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Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

Authors :
Naama Karu
Alida Kindt
Lieke Lamont
Adriaan J. van Gammeren
Anton A. M. Ermens
Amy C. Harms
Lutzen Portengen
Roel C. H. Vermeulen
Willem A. Dik
Anton W. Langerak
Vincent H. J. van der Velden
Thomas Hankemeier
Source :
Metabolites, Vol 12, Iss 7, p 619 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
22181989
Volume :
12
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.f3899c858ec42b89ad974ac82755f37
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo12070619