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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 17, 2021
- Source ID
- 10.1038/s41467-021-21289-y
Entities
People
- Bradly P. Nicholson
- Bryan Kraft
- Christopher W Woods
- Daniel R. Saban
- Elizabeth Petzold
- Emily M. Ko
- Ephraim L Tsalik
- Florica J. Constantine
- Geoffrey S Ginsburg
- Gregory D Sempowski
- Julie M. Steinbrink
- Matthew S. Kelly
- Micah T McClain
- Ricardo Henao
- Robert Rolfe
- Thomas N. Denny
- Thomas W. Burke
- Xiling Shen
- Yiling Liu
- Yu Chen
Organizations
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense
- United States Department of Veterans Affairs