Yumin Kim 1, Yeongmin Kim 1, Hyobin Julianne Lim 2, Dae-Kyum Kim 2, Ji-Hwan Park 3 4 *, Chang-Myung Oh 1 *
1Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
2Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
3Korea Bioinformation Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
4Department of Bioscience, University of Science and Technology (UST), Daejeon, Republic of Korea.
*Corresponding authors: correspondence to Ji-Hwan Park or Chang-Myung Oh
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.