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Nature communications
02 17, 2021;12 (1): 1079.

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

Micah T McClain, Florica J Constantine, Ricardo Henao, Yiling Liu, Ephraim L Tsalik, Thomas W Burke, Julie M Steinbrink, Elizabeth Petzold, Bradly P Nicholson, Robert Rolfe, Bryan D Kraft, Matthew S Kelly, Daniel R Saban, Chen Yu, Xiling Shen, Emily M Ko, Gregory D Sempowski, Thomas N Denny, Geoffrey S Ginsburg, Christopher W Woods
Author Information
  1. Micah T McClain: Durham Veterans Affairs Medical Center, Durham, NC, USA. micah.mcclain@duke.edu. ORCID
  2. Florica J Constantine: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  3. Ricardo Henao: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  4. Yiling Liu: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  5. Ephraim L Tsalik: Durham Veterans Affairs Medical Center, Durham, NC, USA.
  6. Thomas W Burke: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  7. Julie M Steinbrink: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  8. Elizabeth Petzold: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  9. Bradly P Nicholson: Institute for Medical Research, Durham, NC, USA.
  10. Robert Rolfe: Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
  11. Bryan D Kraft: Durham Veterans Affairs Medical Center, Durham, NC, USA.
  12. Matthew S Kelly: Duke University Medical Center, Durham, NC, USA.
  13. Daniel R Saban: Department of Opthalmology, Duke University School of Medicine, Durham, NC, USA.
  14. Chen Yu: Department of Opthalmology, Duke University School of Medicine, Durham, NC, USA.
  15. Xiling Shen: Center for Genomics and Computational Biology, Duke University, Durham, NC, USA.
  16. Emily M Ko: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  17. Gregory D Sempowski: Duke Human Vaccine Institute, Durham, NC, USA.
  18. Thomas N Denny: Duke Human Vaccine Institute, Durham, NC, USA.
  19. Geoffrey S Ginsburg: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  20. Christopher W Woods: Durham Veterans Affairs Medical Center, Durham, NC, USA.
PMID: 33597532 DOI: 10.1038/s41467-021-21289-y

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.

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Grants

  1. UM1 AI104681/NIAID NIH HHS
  2. UC6 AI058607/NIAID NIH HHS
  3. K08 HL130557/NHLBI NIH HHS
  4. T32 AI100851/NIAID NIH HHS
  5. U01 AI066569/NIAID NIH HHS
  6. 75N93019C00015/NIAID NIH HHS

MeSH Term

COVID-19
Cytokines
Gene Expression Profiling
Host-Pathogen Interactions
Humans
Influenza, Human
Leukocytes, Mononuclear
Pneumonia, Bacterial
SARS-CoV-2
Sequence Analysis, RNA
Signal Transduction
Transcriptome

Chemicals

Cytokines
Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

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