MS-based targeted profiling of oxylipins in COVID-19: A new insight into inflammation regulation

• Published in: Free radical biology & medicine 2022-02, Vol.180, p.236-243
• Main Authors: Biagini, Denise, Franzini, Maria, Oliveri, Paolo, Lomonaco, Tommaso, Ghimenti, Silvia, Bonini, Andrea, Vivaldi, Federico, Macera, Lisa, Balas, Laurence, Durand, Thierry, Oger, Camille, Galano, Jean-Marie, Maggi, Fabrizio, Celi, Alessandro, Paolicchi, Aldo, Di Francesco, Fabio
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; COVID-19; Endocrinology and metabolism; Human health and pathology; Humans; Inflamamtion; Inflammation; Inflammation regulation; Life Sciences; Lipid mediator class switching; Oxylipins; Retrospective Studies; SARS-CoV-2; Severity predictors; UHPLC-MS/MS
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.01.021

The key role of inflammation in COVID-19 induced many authors to study the cytokine storm, whereas the role of other inflammatory mediators such as oxylipins is still poorly understood. IMPRECOVID was a monocentric retrospective observational pilot study with COVID-19 related pneumonia patients (n = 52) admitted to Pisa University Hospital between March and April 2020. Our MS-based analytical platform permitted the simultaneous determination of sixty plasma oxylipins in a single run at ppt levels for a comprehensive characterisation of the inflammatory cascade in COVID-19 patients. The datasets containing oxylipin and cytokine plasma levels were analysed by principal component analysis (PCA), computation of Fisher’s canonical variable, and a multivariate receiver operating characteristic (ROC) curve. Differently from cytokines, the panel of oxylipins clearly differentiated samples collected in COVID-19 wards (n = 43) and Intensive Care Units (ICUs) (n = 27), as shown by the PCA and the multivariate ROC curve with a resulting AUC equal to 0.92. ICU patients showed lower (down to two orders of magnitude) plasma concentrations of anti-inflammatory and pro-resolving lipid mediators, suggesting an impaired inflammation response as part of a prolonged and unsolvable pro-inflammatory status. In conclusion, our targeted oxylipidomics platform helped shedding new light in this field. Targeting the lipid mediator class switching is extremely important for a timely picture of a patient’s ability to respond to the viral attack. A prediction model exploiting selected lipid mediators as biomarkers seems to have good chances to classify patients at risk of severe COVID-19. •Sixty oxylipins were successfully quantified in plasma of COVID-19 patients by MEPS-UHPLC-MS/MS platform.•Lipid mediators help to classify patients at risk of severe COVID-19.•Severe COVID-19 is associated with a selective deficiency of pro-resolving mediators.