Mechanisms and Therapeutic Strategies for Pulmonary Fibrosis Post-COVID-19 ARDS: Insights from Comprehensive Bioinformatics

Background Coronavirus disease 2019 (COVID-19) pandemic has led to numerous cases of acute respiratory distress syndrome (ARDS), with a significant number of survivors developing pulmonary fibrosis as a chronic sequela. This condition poses severe long-term health challenges, significantly burdening public health systems. Despite significant research on the acute phase of COVID-19, the mechanisms underlying pulmonary fibrosis following COVID-19 associated ARDS remain poorly understood, and effective therapies are yet to be established. This study aims to elucidate the molecular mechanisms, identify potential biomarkers, and explore therapeutic options for pulmonary fibrosis post-COVID-19-related ARDS through comprehensive transcriptomic and bioinformatic analyses. Methods We collected datasets from Gene Expression Omnibus (GEO) database, including transcriptional profiles of COVID-19, ARDS, and pulmonary fibrosis. Differentially expressed genes (DEGs) common to these conditions were identified, reflecting the transcriptional landscape of pulmonary fibrosis post-COVID-19 ARDS. Functional and pathway enrichment analyses was conducted. Protein-protein interaction (PPI) network was constructed to determine the hub genes and their regulatory networks. Drugs that interact with hub genes were explored and gene-disease associations were analyzed to identify potential therapeutic strategies. Results We identified 116 common DEGs among COVID-19, ARDS, and pulmonary fibrosis datasets. Functional enrichment highlighted critical processes including inflammatory response, apoptosis, transcription regulation, and MAPK cascade. PPI network revealed hub genes which may play crucial roles in the pathogenesis of pulmonary fibrosis post-COVID-19-related ARDS. Notably, FCER1A, associated with immune response and inflammation, GATA2, involved in macrophage function and erythropoiesis, and CLC, indicative of eosinophil activity, emerged as central players. Regulatory network analysis highlighted significant transcription factors (TFs) and microRNAs (miRNAs) associated with hub genes. We found FDA-approved drugs that could interact with these hub genes, including omalizumab, mizolastine, desloratadine, epoetin alfa, and moxidectin. Gene-disease interaction analysis revealed that diseases caused by GATA2 deficiency and immunodeficiency were associated with hub genes. Conclusion Our findings provide valuable insights into the molecular underpinnings of pulmonary fibrosis post-COVID-19 ARDS and highlight potential biomarkers and therapeutic targets. The repurpose of drugs offers a promising avenue for rapid clinical application, potentially improving outcomes. This study provides ideas for improved treatment for pulmonary fibrosis post-COVID-19 ARDS.