Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches.

Abstract

In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is 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, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.

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Citation

Published Version (Please cite this version)

10.1101/2020.07.20.20155507

Publication Info

McClain, Micah T, Florica J Constantine, Ricardo Henao, Yiling Liu, Ephraim L Tsalik, Thomas W Burke, Julie M Steinbrink, Elizabeth Petzold, et al. (2020). Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches. medRxiv. 10.1101/2020.07.20.20155507 Retrieved from https://hdl.handle.net/10161/21994.

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Scholars@Duke

Burke

Thomas Burke

Manager, Systems Project
Steinbrink

Julie Steinbrink

Assistant Professor of Medicine

I am a transplant infectious diseases physician. My clinical care focuses on the management of infections in immunocompromised patients, including solid organ and bone marrow transplant recipients, as well as cancer patients. My research focuses on developing noninvasive biomarker diagnostics and severity prognostic tools for infectious diseases in immunocompromised patients.


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