GENOMIC ANALYSIS OF PULMONARY FIBROSIS PROGRESSION IN ATHLETES WITH SILICOSIS POST-COVID-19 INFECTION

Abstract

Background: Silicosis, a chronic lung disease caused by exposure to silica dust, is prevalent in sports settings associated with sandstone, ceramics, and other silica-rich environments. Athletes engaged in such sports are at risk of developing silicosis, which can progress silently but severely impairs respiratory function, manifesting as difficulty breathing, coughing, and potentially leading to complications like cor pulmonale. The recent COVID-19 pandemic has exacerbated these challenges, as patients with silicosis are more prone to severe outcomes from the virus, including enhanced pulmonary fibrosis. Objective: This study aims to unravel the genetic underpinnings that exacerbate pulmonary fibrosis in silicosis patients post-COVID-19 infection, with a focus on identifying key pathways and genes involved, using athletes as a contextual framework. Methods: Using R software, we analyzed monocyte gene expression from severe COVID-19 patients and healthy controls, along with silicosis models, from public datasets. Homologous gene conversion was applied to identify common genes, followed by gene ontology and pathway enrichment analyses. The STRING database was utilized for protein-protein interaction analyses, pinpointing central proteins that potentially drive fibrosis in silicosis affected by COVID-19. Results: Analysis revealed significant differentially expressed genes, with a focus on 170 downregulated genes shared across datasets. Functional analysis highlighted critical pathways including lysosome and porphyrin metabolism disruptions. Notably, AP1B1 and AP1S2 emerged as central genes, with potential therapeutic targeting by Agalsidase beta to modulate these effects. Conclusion: Our findings suggest that the exacerbation of pulmonary fibrosis in athletes with silicosis following COVID-19 infection can be attributed to specific genetic disruptions, particularly within lysosomal pathways. This knowledge can guide targeted therapeutic strategies, potentially involving Agalsidase beta, to mitigate fibrosis progression and improve respiratory outcomes for athletes exposed to silica dust. Further research is necessary to validate these findings and optimize treatment protocols tailored for the athletic population.