Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.
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.
Denny, Thomas Norton
Ginsburg, Geoffrey Steven
Kraft, Bryan David
McClain, Micah Thomas
Saban, Daniel Raphael
Sempowski, Gregory David
McClain, MT; Constantine, FJ; Henao, R; Liu, Y; Tsalik, EL; Burke, TW; Steinbrink, JM; Petzold, E; Nicholson, BP; Rolfe, R; Kraft, BD; Kelly, MS; Saban, DR; Yu, C; Shen, X; Ko, EM; Sempowski, GD; Denny, TN; Ginsburg, GS; Woods, CW
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