Background

Microthrombosis is a hallmark of COVID-19. We previously described von willebrand factor (VWF) and their high molecular weight multimers (HMWMs) as potential trigger of microthrombosis.

Objectives

Investigate VWF activity with collagen-binding assay and ADAMTS13 in COVID-19.

Methods and results

Our study enrolled 77 hospitalized COVID-19 patients including 37 suffering from a non-critical form and 40 with critical form. Plasma levels of VWF collagen-binding ability (VWF:CB) and ADAMTS13 activity (ADAMTS13:Act) were measured in the first 48 hours following admission. VWF:CB was increased in critical (631% IQR [460–704]) patients compared to non-critical patients (259% [235–330], p < 0.005). VWF:CB was significantly associated (r = 0.564, p < 0.001) with HMWMs. Moreover, median ADAMTS13:Act was lower in critical (64.8 IU/dL IQR 50.0–77.7) than non-critical patients (85.0 IU/dL IQR 75.8–94.7, p < 0.001), even if no patients displayed majors deficits. VWF:Ag-to-ADAMTS13:Act ratio was highly associated with VWF:CB (r = 0.916, p < 0.001). Moreover, VWF:CB level was highly predictive of COVID-19 in-hospital mortality as shown by the ROC curve analysis (AUC = 0.92, p < 0.0001) in which we identified a VWF:CB cut-off of 446% as providing the best predictor sensitivity–specificity balance. We confirmed this cut-off thanks to a Kaplan–Meier estimator analysis (log-rank p < 0.001) and a Cox-proportional Hazard model (HR = 49.1, 95% CI 1.81–1328.2, p = 0.021) adjusted on, BMI, C-reactive protein, and D-dimer levels.

Conclusion

VWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity.

中文翻译：

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Von Willebrand 因子胶原结合能力可预测 COVID-19 患者的住院死亡率：来自 VWF/ADAMTS13 比例失衡的见解

背景

微血栓形成是 COVID-19 的标志。我们之前将血管性血友病因子 (VWF) 及其高分子量多聚体 (HMWMs) 描述为微血栓形成的潜在触发因素。

目标

用胶原蛋白结合试验和 ADAMTS13 在 COVID-19 中研究 VWF 活性。

方法和结果

我们的研究招募了 77 名住院的 COVID-19 患者，其中 37 名患有非危重症，40 名患有危重症。在入院后的前 48 小时内测量 VWF 胶原蛋白结合能力 (VWF:CB) 和 ADAMTS13 活性 (ADAMTS13:Act) 的血浆水平。与非危重患者相比，危重患者（631% IQR [460–704]）的 VWF:CB 增加（259% [235–330]，p  < 0.005）。VWF:CB 与 HMWM 显着相关 ( r  = 0.564, p  < 0.001)。 此外，即使没有患者表现出严重缺陷，危重患者（64.8 IU/dL IQR 50.0-77.7）的 ADAMTS13:Act 中位数也低于非危重患者（85.0 IU/dL IQR 75.8-94.7，p < 0.001）。VWF:Ag 与 ADAMTS13:Act 比率与 VWF:CB 高度相关（r  = 0.916，p  < 0.001）。此外，如 ROC 曲线分析 (AUC = 0.92, p < 0.0001)所示，VWF:CB 水平对 COVID-19 住院死亡率具有高度预测性，在该分析 中我们确定了 446% 的 VWF:CB 截止值作为提供最佳预测指标敏感性-特异性平衡。由于 Kaplan-Meier 估计量分析（对数秩p  < 0.001）和 Cox 比例危险模型（HR = 49.1, 95% CI 1.81–1328.2, p  = 0.021）调整，我们确认了这个截止值，BMI， C-反应蛋白和 D-二聚体水平。

结论

VWF:CB 水平可以总结 ADAMTS13 溢出后 VWF 增加的水平和高反应性，因此，它是一种有价值且易于执行的微血栓形成和 COVID-19 严重程度的临床生物标志物。