Metabolic reprogramming of endothelial-related pathways in COVID-19 patients treated with hyperbaric oxygen therapy: a randomized clinical trial

Abstract COVID-19, caused by SARS-CoV-2, is increasingly recognized as a systemic disorder with inflammation, endothelial dysfunction, and metabolic perturbations. This study aimed to characterize metabolic changes in COVID-19 patients undergoing hyperbaric oxygen therapy (HBOT). The clinical trial was registered in EudraCT (2020-002722-90, 3 May 2020), prior to patient enrollment. Thirty hospitalized patients were enrolled and randomized; 28 (14 HBOT and 14 standard care) were included in the present metabolomics analysis. The HBOT group received five sessions at 2.5 ATA for 75 min. Serum metabolites were analyzed using high-resolution LC-MS. Significant changes were observed in metabolites related to arginine/NO metabolism, creatine turnover, phospholipid remodeling, and pterin derivatives. Pathway analysis highlighted the urea cycle, glycerophospholipid remodeling, niacin metabolism, and folate/pterin pathways. HBOT patients showed enhanced metabolic network connectivity. The findings suggest that HBOT induces systemic metabolic adaptations involving amino acid and lipid pathways, as well as redox-related metabolites, which may intersect with vascular and inflammatory regulation. (q < 0.05) (edges = 31 (vs. 10); P < 0.05, |r|>0.5).