DIFFERENTIAL ANALYSIS OF GENE EXPRESSION IN SEVERELY SICK COVID-19 PATIENTS

This study investigates differential gene expression in severely sick COVID-19 patients to elucidate molecular mechanisms driving disease progression. Using transcriptomic data from 44 severe COVID-19 patients and 10 healthy individuals (NCBI GEO: GSE171110), we analyzed whole blood samples via DESeq2, identifying 737 differentially expressed genes (DEGs). Of these, 662 were upregulated (e.g., inflammatory and antiviral pathways) and 75 downregulated. Principal component analysis (PCA) and heatmaps revealed distinct transcriptional signatures between groups, highlighting immune dysregulation. Key upregulated pathways included Jak-STAT, MAPK, PI3K-Akt, Toll-like receptor, and TNF signaling, associated with cytokine storms, neutrophil activation, and oxidative stress. MHC class I genes (linked to CD8+ T-cell and NK-cell cytotoxicity) were elevated, while MHC class II (involved in CD4+ T-cell cytokine production) was suppressed. Pro-inflammatory interleukins (IL-1β, IL-6, IL-12) and antiviral IFN-β were also upregulated, indicating heightened inflammation and antiviral responses. Conversely, DNA repair pathways were disrupted. The findings suggest severe COVID-19 involves hyperactivation of innate immunity and cytotoxic T-cell responses, coupled with impaired adaptive immunity (reduced CD4+ T-cell function). These mechanisms may contribute to tissue damage and cytokine release syndrome (CRS).The study highlights the role of transcriptional dysregulation in driving severe disease outcomes, providing insights into potential therapeutic targets for immune response modulation.