Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.
Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.
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DOI：
10.1038/s41577-021-00536-9
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Abbate A
中科院分区：
文献类型：
--
作者：
Bonaventura A;Vecchié A;Dagna L;Martinod K;Dixon DL;Van Tassell BW;Dentali F;Montecucco F;Massberg S;Levi M;Abbate A
2019冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染引起的临床综合征。患有严重疾病的患者表现出免疫系统的过度激活，这可能会影响除肺部以外的多个器官。在这里，我们提出，SARS-CoV-2感染诱导称为免疫血栓形成的过程中，激活的中性粒细胞和单核细胞与血小板和凝血级联反应相互作用，导致在小血管和大血管血管内凝块形成。微血栓并发症可能导致急性呼吸窘迫综合征（ARDS）和其他器官功能障碍。因此，旨在减少免疫血栓形成的治疗策略可能有用。几种抗血栓和免疫调节药物已被提议作为治疗SARS-CoV-2感染患者的候选药物。对SARS-CoV-2感染发病机制及其如何导致危重疾病及其并发症的理解不断加深，这可能有助于改善风险分层，并开发靶向治疗，以减少这种疾病的急性和长期后果。在这里，作者提出，SARS-CoV-2诱导血栓前状态，肺微血管和内皮损伤中的免疫血栓形成失调，这驱动了严重COVID-19的临床表现。他们讨论了正在考虑用于治疗COVID-19患者的潜在抗血栓形成和免疫调节药物。
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease. Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19. They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.
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