Niculae Cristian-Mihail, Hristea Adriana, Moroti Ruxandra
Infectious Diseases Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 37 Dionisie Lupu Street, 020021 Bucharest, Romania.
National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania.
Biomedicines. 2023 Mar 16;11(3):929. doi: 10.3390/biomedicines11030929.
COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD and CD lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated "cytokine storm", platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.
新型冠状病毒肺炎（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的传染病，常与肺血栓形成事件相关，尤其是在住院患者中。严重的SARS-CoV-2感染的特征是促炎状态和相关的止血失衡。免疫病理学分析支持由白细胞，尤其是中性粒细胞、CD4和CD8淋巴细胞、纤维蛋白、红细胞和血小板组成的肺动脉血栓的炎症性质。免疫细胞、细胞因子、趋化因子和补体系统是免疫血栓形成的关键驱动因素，因为它们会诱导内皮细胞损伤并启动促炎和促凝血正反馈回路。COVID-19相关的“细胞因子风暴”诱导的中性粒细胞胞外陷阱、血小板、红细胞和凝血途径闭合了炎症-内皮病变-血栓形成轴，导致SARS-CoV-2相关的肺血栓形成事件。静脉血栓栓塞的次要作用也支持免疫血栓形成的假说，胸部CT成像数据显示外周血凝块与炎性病变相关，尽管进行了常规血栓预防，但血栓形成事件的发生率仍然很高。了解COVID-19诱导的肺血栓形成背后的复杂机制将为患有严重疾病的住院患者带来未来的联合治疗，这些治疗将针对炎症和凝血途径的交叉点。
