Systems-wide View of Host-Pathogen Interactions Across COVID-19 Severities Using Integrated Omics Analysis

The mechanisms explaining the variability in COVID-19 clinical manifestations (mild, moderate, and severe) are not fully understood. To identify key gene expression markers linked to disease severity, we employed an integrated approach, combining host-pathogen protein-protein interaction data and viral-induced host gene expression data. We analyzed an RNA-seq dataset from peripheral blood mononuclear cells across 12 projects representing the spectrum of disease severity. We identified genes showing differential expression across mild, moderate, and severe conditions. Enrichment analysis of the pathways in host proteins targeted by each of the SARS-CoV-2 proteins revealed a strong association with processes related to ribosomal biogenesis, translation, and translocation. Interestingly, most of these pathways and associated cellular machinery, including ribosomal biogenesis, ribosomal proteins, and translation, were upregulated in mild conditions but downregulated in severe cases. This suggests that COVID-19 exhibits a paradoxical host response, boosting host/viral translation in mild cases but slowing it in severe cases.