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.

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.