Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers.
Naama KaruAlida S D KindtLieke LamontAdriaan J van GammerenAnton A M ErmensAmy C HarmsLutzen PortengenRoel C H VermeulenWillem A DikAnton W LangerakVincent H J van der VeldenThomas HankemeierPublished in: Metabolites (2022)
COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The second publication in a series reports the results of quantitative LC-MS/MS profiling of 63 small lipids including oxylipins, free fatty acids, and endocannabinoids. Compared to samples taken from ward patients, intensive care unit (ICU) patients had 2-4-fold lower levels of arachidonic acid (AA) and its cyclooxygenase-derived prostanoids, as well as lipoxygenase derivatives, exhibiting negative correlations with inflammation markers. The same derivatives showed 2-5-fold increases in recovering ward patients, in paired comparison to early hospitalisation. In contrast, ICU patients showed elevated levels of oxylipins derived from poly-unsaturated fatty acids (PUFA) by non-enzymatic peroxidation or activity of soluble epoxide hydrolase (sEH), and these oxylipins positively correlated with markers of macrophage activation. The deficiency in AA enzymatic products and the lack of elevated intermediates of pro-resolving mediating lipids may result from the preference of alternative metabolic conversions rather than diminished stores of PUFA precursors. Supporting this, ICU patients showed 2-to-11-fold higher levels of linoleic acid (LA) and the corresponding fatty acyl glycerols of AA and LA, all strongly correlated with multiple markers of excessive immune response. Our results suggest that the altered oxylipin metabolism disrupts the expected shift from innate immune response to resolution of inflammation.
Keyphrases
- physical activity
- immune response
- end stage renal disease
- body mass index
- intensive care unit
- newly diagnosed
- ejection fraction
- chronic kidney disease
- fatty acid
- coronavirus disease
- prognostic factors
- oxidative stress
- randomized controlled trial
- healthcare
- peritoneal dialysis
- magnetic resonance
- computed tomography
- sars cov
- emergency department
- high resolution
- patient reported outcomes
- magnetic resonance imaging
- anti inflammatory
- weight gain
- patient reported
- toll like receptor
- health information