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SARS-CoV-2 proteins

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    Lipid storm within the lungs of severe COVID-19 MESHD patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites.

    Authors: Anne-Sophie Archambault; Younes Zaid; Volatiana Rakotoarivelo; Etienne Dore; Isabelle Dubuc; Cyril Martin; Youssef Amar; Amine Cheikh; Hakima Fares; Amine El Hassani; Youssef Tijani; Michel Laviolette; Eric Boilard; Louis Flamand; Nicolas Flamand

    doi:10.1101/2020.12.04.20242115 Date: 2020-12-07 Source: medRxiv

    BACKGROUNDSevere Acute Respiratory Syndrome coronavirus 2 MESHD (SARS-CoV-2) is the infectious agent responsible for Coronavirus disease 2019 MESHD ( COVID-19 MESHD). While SARS-CoV-2 infections MESHD are often benign, there are also severe COVID-19 MESHD cases, characterized by severe bilobar pneumonia MESHD that can decompensate to an acute respiratory distress syndrome MESHD, notably characterized by increased inflammation MESHD and a cytokine storm. While there is no cure against severe COVID-19 MESHD cases, some treatments significantly decrease the severity of the disease, notably aspirin and dexamethasone, which both directly or indirectly target the biosynthesis (and effects) of numerous bioactive lipids. OBJECTIVEOur working hypothesis was that severe COVID-19 MESHD cases necessitating mechanical ventilation were characterized by increased bioactive lipid levels modulating lung inflammation MESHD. We thus quantitated several lung bioactive lipids using liquid chromatography combined to tandem mass spectrometry. RESULTSWe performed an exhaustive assessment of the lipid content of bronchoalveolar lavages from 25 healthy controls and 33 COVID-19 MESHD patients necessitating mechanical ventilation. Severe COVID-19 MESHD patients were characterized by increased fatty acid levels as well as an accompanying inflammatory lipid storm. As such, most quantified bioactive lipids were heavily increased. There was a predominance of cyclooxygenase metabolites, notably TXB2 >> PGE2 [~] 12-HHTrE > PGD2 HGNC. Leukotrienes were also increased, notably LTB4, 20-COOH-LTB4, LTE4, and eoxin E4. 15-lipoxygenase metabolites derived from linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids were also increased. Finally, yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also found at important levels, underscoring that the lipid storm occurring in severe SARS-CoV-2 infections MESHD involves pro- and anti-inflammatory lipids. CONCLUSIONSOur data unmask the important lipid storm occurring in the lungs of patients afflicted with severe COVID-19 MESHD. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipids.

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MeSH Disease
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SARS-CoV-2 Proteins


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