Background

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.

Objective

To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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补体激活和内皮扰动并行COVID-19严重性和活性

背景

动物模型和少量临床报告表明，补体系统参与了2019年冠状病毒疾病（COVID-19）的严重表现。然而，尚未阐明补体对内皮病和高凝性的贡献。

目的

为了评估COVID-19患者中补体激活，内皮损伤与疾病严重程度或活动之间的关联。

方法

在这项单中心队列研究中，入院时和30天后评估了148例不同严重程度的COVID-19患者。补体激活（SC5b-9和C5a）和内皮扰动（von Willebrand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 [PAI-1]，可溶性血栓调节蛋白[sTM]，和血浆中的可溶性内皮选择素[sE-selectin]）。

结果

患者的血浆水平较高，分别为SC5b-9和C5a（p均为0.0001）以及vWF，t-PA和PAI-1（所有p均为0.0001）。它们的SC5b-9水平与vWF（r = 0.517，p = 0.0001）和平行的疾病严重程度（重度与轻度p = 0.0001，重度与中度p = 0.026，中度与轻度p = 0.001）相关。仅在患有严重疾病的患者中，sE-选择素的水平显着增加。30天后，血浆SC5b-9，C5a和vWF水平显着降低（所有p = 0.0001），并且43％的评估患者水平正常。

结论

补体激活在COVID-19的进展过程中得到增强，而在缓解过程中被减弱，从而表明其在疾病的病理生理中的作用。补体激活与内皮损伤的生物标志物之间的关联表明补体可能会导致组织损伤，并可能成为特定疗法的目标。