Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes

Characterizing key molecular and cellular pathways involved in COVID-19 is essential for disease prognosis and management. We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity. Specifically, we identify globally dysregulated immune related pathways, such as cytokine-cytokine receptor signaling, complement and coagulation cascades, JAK-STAT, and TGF-beta signaling pathways in all, though to a higher extent in patients with severe symptoms. The excessive release of cytokines and chemokines such as CCL2, CCL22, CXCL9 and CXCL12 and certain interferons and interleukins related genes like IFIH1, IFI44, IFIT1 and IL10 were significantly higher in patients with severe clinical presentation compared to mild and moderate presentations. Differential gene expression analysis identified a small set of regulatory genes that might act as strong predictors of patient outcome. Our data suggest that rapid transcriptome analysis of nasopharyngeal swabs can be a powerful approach to quantify host molecular response and may provide valuable insights into COVID-19 pathophysiology. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Automated summary

Characterizing key molecular and cellular pathways involved in COVID-19 is crucial for disease prognosis and management. Transcriptome analysis of nasopharyngeal swabs of patients revealed dysregulated immune related pathways, especially in patients with severe symptoms, suggesting the excessive release of cytokines and chemokines may contribute to the severity of the disease. Differential gene expression analysis identified a small set of regulatory genes that could act as strong predictors of patient outcome.