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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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

Title
Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers
Author
Karu, Naama 1   VIAFID ORCID Logo  ; Kindt, Alida 1   VIAFID ORCID Logo  ; Lamont, Lieke 1 ; van Gammeren, Adriaan J 2 ; Ermens, Anton A M 2 ; Harms, Amy C 1   VIAFID ORCID Logo  ; Lutzen Portengen 3 ; Vermeulen, Roel C H 3 ; Dik, Willem A 4 ; Langerak, Anton W 4   VIAFID ORCID Logo  ; Vincent H J van der Velden 4   VIAFID ORCID Logo  ; Hankemeier, Thomas 1   VIAFID ORCID Logo 

 Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands; [email protected] (A.K.); [email protected] (L.L.); [email protected] (A.C.H.) 
 Department of Clinical Chemistry and Hematology, Amphia Hospital, 4818 CK Breda, The Netherlands; [email protected] (A.J.v.G.); [email protected] (A.A.M.E.) 
 Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, 3584 CK Utrecht, The Netherlands; [email protected] (L.P.); [email protected] (R.C.H.V.) 
 Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands; [email protected] (W.A.D.); [email protected] (A.W.L.); [email protected] (V.H.J.v.d.V.) 
First page
619
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
22181989
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2694028204
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.