Integrative single-cell transcriptome analysis provides new insights into post-COVID-19 pulmonary fibrosis and potential therapeutic targets.
Yumin KimYeongmin KimHyobin Julianne LimDae-Kyum KimJi-Hwan ParkChang-Myung OhPublished in: Journal of medical virology (2023)
The global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 virus has resulted in a significant number of patients experiencing persistent symptoms, including post-COVID pulmonary fibrosis (PCPF). This study aimed to identify novel therapeutic targets for PCPF using single-cell RNA-sequencing data from lung tissues of COVID-19 patients, idiopathic pulmonary fibrosis (IPF) patients, and a rat transforming growth factor beta-1-induced fibrosis model treated with antifibrotic drugs. Patients with COVID-19 had lower alveolar macrophage counts than healthy controls, whereas patients with COVID-19 and IPF presented with elevated monocyte-derived macrophage counts. A comparative transcriptome analysis showed that macrophages play a crucial role in IPF and COVID-19 development and progression, and fibrosis- and inflammation-associated genes were upregulated in both conditions. Functional enrichment analysis revealed the upregulation of inflammation and proteolysis and the downregulation of ribosome biogenesis. Cholesterol efflux and glycolysis were augmented in both macrophage types. The study suggests that antifibrotic drugs may reverse critical lung fibrosis mediators in COVID-19. The results help clarify the molecular mechanisms underlying pulmonary fibrosis in patients with severe COVID-19 and IPF and highlight the potential efficacy of antifibrotic drugs in COVID-19 therapy. Collectively, all these findings may have significant implications for the development of new treatment strategies for PCPF.
Keyphrases
- pulmonary fibrosis
- sars cov
- idiopathic pulmonary fibrosis
- coronavirus disease
- respiratory syndrome coronavirus
- single cell
- end stage renal disease
- transforming growth factor
- ejection fraction
- newly diagnosed
- oxidative stress
- rna seq
- chronic kidney disease
- adipose tissue
- stem cells
- prognostic factors
- high throughput
- signaling pathway
- cell proliferation
- electronic health record
- high glucose
- machine learning
- peripheral blood
- physical activity
- transcription factor
- dna methylation
- mesenchymal stem cells
- endothelial cells
- climate change
- genome wide
- patient reported
- dendritic cells
- poor prognosis
- depressive symptoms
- stress induced