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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(10): 1683-1692
DOI: 10.1055/s-0042-1749438
Cellular Haemostasis and Platelets

The Platelet Lipidome Is Altered in Patients with COVID-19 and Correlates with Platelet Reactivity

Alex R. Schuurman   *
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Valentine Léopold    *
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
2   Department of Anesthesia and Intensive Care, Hôpital Lariboisière, INSERM U942S MASCOT, Université de Paris, Paris, France
,
Liza Pereverzeva
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Osoul Chouchane
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Tom D. Y. Reijnders
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Justin de Brabander
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Renée A. Douma
3   Department of Internal Medicine, Flevo Hospital, Almere, The Netherlands
,
Michel van Weeghel
4   Departments of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
6   Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands
,
Eric Wever
4   Departments of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
6   Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands
5   Department of Epidemiology & Data Science, Bioinformatics Laboratory, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
,
Bauke V. Schomaker
4   Departments of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
6   Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands
,
Frédéric M. Vaz
4   Departments of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
6   Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands
7   Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
,
Willem Joost Wiersinga
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
8   Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Cornelis van't Veer
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
,
Tom van der Poll
1   Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
8   Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations Funding This work was supported by the Netherlands Organization for Health Research and Development (ZonMW grant #50-53000-98-139 to T.v.d.P.). V.L. is supported by Assistance Publique des Hôpitaux de Paris, Fondation Bettencourt-Schueller; L.P. is supported by JPI-AMR/ZonMW # 547001008; O.C. is supported by Landsteiner Foundation (LSBR # 1901). T.D.Y.R. is supported by NACTAR (# 16447) financed by the Dutch Research Council (NWO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Abstract

Background Activated platelets have been implicated in the proinflammatory and prothrombotic phenotype of coronavirus disease 2019 (COVID-19). While it is increasingly recognized that lipids have important structural and signaling roles in platelets, the lipidomic landscape of platelets during infection has remained unexplored.

Objective To investigate the platelet lipidome of patients hospitalized for COVID-19.

Methods We performed untargeted lipidomics in platelets of 25 patients hospitalized for COVID-19 and 23 noninfectious controls with similar age and sex characteristics, and with comparable comorbidities.

Results Twenty-five percent of the 1,650 annotated lipids were significantly different between the groups. The significantly altered part of the platelet lipidome mostly comprised lipids that were less abundant in patients with COVID-19 (20.4% down, 4.6% up, 75% unchanged). Platelets from COVID-19 patients showed decreased levels of membrane plasmalogens, and a distinct decrease of long-chain, unsaturated triacylglycerols. Conversely, platelets from patients with COVID-19 displayed class-wide higher abundances of bis(monoacylglycero)phosphate and its biosynthetic precursor lysophosphatidylglycerol. Levels of these classes positively correlated with ex vivo platelet reactivity—as measured by P-selectin expression after PAR1 activation—irrespective of disease state.

Conclusion Taken together, this investigation provides the first exploration of the profound impact of infection on the human platelet lipidome, and reveals associations between the lipid composition of platelets and their reactivity. These results warrant further lipidomic research in other infections and disease states involving platelet pathophysiology.

Keywords

platelets - platelet activation - lipidomics - COVID-19 - plasmalogens

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author.


* A.R.S. and V.L. are co-first authors.


Supplementary Material



Publication History

Received: 09 December 2021

Accepted: 30 March 2022

Article published online:
18 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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