Integrated Mendelian Randomization and Single-Cell RNA Sequencing Analyses Reveal Lactate Metabolism as a Key Pathway in COVID-19-Induced Pulmonary Fibrosis.

Background: The COVID-19 pandemic has led to a variety of long-term complications, with COVID-19-induced idiopathic pulmonary fibrosis (IPF) becoming a major concern. However, the underlying mechanisms, effective therapeutic strategies, and long-term prognosis of COVID-19-related pulmonary fibrosis remain unclear. Methods: This study utilized Mendelian randomization (MR) analysis and single-cell RNA sequencing (scRNA-seq) to systematically investigate the molecular mechanisms underlying COVID-19-induced pulmonary fibrosis. MR analysis was conducted to assess causal relationships, while scRNA-seq provided detailed insights into the cellular and molecular processes involved in fibrosis. Results: MR analysis revealed a significant association between COVID-19 infection and the development of IPF (OR = 1.15, 95% CI = 1.05-1.25, Conclusion: This study uncovers a critical mechanism by which COVID-19 promotes pulmonary fibrosis through the regulation of lactate metabolism in lung epithelial cells, with SLC16A4 playing a pivotal role. These findings highlight the potential of targeting this metabolic pathway as a therapeutic approach for pulmonary fibrosis, offering new directions for future antifibrotic treatment strategies.