Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19
Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19
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DOI：
10.1161/atvbaha.120.315595
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发表时间：
2021-05-05
影响因子：
8.7
通讯作者：
Susen, Sophie
中科院分区：
文献类型：
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作者：
Dupont, Annabelle;Rauch, Antoine;Susen, Sophie
目的：内皮病是否仅反映 2019 年冠状病毒病 (COVID-19) 的严重程度，还是在微血管血栓形成和器官衰竭中发挥内在作用，仍有待解答。我们评估了内皮损伤和免疫失调标志物是否与器官衰竭、血栓形成和死亡相关。方法和结果：内皮损伤标志物（VWF：Ag [血管性血友病因子抗原]、PAI-1 [纤溶酶原激活剂抑制剂-1]、syndecan-1、TFPI [组织因子途径抑制剂]和可溶性血栓调节蛋白）、补体激活（C5a 和 C5b-9）、细胞因子（IL）在 82 名 COVID-19 患者入院时，对 [白细胞介素]-6、TNF [肿瘤坏死因子]-α 和 IL-2R）和中性粒细胞胞外陷阱（游离 DNA、核小体和髓过氧化物酶-DNA）进行了测量。我们还分析了成功脱离体外膜肺氧合的危重患者中收集的血栓的组织学成分。除呼吸衰竭外，VWF:Ag、PAI-1、TFPI 和 syndecan-1 与肝损伤和多器官衰竭发展独立相关，强调了内皮病在器官衰竭中的直接作用。核小体还与肝损伤、多器官衰竭和死亡相关，发生率分别为 38%、60% 和 27%。此外，包括细胞因子、补体和中性粒细胞胞外陷阱在内的免疫反应失调与内皮损伤、呼吸衰竭和肝损伤的标志物相关。与非 COVID-19 血栓相比，从体外膜氧合回路中回收的 COVID-19 血栓含有中性粒细胞积累、VWF 和显着更高数量的中性粒细胞胞外陷阱。结论：我们提供了新的关联数据，支持内皮病和失调的免疫反应通过严重 COVID-19 患者的微血管损伤参与呼吸和肝衰竭。
Objective:Whether endotheliopathy only mirrors coronavirus disease 2019 (COVID-19) severity or plays an intrinsic role in microvascular thrombosis and organ failure remains unanswered. We assessed whether markers of endothelial damage and immune dysregulation were associated with organ failure, thrombus formation, and death.Approach and Results:Markers of endothelial damage (VWF:Ag [von Willebrand factor antigen], PAI-1 [plasminogen activator inhibitor-1], syndecan-1, TFPI [tissue factor pathway inhibitor], and soluble thrombomodulin), complement activation (C5a and C5b-9), cytokines (IL [interleukin]-6, TNF [tumor necrosis factor]-alpha, and IL-2R), and neutrophil extracellular traps (cell-free DNA, nucleosomes, and myeloperoxidase-DNA) were measured at intensive care unit admission in 82 patients with COVID-19. We also analyzed the histological composition of thrombi collected in critically ill living patients successfully weaned from extracorporeal membrane oxygenation. Beside respiratory failure, VWF:Ag, PAI-1, TFPI, and syndecan-1 were independently associated with liver injury and multiorgan failure development, underlining the direct role of endotheliopathy in organ failure. Nucleosomes were also associated with liver injury, multiorgan failure, and death which occurred in 38%, 60%, and 27% of patients, respectively. Moreover, dysregulated immune response including cytokines, complement, and neutrophil extracellular traps was associated with markers of endothelial damage, respiratory failure, and liver injury. COVID-19 thrombi retrieved from extracorporeal membrane oxygenation circuitry contained accumulation of neutrophils, VWF, and significantly higher amount of neutrophil extracellular traps when compared with non-COVID-19 thrombi.Conclusions:We provide new associative data supporting that endotheliopathy and dysregulated immune responses are involved in respiratory and liver failure through microvascular damage in patients with severe COVID-19.