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Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers.
Karu, Naama; Kindt, Alida; Lamont, Lieke; van Gammeren, Adriaan J; Ermens, Anton A M; Harms, Amy C; Portengen, Lutzen; Vermeulen, Roel C H; Dik, Willem A; Langerak, Anton W; van der Velden, Vincent H J; Hankemeier, Thomas.
  • Karu N; Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
  • Kindt A; Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
  • Lamont L; Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
  • van Gammeren AJ; Department of Clinical Chemistry and Hematology, Amphia Hospital, 4818 CK Breda, The Netherlands.
  • Ermens AAM; Department of Clinical Chemistry and Hematology, Amphia Hospital, 4818 CK Breda, The Netherlands.
  • Harms AC; Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
  • Portengen L; Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, 3584 CK Utrecht, The Netherlands.
  • Vermeulen RCH; Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, 3584 CK Utrecht, The Netherlands.
  • Dik WA; Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • Langerak AW; Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • van der Velden VHJ; Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • Hankemeier T; Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
Metabolites ; 12(7)2022 Jul 04.
Article in English | MEDLINE | ID: covidwho-1917624
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Metabo12070619

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Metabo12070619