Differential Expression of IFI16, IL-33 and CD55 Link Potential Common Pathogenic Mechanisms for COVID-19 and Ulcerative Colitis.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health and shares several clinical features with ulcerative colitis (UC). However, the existence of a common pathological mechanism between COVID-19 and UC remains uncertain. Additionally, effective treatment strategies for UC patients infected with COVID-19 are not well established. In this study, we investigate the potential shared pathogenesis of UC and COVID-19 and explore possible therapeutic regimens through bioinformatics and systems biology approaches. Methods: Common differentially expressed genes (DEGs) were extracted from the COVID-19 and ulcerative colitis (UC) datasets for functional enrichment, pathway analysis. The EnrichR database was used to predict potential transcription factors (TFs), microRNAs (miRNAs), and related drugs and diseases, enabling the construction of a regulatory network for both conditions. Results: We identified 115 significant common DEGs, with 11 high-confidence hub genes-including IFI16, IL-33, and CD55-implicated in innate immunity and inflammatory regulation. Pathway analysis revealed enrichment in interferon signaling, neutrophil activation, and cytokine-mediated responses. Regulatory network reconstruction highlighted miR-155-5p and transcription factors (eg, STAT1) as key regulators. Drug repurposing efforts prioritized retinoic acid, cyclosporine, and TD-139, which target these shared mechanisms. Conclusion: This study reveals robust molecular commonalities between COVID-19 and UC, highlighting dysregulated immune pathways and regulatory networks as shared mechanisms. We propose novel drug-repurposing candidates supported by network-based evidence, offering potential therapeutic strategies for patients with comorbid COVID-19 and UC.