Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.
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 articlePermalink
https://hdl.handle.net/10161/22409Published Version (Please cite this version)
10.1038/s41467-021-21289-yPublication 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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Show full item recordScholars@Duke
Thomas Burke
Manager, Systems Project
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
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
Assistant Professor in Biostatistics & Bioinformatics
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
Emily Ray Ko
Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for
infectious disease, hospitalist
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
Micah Thomas McClain
Associate Professor of Medicine
Daniel Raphael Saban
Associate Professor of Ophthalmology
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
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.
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.
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
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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