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), 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
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.
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
My broad research interests are the cellular and molecular mechanisms that contribute
to pathogenic immunity in ophthalmic disease and vision loss. My studies are currently
focused on dendritic cells (DC), a unique leukocyte population of antigen presenting
cells required for both initiating and determining the type of immune response generated.
These cells contribute to the maintenance of health versus immunity in ocular disease.
I am currently investigating the r
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
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 at Duke has 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 pre
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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