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

Publication ,  Journal Article
McClain, MT; Constantine, FJ; Henao, R; Liu, Y; Tsalik, EL; Burke, TW; Steinbrink, JM; Petzold, E; Nicholson, BP; Rolfe, R; Kraft, BD; Yu, C ...
Published in: Nat Commun
February 17, 2021
Published version (DOI) Open Access Copy (Duke) Link to item

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.

Duke Scholars

Micah Thomas McClain
Author Micah Thomas McClain Medicine, Infectious Diseases
Ricardo Henao
Author Ricardo Henao Biostatistics & Bioinformatics, Division of Translational Bi ...
Ephraim Tsalik
Author Ephraim Tsalik Medicine, Infectious Diseases
Thomas Burke
Author Thomas Burke  
Julie Steinbrink
Author Julie Steinbrink Medicine, Infectious Diseases
Bryan David Kraft
Author Bryan David Kraft Medicine, Pulmonary, Allergy, and Critical Care Medicine
Matthew Kelly
Author Matthew Kelly Pediatrics, Infectious Diseases
Daniel Raphael Saban
Author Daniel Raphael Saban Ophthalmology, Corneal Diseases
Xiling Shen
Author Xiling Shen Pathology
Emily Ray Ko
Author Emily Ray Ko Medicine, General Internal Medicine
Thomas Norton Denny
Author Thomas Norton Denny Medicine, Duke Human Vaccine Institute
Geoffrey Steven Ginsburg
Author Geoffrey Steven Ginsburg Medicine, Cardiology
Christopher Wildrick Woods
Author Christopher Wildrick Woods Medicine, Infectious Diseases
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Published In

Nat Commun

DOI

10.1038/s41467-021-21289-y

EISSN

2041-1723

Publication Date

February 17, 2021

Volume

12

Issue

1

Start / End Page

1079

Location

England

Related Subject Headings

  • Transcriptome
  • Signal Transduction
  • Sequence Analysis, RNA
  • SARS-CoV-2
  • Pneumonia, Bacterial
  • Leukocytes, Mononuclear
  • Influenza, Human
  • Humans
  • Host-Pathogen Interactions
  • Gene Expression Profiling
 

Citation

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MLA
NLM
McClain, M. T., Constantine, F. J., Henao, R., Liu, Y., Tsalik, E. L., Burke, T. W., … Woods, C. W. (2021). Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nat Commun, 12(1), 1079. https://doi.org/10.1038/s41467-021-21289-y
McClain, Micah T., Florica J. Constantine, Ricardo Henao, Yiling Liu, Ephraim L. Tsalik, Thomas W. Burke, Julie M. Steinbrink, et al. “Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.” Nat Commun 12, no. 1 (February 17, 2021): 1079. https://doi.org/10.1038/s41467-021-21289-y.
McClain MT, Constantine FJ, Henao R, Liu Y, Tsalik EL, Burke TW, et al. Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nat Commun. 2021 Feb 17;12(1):1079.
McClain, Micah T., et al. “Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.” Nat Commun, vol. 12, no. 1, Feb. 2021, p. 1079. Pubmed, doi:10.1038/s41467-021-21289-y.
McClain MT, Constantine FJ, Henao R, Liu Y, Tsalik EL, Burke TW, Steinbrink JM, Petzold E, Nicholson BP, Rolfe R, Kraft BD, Kelly MS, Saban DR, Yu C, Shen X, Ko EM, Sempowski GD, Denny TN, Ginsburg GS, Woods CW. Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nat Commun. 2021 Feb 17;12(1):1079.

Published In

Nat Commun

DOI

10.1038/s41467-021-21289-y

EISSN

2041-1723

Publication Date

February 17, 2021

Volume

12

Issue

1

Start / End Page

1079

Location

England

Related Subject Headings

  • Transcriptome
  • Signal Transduction
  • Sequence Analysis, RNA
  • SARS-CoV-2
  • Pneumonia, Bacterial
  • Leukocytes, Mononuclear
  • Influenza, Human
  • Humans
  • Host-Pathogen Interactions
  • Gene Expression Profiling