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

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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Published Version (Please cite this version)

10.1038/s41467-021-21289-y

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. (2021). Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nature communications, 12(1). p. 1079. 10.1038/s41467-021-21289-y Retrieved from https://hdl.handle.net/10161/22409.

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