Abstract：
BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is related to immune hyperactivity, the release of inflammatory cytokines, and immunothrombosis. Among the underlying mechanisms in COVID-19 thrombosis, neutrophil extracellular traps (NETs) formation, NETosis, may have a significant role. COVID-19 thrombi obtained from extracorporeal membrane oxygenation contained an accumulation of neutrophils and in a higher amount of NETs when compared with non-COVID-19 thrombi specimens.
METHODS: During sepsis and inflammatory status, NETs released from neutrophils and histones and nucleosomes extruded into the extracellular space and take part in the host innate immunity defense, inflammation, and thrombosis. Excessive NETosis is related to clinical progression and respiratory failure in infections and sepsis. NETosis act as a scaffold for thrombus formation, and new associative data support the relation between deregulated immune responses with thrombus formation and organ failure. NETosis is reported in COVID-19 patients. In COVID-19 infection, overproduction of tissue factor (TF) by neutrophils has a role in immunothrombosis. Additionally, NETs can trap TF pathway inhibitor (TFPI) as the only endogenous protein that effectively inhibits the activity of the significant proteases- complexes, TF-FVIIa and prothrombinase.
CONCLUSIONS: Because of NETosis can induce intrinsic and extrinsic coagulation cascade activation through the production of TF, activation of FXII, and inhibition of TFPI and fibrinolysis and induce immunothrombosis, targeting NETosis may diminish thrombus formation related to NETs in COVID-19 patients.
METHODS: During sepsis and inflammatory status, NETs released from neutrophils and histones and nucleosomes extruded into the extracellular space and take part in the host innate immunity defense, inflammation, and thrombosis. Excessive NETosis is related to clinical progression and respiratory failure in infections and sepsis. NETosis act as a scaffold for thrombus formation, and new associative data support the relation between deregulated immune responses with thrombus formation and organ failure. NETosis is reported in COVID-19 patients. In COVID-19 infection, overproduction of tissue factor (TF) by neutrophils has a role in immunothrombosis. Additionally, NETs can trap TF pathway inhibitor (TFPI) as the only endogenous protein that effectively inhibits the activity of the significant proteases- complexes, TF-FVIIa and prothrombinase.
CONCLUSIONS: Because of NETosis can induce intrinsic and extrinsic coagulation cascade activation through the production of TF, activation of FXII, and inhibition of TFPI and fibrinolysis and induce immunothrombosis, targeting NETosis may diminish thrombus formation related to NETs in COVID-19 patients.
摘要：
背景：2019年冠状病毒病（COVID-19）感染与免疫亢进有关，炎症细胞因子的释放，和免疫血栓形成。在COVID-19血栓形成的潜在机制中，中性粒细胞胞外陷阱（NET）的形成，NETosis,可能有重要作用。与非COVID-19血栓标本相比，从体外膜氧合获得的COVID-19血栓包含中性粒细胞的积累和更高的NETs量。
方法：在脓毒症和炎症状态期间，从中性粒细胞和组蛋白和核小体释放的NETs挤压到细胞外空间，参与宿主的先天免疫防御，炎症,和血栓形成。过度NETosis与感染和败血症的临床进展和呼吸衰竭有关。NETosis作为血栓形成的支架，新的关联数据支持免疫反应失调与血栓形成和器官衰竭之间的关系。在COVID-19患者中报告了NETosis。在COVID-19感染中，中性粒细胞过度产生组织因子（TF）在免疫血栓形成中起作用。此外,NETs可以捕获TF途径抑制剂（TFPI）作为唯一有效抑制显著蛋白酶-复合物活性的内源性蛋白，TF-FVIIa和凝血酶原酶。
结论：由于NETosis可以通过TF的产生诱导内源性和外源性凝血级联激活，FXII的激活，抑制TFPI和纤维蛋白溶解并诱导免疫血栓形成，靶向NETosis可能会减少COVID-19患者中与NETs相关的血栓形成。
方法：在脓毒症和炎症状态期间，从中性粒细胞和组蛋白和核小体释放的NETs挤压到细胞外空间，参与宿主的先天免疫防御，炎症,和血栓形成。过度NETosis与感染和败血症的临床进展和呼吸衰竭有关。NETosis作为血栓形成的支架，新的关联数据支持免疫反应失调与血栓形成和器官衰竭之间的关系。在COVID-19患者中报告了NETosis。在COVID-19感染中，中性粒细胞过度产生组织因子（TF）在免疫血栓形成中起作用。此外,NETs可以捕获TF途径抑制剂（TFPI）作为唯一有效抑制显著蛋白酶-复合物活性的内源性蛋白，TF-FVIIa和凝血酶原酶。
结论：由于NETosis可以通过TF的产生诱导内源性和外源性凝血级联激活，FXII的激活，抑制TFPI和纤维蛋白溶解并诱导免疫血栓形成，靶向NETosis可能会减少COVID-19患者中与NETs相关的血栓形成。
