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Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.
McClain, Micah T; Constantine, Florica J; Henao, Ricardo; Liu, Yiling; Tsalik, Ephraim L; Burke, Thomas W; Steinbrink, Julie M; Petzold, Elizabeth; Nicholson, Bradly P; Rolfe, Robert; Kraft, Bryan D; Kelly, Matthew S; Saban, Daniel R; Yu, Chen; Shen, Xiling; Ko, Emily M; Sempowski, Gregory D; Denny, Thomas N; Ginsburg, Geoffrey S; Woods, Christopher W.
  • McClain MT; Durham Veterans Affairs Medical Center, Durham, NC, USA. micah.mcclain@duke.edu.
  • Constantine FJ; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA. micah.mcclain@duke.edu.
  • Henao R; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA. micah.mcclain@duke.edu.
  • Liu Y; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Tsalik EL; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Burke TW; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Steinbrink JM; Durham Veterans Affairs Medical Center, Durham, NC, USA.
  • Petzold E; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Nicholson BP; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
  • Rolfe R; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Kraft BD; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Kelly MS; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
  • Saban DR; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Yu C; Institute for Medical Research, Durham, NC, USA.
  • Shen X; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
  • Ko EM; Durham Veterans Affairs Medical Center, Durham, NC, USA.
  • Sempowski GD; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA.
  • Denny TN; Duke University Medical Center, Durham, NC, USA.
  • Ginsburg GS; Duke University Medical Center, Durham, NC, USA.
  • Woods CW; Department of Opthalmology, Duke University School of Medicine, Durham, NC, USA.
Nat Commun ; 12(1): 1079, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1087444
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Leukocytes, Mononuclear / Sequence Analysis, RNA / Gene Expression Profiling / Transcriptome / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21289-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Leukocytes, Mononuclear / Sequence Analysis, RNA / Gene Expression Profiling / Transcriptome / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21289-y