Host transcriptional response to SARS-CoV-2 infection in COVID-19 patients

Abstract

Background: One of the most perplexing aspects of infection with the SARS-CoV-2 virus has been the variable response elicited in its human hosts. Investigating the transcriptional changes in individuals affected by COVID-19 can help understand and predict the degree of illness and guide clinical outcomes in diverse backgrounds. Methods: Analysis of host transcriptome variations via RNA sequencing from naso/oropharyngeal swabs of COVID-19 patients. Results: We report strong upregulation of the innate immune response, especially type I interferon pathway, upon SARS-CoV-2 infection. Upregulated genes were subjected to a comparative meta-analysis using global datasets to identify a common network of interferon stimulated and viral response genes that mediate the host response and resolution of infection. A large proportion of mis-regulated genes showed a reduction in expression level, suggesting an overall decrease in host mRNA production. Significantly downregulated genes included those encoding olfactory, taste and neuro-sensory receptors. Many pro-inflammatory markers and cytokines were also downregulated or remained unchanged in the COVID-19 patients. Finally, a large number of non-coding RNAs were identified as down-regulated, with a few of the lncRNAs associated with functional roles in directing the response to viral infection. Conclusions: SARS-CoV-2 infection results in the robust activation of the innate immunity. Reduction of gene expression is well correlated with the clinical manifestations and symptoms of COVID-19 such as the loss of smell and taste, and myocardial and neurological complications. This study provides a critical dataset of genes that will enhance our understanding of the nature and prognosis of COVID-19.

Genomic Biomarker Heterogeneities Between SARS-CoV-2 and COVID-19

“…In this section, we use additional twelve datasets to cross-validate the genes identified in Section 3. These datasets include GSE152641 37 , GSE155454 38 , 39 , GSE166190 40 , GSE166253 41 , GSE166530 42 , GSE177477 43 , GSE179448 44 , GSE184401 45 , GSE189039 46;47 , GSE190680 48 , and GSE201530 47;49 .…”

The current status of gene expression profilings in COVID‐19 patients

“…Besides detecting fragments of viral RNA, genome‐wide transcriptomic analysis of the host (i.e., COVID‐19 patients) can be performed. For example, by comparing RNA‐seq data generated from naso/oropharyngeal swabs of 36 COVID‐19 Indian patients hospitalized during the first surge of COVID‐19 to those of 5 COVID‐19 negative control samples, 251 up‐ and 9 068 down‐regulated genes were identified at the threshold of two‐fold changes and adjusted p ‐value < .05 17 . The differentially expressed genes include up‐regulation of genes involved in innate immune response (e.g., interferon signalling, response to virus) and down‐regulation of genes involved in membrane potentials and neurotransmitter transport as well as cardiac, muscular, and neurological processes, suggesting that significant down‐regulation of host transcriptomes can be monitored via nasal swabs.…”