Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients
Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients
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DOI：
10.1007/s10456-020-09730-0
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发表时间：
2020-05-27
期刊：
影响因子：
9.8
通讯作者：
Diehl, Jean-Luc
中科院分区：
文献类型：
--
作者：
Smadja, David M.;Guerin, Coralie L.;Diehl, Jean-Luc
背景：冠状病毒病-2019年(新冠肺炎)是一种与缺血性并发症、凝血功能紊乱和内皮炎相关的呼吸系统疾病。目的探讨新冠肺炎患者以转诊至重症监护病房和/或呼吸恶化为标准的血管内皮损伤和激活相关生物标志物。方法对入院时患者血浆内皮细胞和血管生成可溶性标志物进行分析。结果研究纳入了连续40名新冠肺炎患者，他们住进了急诊科，符合住院标准。其中一半住在常规病房，住院期间没有任何ICU转院；另20人直接转院到ICU。转到ICU的患者更有可能出现淋巴细胞减少，SpO2下降，D-二聚体、CRP和肌酐水平上升。在这些患者中，可溶性E-选择素和血管生成素-2显著升高(p值分别为0.009和0.003)。利用全血基因表达谱分析，在32名患者的独立队列中证实SELE基因表达增加(编码E-选择素蛋白的基因)。在血浆中，我们发现血管生成素-2与C反应蛋白、肌酐和D-二聚体有很强的相关性(p值分别为0.001、0.001和0.003)。ROC曲线分析显示，血管生成素-2的界值为5000 pg/mL是ICU预后的最佳预测因子(Se=80.1%，Sp=70%，PPV=72.7%，NPV=77%)，并在调整肌酐、CRP或D-二聚体后的多因素分析中得到进一步证实。结论血管生成素-2是新冠肺炎患者ICU直接入院的相关预测因子。这一结果表明血管内皮细胞激活，强化了新冠肺炎相关微血管功能障碍的假设。
Background Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. Objectives To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. Methods Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. Results Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. Conclusion Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.