Complement activation and endothelial perturbation parallel COVID-19 severity and activity.
Complement activation and endothelial perturbation parallel COVID-19 severity and activity.
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DOI：
10.1016/j.jaut.2020.102560
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发表时间：
2021-01
影响因子：
12.8
通讯作者：
Peyvandi F
中科院分区：
文献类型：
--
作者：
Cugno M;Meroni PL;Gualtierotti R;Griffini S;Grovetti E;Torri A;Lonati P;Grossi C;Borghi MO;Novembrino C;Boscolo M;Uceda Renteria SC;Valenti L;Lamorte G;Manunta M;Prati D;Pesenti A;Blasi F;Costantino G;Gori A;Bandera A;Tedesco F;Peyvandi F
动物模型和少数临床报告表明，补体系统参与了2019冠状病毒病（COVID-19）严重表现的发作。然而，补体对内皮病变和高凝状态的作用尚未阐明。评估COVID-19患者的补体激活、内皮损伤与疾病严重程度或活动性之间的相关性。在这项单中心队列研究中，对148名不同严重程度的COVID-19患者在入院时和30天后进行了评估。测量血浆中的补体激活标志物（SC 5 b-9和C5 a）和内皮扰动标志物（血管性血友病因子[vWF]、组织型纤溶酶原激活物[t-PA]、纤溶酶原激活物抑制剂-1 [派-1]、可溶性血栓调节蛋白[sTM]和可溶性内皮选择素[sE-选择素]）。患者的SC 5 b-9和C5 a（两者p = 0.0001）以及vWF、t-PA和派-1（所有患者p = 0.0001）血浆水平较高。他们的SC 5 b-9水平与vWF（r = 0.517，p = 0.0001）和COPD疾病严重程度（重度vs轻度p = 0.0001，重度vs中度p = 0.026和中度vs轻度p = 0.001）相关。sE-选择素水平仅在重症患者中显著升高。30天后，血浆SC 5 b-9、C5 a和vWF水平显著降低（所有患者p = 0.0001），43%的评价患者水平正常。补体激活在COVID-19进展期间增强，在缓解期间减弱，从而表明其在疾病的病理生理学中的作用。补体激活和内皮损伤的生物标志物之间的关联表明，补体可能有助于组织损伤，并可能成为特异性治疗的靶点。补体激活产物的水平随着COVID 19的严重程度和活动而增加。补体激活与COVID 19中的内皮损伤相关。补体介导对SARSCoV 2的反应，并为靶向治疗提供了理论基础。
Animal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution to endotheliopathy and hypercoagulability has not been elucidated yet. To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients. In this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma. The patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels. Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy. Levels of complement activation products increase with COVID19 severity and activity. Complement activation is correlated with endothelium damage in COVID19. Complement mediates the response to SARSCoV2 and gives a rationale for target therapy.
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