Background: PCPF is a notable post-infection complication of Covid-19 that causes significant morbidity and mortality. Despite the severity, a subset of patients with PCPF have shown improvement, highlighting the need to investigate the underlying mechanisms. In this study, we used BAL samples to look into its molecular basis at the transcriptional level.

Methods: Bronchoscopy was performed as per the standard guidelines and BAL samples were collected from PCPF (n=3) and non-ILD controls (n=3). RNA was isolated from all the samples and subjected to quality check (QC). RNA- sequencing was performed and raw data were processed for quality control, adaptor trimming, and used GRCh38 and SAR-CoV-2 genome for read alignment followed by DEG and functional enrichment analysis.

Results: Using threshold of log2FC >2< and FDR cutoff of 0.1, we identified 4374 differentially expressed genes (594 upregulated, 3780 downregulated), with no alignment to SAR-CoV-2 genome. Cytokine-related genes, including those interacting with viral proteins and receptors, were among the most significant, along with novel coding and non-coding transcripts. Processes related to immune cell chemotaxis, cell cycle, and chemokine receptor binding were prominent. Pathway analysis revealed strong associations with cell cycle, chemokine signaling, viral protein interactions, cytokine receptors, KRAS signaling, and epithelial-to-mesenchymal transition pathways.

Conclusion: The study identifies molecular mechanisms of PCPF, including DEGs and cellular pathways as well as biological processes and functions, offering potential therapeutic targets and enhancing our understanding of its pathogenesis.