Von Willebrand Factor and Myeloperoxidase as Laboratory Predictive Markers of In-Hospital Survival in Severe COVID-19 Patients

A. Makatsariya, J. Khizroeva, Y. Schoenfeld, M. Tretyakova, E. Slukhanchuk, A. Shkoda, L. L. Pankratyeva, Mikhail I. Petrovsky, I. Mashechkin, D. Blinov, J. Gris, V. Bitsadze
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Abstract

Background. The severe acute respiratory syndrome of the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19) highlighted the central role of immunothrombosis. Severe endothelial damage with the release of unusually large multimers of von Willebrand factor (vWF) and subsequent consumption of ADAMTS-13 is described during severe COVID-19. The activation of innate immune cells among which neutrophils contribute to the formation of extracellular neutrophil traps (NETs) and to the release of myeloperoxidase (MPO) potentially contributing to the spread of inflammation and microvascular thrombosis. Objective to evaluate the ability of vWF, ADAMTS-13 and MPO to predict in-hospital mortality in severe COVID-19 patients needing mechanical ventilation. Methods. We performed a one-center observational study of 79 severe COVID-19 patients entering intensive care unit for mechanical ventilation, examining vWF, ADAMTS-13 and MPO among other potential predictors for in-hospital death. Results. After multivariate analysis, vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were finally the single two parameters which increasing values were independently associated with non-survival; vWF:Ag (U/dL): adjusted OR 3.360, 95% CI 1.5627.228, p = 0.0019; MPO:Ag (ng/ml): adjusted OR 1.062, 95% CI 1.0241.101, p = 0.0011. From these results a simplified mortality score was derived and patients categorized as having a score value higher or lower that the median value of the score: a high score value was associated with a lower cumulative survival rate (p 0.0001), 50% of the cases being dead at day 13 post-hospital admission. Conclusions. In severe COVID-19 necessitating mechanical ventilation, increasing values of MPO activity and of vWF antigen tested at admission are associated with poor survival.
血管性血友病因子和髓过氧化物酶作为重症COVID-19患者住院生存的实验室预测指标
背景。2019年SARS-CoV-2病毒介导的冠状病毒病(COVID-19)的严重急性呼吸综合征突出了免疫血栓形成的核心作用。在严重的COVID-19期间,严重的内皮损伤伴随着异常大的血管性血液病因子(vWF)的释放和随后的ADAMTS-13的消耗。先天免疫细胞的激活,其中中性粒细胞有助于细胞外中性粒细胞陷阱(NETs)的形成和髓过氧化物酶(MPO)的释放,可能有助于炎症的扩散和微血管血栓形成。目的评价vWF、ADAMTS-13和MPO对重症COVID-19机械通气患者住院死亡率的预测能力。方法。我们对79名进入重症监护病房接受机械通气的重症COVID-19患者进行了一项单中心观察性研究,检查了vWF、ADAMTS-13和MPO等院内死亡的潜在预测因子。结果。经多因素分析,vWF抗原(vWF:Ag)和MPO抗原(MPO:Ag)最终成为单一的两个参数,其升高与非生存独立相关;vWF:Ag (U/dL):调整OR为3.360,95% CI为1.5627.228,p = 0.0019;MPO:Ag (ng/ml):调整OR 1.062, 95% CI 1.0241.101, p = 0.0011。从这些结果中得出一个简化的死亡率评分,并将患者分类为评分值高于或低于评分中位数的患者:高评分值与较低的累积生存率相关(p 0.0001), 50%的病例在入院后第13天死亡。结论。在需要机械通气的重症COVID-19患者中,入院时MPO活性和vWF抗原检测值升高与生存率低有关。
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