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

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.; Sempowski, Gregory D.; Denny, Thomas N.; Ginsburg, Geoffrey S.; Woods, Christopher W.

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.