tetano
Editor, Senior Moderator
Nat Commun
. 2021 Feb 17;12(1):1079.
doi: 10.1038/s41467-021-21289-y.
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
Micah T McClain[SUP] 1 2 3 [/SUP], Florica J Constantine[SUP] 4 [/SUP], Ricardo Henao[SUP] 4 [/SUP], Yiling Liu[SUP] 4 [/SUP], Ephraim L Tsalik[SUP] 5 4 6 [/SUP], Thomas W Burke[SUP] 4 [/SUP], Julie M Steinbrink[SUP] 4 6 [/SUP], Elizabeth Petzold[SUP] 4 [/SUP], Bradly P Nicholson[SUP] 7 [/SUP], Robert Rolfe[SUP] 6 [/SUP], Bryan D Kraft[SUP] 5 4 8 [/SUP], Matthew S Kelly[SUP] 8 [/SUP], Daniel R Saban[SUP] 9 [/SUP], Chen Yu[SUP] 9 [/SUP], Xiling Shen[SUP] 10 [/SUP], Emily M Ko[SUP] 4 [/SUP], Gregory D Sempowski[SUP] 11 [/SUP], Thomas N Denny[SUP] 11 [/SUP], Geoffrey S Ginsburg[SUP] 4 [/SUP], Christopher W Woods[SUP] 5 4 6 [/SUP]
Affiliations
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.
. 2021 Feb 17;12(1):1079.
doi: 10.1038/s41467-021-21289-y.
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
Micah T McClain[SUP] 1 2 3 [/SUP], Florica J Constantine[SUP] 4 [/SUP], Ricardo Henao[SUP] 4 [/SUP], Yiling Liu[SUP] 4 [/SUP], Ephraim L Tsalik[SUP] 5 4 6 [/SUP], Thomas W Burke[SUP] 4 [/SUP], Julie M Steinbrink[SUP] 4 6 [/SUP], Elizabeth Petzold[SUP] 4 [/SUP], Bradly P Nicholson[SUP] 7 [/SUP], Robert Rolfe[SUP] 6 [/SUP], Bryan D Kraft[SUP] 5 4 8 [/SUP], Matthew S Kelly[SUP] 8 [/SUP], Daniel R Saban[SUP] 9 [/SUP], Chen Yu[SUP] 9 [/SUP], Xiling Shen[SUP] 10 [/SUP], Emily M Ko[SUP] 4 [/SUP], Gregory D Sempowski[SUP] 11 [/SUP], Thomas N Denny[SUP] 11 [/SUP], Geoffrey S Ginsburg[SUP] 4 [/SUP], Christopher W Woods[SUP] 5 4 6 [/SUP]
Affiliations
- 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.