CompCorona: A Web Application for Comparative Transcriptome Analyses of 2 Coronaviruses Reveals SARS-Cov2 Specific Host Response

Background/aim: Understanding the mechanism of host transcriptomic response to infection by the SARS-CoV-2 virus is crucial, especially for patients suffering from long-term effects of COVID-19, such as long COVID or pericarditis inflammation, potentially linked to side effects of the SARS-CoV-2 spike proteins. We conducted comprehensive transcriptome and enrichment analyses on lung and peripheral blood mononuclear cells (PBMC) infected SARS-CoV-2, as well as on SARS-CoV and MERS-CoV, to uncover shared pathways and elucidate their common disease progression and viral replication mechanisms.

Materials and methods: We developed CompCorona, the first interactive online tool for visualizing genes response variance among the Coronaviridae family through 2D and 3D principal component analyses (PCA) and exploring systems biology variance using pathway plots. We also made pre-processed datasets of lung and PBMC infected by SARS-CoV-2, SARS-CoV, and MERS-CoV publicly available through CompCorona.

Results:  One remarkable finding in the lung and PBCM datasets infected by SARS-CoV-2, but not in those infected by other coronaviruses (CoVs), is the significant down-regulation of angiogenin (ANG) and vascular endothelial growth factor A (VEGFA) genes, both directly involved in epithelial and vascular endothelial cell dysfunction.  There was also observed suppression of the TNF signaling pathway in cells infected by SARS-CoV-2, along with simultaneous activation of complement and coagulation cascades and pertussis pathways. The ribosome pathway was found to be universally suppressed across all three viruses.  

The online tool CompCorona enables the comparative analysis of 9 pre-processed host transcriptome datasets from cells infected by CoVs, revealing the specific host response differences in cases of SARS-CoV-2 infection. This includes identifying markers of epithelial dysfunction via interactive 2D and 3D PCA, Venn diagrams, and pathway plots.

Conclusion: Our findings suggest that infection by SARS-CoV-2 might induce pulmonary epithelial dysfunction, a phenomenon not observed in cells infected by other CoVs. The publicly available CompCorona tool, along with the pre-processed datasets of cells infected by various CoVs, offers a valuable resource for further research into CoV-associated syndromes.