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

2021-03-01T17:24:46Z

2021-03-01T17:24:46Z

2021-02-17

2021-03-01T17:24:45Z

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.

10.1038/s41467-021-21289-y

2041-1723

2041-1723

https://hdl.handle.net/10161/22409

eng

Springer Science and Business Media LLC

Nature communications

10.1038/s41467-021-21289-y

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

Journal article

Henao, Ricardo|0000-0003-4980-845X

Tsalik, Ephraim L|0000-0002-6417-2042

Burke, Thomas W|0000-0003-0592-5822

Steinbrink, Julie M|0000-0003-0771-3647

Kelly, Matthew S|0000-0001-8819-2315

Shen, Xiling|0000-0002-4978-3531

Sempowski, Gregory D|0000-0003-0391-6594

Ginsburg, Geoffrey S|0000-0003-4739-9808

Woods, Christopher W|0000-0001-7240-2453

1079

1

School of Medicine

Duke Human Vaccine Institute

Duke Global Health Institute

Medicine, Duke Human Vaccine Institute

Duke

Institutes and Centers

University Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Clinical Science Departments

Medicine, Infectious Diseases

Pathology

Medicine, Pulmonary, Allergy, and Critical Care Medicine

Pediatrics, Infectious Diseases

Pediatrics

Published

12