Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19

• Published in: Free radical biology & medicine Vol. 194; pp. 308 - 315
• Main Authors: Pawelzik, Sven-Christian, Arnardottir, Hildur, Sarajlic, Philip, Mahdi, Ali, Vigor, Claire, Zurita, Javier, Zhou, Bingqing, Kolmert, Johan, Galano, Jean-Marie, Religa, Dorota, Durand, Thierry, Wheelock, Craig E., Bäck, Magnus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023; Elsevier; The Authors. Published by Elsevier Inc
• Subjects: Chromatography, Liquid; Coronavirus disease 2019 (COVID-19); COVID-19; Eicosanoids; Eicosanoids - metabolism; Emerging diseases; Emulsions; Endocrinology and metabolism; Erythrocyte oxidative stress; Fatty Acids, Omega-3; Human health and pathology; Humans; Infectious diseases; Inflammation; Isoprostanes; Life Sciences; Oxidative Stress; Pharmaceutical sciences; Pharmacology; Resolution of inflammation; Single-Blind Method; Tandem Mass Spectrometry; Isoprostanes; Eicosanoids; Inflammation; Resolution of inflammation; Erythrocyte oxidative stress; Coronavirus disease 2019 (COVID-19)
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.12.006

Proinflammatory bioactive lipid mediators and oxidative stress are increased in coronavirus disease 2019 (COVID-19). The randomized controlled single-blind trial COVID-Omega-F showed that intravenous omega-3 polyunsaturated fatty acids (n-3 PUFA) shifted the plasma lipid signature of COVID-19 towards increased proresolving precursor levels and decreased leukotoxin diols, associated with a beneficial immunodulatory response. The present study aimed to determine the effects of n-3 PUFA on the urinary oxylipidome and oxidative stress in COVID-19. From the COVID-Omega-F trial, 20 patients hospitalized for COVID-19 had available serial urinary samples collected at baseline, after 24-48 h, and after completing 5 days treatment with one daily intravenous infusion (2 mL/kg) of either placebo (NaCl; n = 10) or a lipid emulsion containing 10 g of n-3 PUFA per 100 mL (n = 10). Urinary eicosanoids and isoprostanes were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Erythrocytes obtained at the different time-points from n = 10 patients (n = 5 placebo and n = 5 n-3 PUFA) were used for determination of reactive oxygen species. Intravenous n-3 PUFA emulsion administration altered eicosanoid metabolites towards decreased levels for mediators of inflammation and thrombosis, and increased levels of the endothelial function mediator prostacyclin. Furthermore, non-enzymatic metabolism was skewed towards n-3 PUFA-derived metabolites with potential anti-inflammatory and pro-resolving effects. The oxidative stress marker 15-F2t-isoprostane was significantly lower in patients receiving n-3 PUFA treatment, who also exhibited significantly decreased erythrocyte oxidative stress compared with placebo-treated patients. These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipin profile and decreased oxidative stress in COVID-19. [Display omitted] •COVID-Omega-F showed beneficial immunomodulatory effects in COVID-19.•Urinary fatty acid metabolites reflect the systemic lipid mediator biosynthesis.•Intravenous omega-3 fatty acids decreased urinary isoprostanes.•Erythrocte reactive oxygen species were lower in omega-3 compared with placebo.•Beneficial effects of n-3 PUFA on the oxylipidome and oxidate stress in COVID-19.