Severe coronavirus disease-2019 (COVID-19) is frequently associated with microvascular thrombosis, especially in the lung, or macrovascular thrombosis, mainly venous thromboembolism, which significantly contributes to the disease mortality burden. COVID-19 patients also exhibit distinctive laboratory abnormalities that are compatible with a prothrombotic state. The key event underlying COVID-19-associated thrombotic complications is an excessive host inflammatory response to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection generating multiple inflammatory mediators, mainly cytokines and complement activation products. The latter, along with the virus itself, the increased levels of angiotensin II and hypoxia, drive the major cellular changes promoting thrombosis, which include: (1) aberrant expression of tissue factor by activated alveolar epithelial cells, monocytes-macrophages and neutrophils, and production of other prothrombotic factors by activated endothelial cells (ECs) and platelets; (2) reduced expression of physiological anticoagulants by dysfunctional ECs, and (3) suppression of fibrinolysis by the endothelial overproduction of plasminogen activator inhibitor-1 and, likely, by heightened thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor. Moreover, upon activation or death, neutrophils and other cells release nuclear materials that are endowed with potent prothrombotic properties. The ensuing thrombosis significantly contributes to lung injury and, in most severe COVID-19 patients, to multiple organ dysfunction. Insights into the pathogenesis of COVID-19-associated thrombosis may have implications for the development of new diagnostic and therapeutic tools.

中文翻译：

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与 SARS-CoV-2 感染相关的血栓前状态：病理生理学方面。

严重冠状病毒病 2019 (COVID-19) 经常与微血管血栓形成有关，尤其是在肺中，或大血管血栓形成，主要是静脉血栓栓塞，这显着增加了疾病死亡率负担。COVID-19 患者还表现出与血栓形成前状态相符的独特实验室异常。COVID-19 相关血栓并发症的关键事件是宿主对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的过度炎症反应，产生多种炎症介质，主要是细胞因子和补体激活产物。后者，连同病毒本身，血管紧张素 II 和缺氧水平的增加，推动了促进血栓形成的主要细胞变化，其中包括：(1) 激活的肺泡上皮细胞、单核巨噬细胞和中性粒细胞异常表达组织因子，激活的内皮细胞 (ECs) 和血小板产生其他促血栓形成因子；(2) 通过功能失调的 ECs 降低生理抗凝剂的表达，和 (3) 通过内皮细胞过度产生纤溶酶原激活剂抑制剂-1 抑制纤维蛋白溶解，并且可能通过提高凝血酶介导的凝血酶可激活的纤维蛋白溶解抑制剂的激活。此外，在激活或死亡时，中性粒细胞和其他细胞会释放具有强大促血栓形成特性的核材料。随之而来的血栓形成会显着导致肺损伤，并且在大多数严重的 COVID-19 患者中，会导致多器官功能障碍。