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

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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.
Original languageEnglish (US)
JournalNature Communications
Issue number1
StatePublished - Dec 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Chemistry
  • General Physics and Astronomy


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