High levels of eicosanoids and docosanoids in the lungs of intubated COVID‐19 patients

Archambault, Anne-Sophie; Zaid, Younes; Rakotoarivelo, Volatiana; Turcotte, Caroline; Doré, Étienne; Dubuc, Isabelle; Martin, Cyril; Flamand, Olivier; Amar, Youssef; Cheikh, Amine; Fares, Hakima; Hassani, Amine El; Tijani, Youssef; Côté, Andréanne; Laviolette, Michel; Boilard, Éric; Flamand, Louis; Flamand, Nicolas

doi:10.1096/fj.202100540r

Cited by 117 publications

(135 citation statements)

References 59 publications

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“…In few cases, lipidomics studies were conducted in COVID-19 BAL samples, thus reflecting lipidomics changes in the lungs of intubated patients. The results revealed increased levels of fatty acids and inflammatory lipid mediators with both pro-inflammatory (thromboxanes, prostaglandins, leukotrienes) as well as anti-inflammatory (lipoxin A4 and the D-series resolvins) capacities [81] . In other words, the lipid mediator storm occurring in severe COVID-19 engages mechanisms operating with both pro- and anti-inflammatory lipid mediators.…”

Section: Discussionmentioning

confidence: 99%

Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: Pathologic, physiologic, and detailed molecular profiling

Bednash¹,

Kagan²,

Englert³

et al. 2022

Translational Research

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Section: Discussionmentioning

confidence: 99%

Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: Pathologic, physiologic, and detailed molecular profiling

Bednash¹,

Kagan²,

Englert³

et al. 2022

Translational Research

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“…Conti et al (2020) reported that IL-1 induces TXB2 releases in activated neutrophils and macrophages, and causes leukocyte aggregation and inflammation, which would explain the dramatic thrombi formation, platelet aggregation, and organ dysfunction in COVID-19. Moreover, results of targeted lipidomic analysis of bronchoalveolar lavages from COVID-19 patients have shown that leukotrienes, and metabolites derived from AA, EPA, and DPA were all increased ( Archambault et al, 2021 ). In the present study, the metabolic levels of DHA, resolvin D2, 5-HEPE, and 5-HETE were decreased after remdesivir treatment ( Figure 4 ), which may provide considerable mirror for understanding the mechanism of COVID-19 and antiviral drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Limited literatures have reported the metabolite changes among COVID-19 patient cohorts, such as cytosine and tryptophan–nicotinamide pathways ( Blasco et al, 2020 ), lipids ( Archambault et al, 2021 ), amino acid, and fatty acid ( Shen et al, 2020 ). However, as far as we know, no eicosanoid metabolic profiling literatures were reported pertaining to remdesivir treatment both in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry

Wang

Zhao

et al. 2021

Front. Pharmacol.

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Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

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“…ACE2 that is a negative regulator of the classical angiotensin-converting enzyme (ACE) in the renin-angiotensin system (RAS) was discovered to be dysregulated (decreased levels of ACE and increased levels of ACE2 in the lung cells) in patients presenting severe symptoms of COVID-19 ( 45 ). In addition, a significant increase of bioactive lipid levels modulating lung inflammation of severe COVID-19 patients, compared to healthy controls, has been reported ( 46 ). The Authors highlighted in COVID-19 patients, a predominance of cyclooxygenase metabolites, in particular significant levels of PGE2, and also increased levels of leukotrienes, compared to controls ( 46 ).…”

Section: Susceptibility To Covid-19 Infectionmentioning

confidence: 99%

Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19

et al. 2021

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The battle against the new coronavirus that continues to kill millions of people will be still long. Novel strategies are demanded to control infection, mitigate symptoms and treatment of COVID-19. This is even more imperative given the long sequels that the disease has on the health of the infected. The discovery that S protein includes two ankyrin binding motifs (S-ARBMs) and that the transient receptor potential vanilloid subtype 1 (TRPV-1) cation channels contain these ankyrin repeat domains (TRPs-ARDs) suggest that TRPV-1, the most studied member of the TRPV channel family, can play a role in binding SARS-CoV-2. This hypothesis is strengthened by studies showing that other respiratory viruses bind the TRPV-1 on sensory nerves and epithelial cells in the airways. Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation. Lastly, treatment with agonists that down-regulate or inactivate TRPV-1 can have a beneficial action on impaired lung functions and clearance of infection. In this review, we explore the role of the TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of COVID-19, with the aim of looking at novel strategies to control infection and mitigate symptoms, and trying to translate this knowledge into new preventive and therapeutic interventions.

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High levels of eicosanoids and docosanoids in the lungs of intubated COVID‐19 patients

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 117 publications

References 59 publications

Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: Pathologic, physiologic, and detailed molecular profiling

Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: Pathologic, physiologic, and detailed molecular profiling

Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry

Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19

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