bloodstream infec
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
McClain

Micah Thomas McClain

Associate Professor of Medicine
Saban

Daniel Raphael Saban

Associate Professor of Ophthalmology
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.
Steinbrink

Julie Steinbrink

Assistant Professor of Medicine
I am a transplant infectious diseases physician. My clinical care focuses on the management of infections in immunocompromised patients, including solid organ and bone marrow transplant recipients, as well as cancer patients. My research focuses on developing noninvasive biomarker diagnostics and severity prognostic tools for infectious diseases in immunocompromised patients.
Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
My research is focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation
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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