High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.
High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients.
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DOI：
10.1096/fj.202100540r
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Flamand N
中科院分区：
文献类型：
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作者：
Archambault AS;Zaid Y;Rakotoarivelo V;Turcotte C;Doré É;Dubuc I;Martin C;Flamand O;Amar Y;Cheikh A;Fares H;El Hassani A;Tijani Y;Côté A;Laviolette M;Boilard É;Flamand L;Flamand N
严重急性呼吸综合征冠状病毒 2 是导致 2019 年冠状病毒病 (COVID-19) 的原因。虽然 COVID-19 通常是良性的，但一部分患者会出现严重的多叶性肺炎，并可能进展为急性呼吸窘迫综合征。严重的 COVID-19 无法治愈，而且很少有治疗方法能够显着改善临床结果。这些选择包括地塞米松和可能的阿司匹林，它们直接/间接针对多种脂质介质的生物合成/作用。我们的目标是确定重症 COVID-19 患者是否具有调节肺部炎症的生物活性脂质增加的特征。通过串联质谱法对 25 名健康对照者和 33 名需要机械通气的 COVID-19 患者进行支气管肺泡灌洗 (BAL) 的靶向脂质组学分析。来自重症 COVID-19 患者的 BAL 的特点是脂肪酸和炎症脂质介质增加。血栓素和前列腺素占主导地位。白三烯也增加，特别是 LTB4、LTE4 和 eoxin E4。源自亚油酸、花生四烯酸、二十碳五烯酸和二十二碳六烯酸的单羟基化 15-脂氧合酶代谢物也增加。最后但重要的是，专门的促消退介质，特别是脂氧素 A4 和 D 系列消退素，也增加了，这强调了严重的 COVID-19 中发生的脂质介质风暴涉及促炎和抗炎脂质。我们的数据揭示了严重 COVID-19 患者肺部发生的脂质介质风暴。我们讨论哪些临床可用药物有助于调节我们观察到的脂质组，希望最大限度地减少促炎脂质的有害影响并增强抗炎和/或促溶解脂质介质的作用。
Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID‐19). While COVID‐19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID‐19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID‐19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID‐19 patients requiring mechanical ventilation. BALs from severe COVID‐19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4, LTE4, and eoxin E4. Monohydroxylated 15‐lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro‐resolving mediators, notably lipoxin A4 and the D‐series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID‐19 involves pro‐ and anti‐inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID‐19. 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 lipid mediators.