1. Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
- Author
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Matthew S. Kelly, Bradly P. Nicholson, Xiling Shen, Emily M. Ko, Thomas N. Denny, Florica J Constantine, Yiling Liu, Chen Yu, Ricardo Henao, Micah T. McClain, Christopher W. Woods, Bryan Kraft, Daniel R. Saban, Elizabeth Petzold, Geoffrey S. Ginsburg, Gregory D. Sempowski, Thomas W. Burke, Robert Rolfe, Julie M Steinbrink, and Ephraim L. Tsalik
- Subjects
0301 basic medicine ,Letter ,Science ,General Physics and Astronomy ,Disease ,Biology ,Predictive markers ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,Prognostic markers ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Interferon ,Influenza, Human ,Pneumonia, Bacterial ,medicine ,Humans ,Coronavirus ,Multidisciplinary ,SARS-CoV-2 ,Sequence Analysis, RNA ,Gene Expression Profiling ,Bacterial pneumonia ,COVID-19 ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Gene expression profiling ,030104 developmental biology ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Immunology ,Leukocytes, Mononuclear ,Cytokines ,Infectious diseases ,Signal transduction ,Systems biology ,Signal Transduction ,medicine.drug - 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.
- Published
- 2021