Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Paris, France.
J Thromb Haemost. 2021 Jul;19(7):1823-1830. doi: 10.1111/jth.15339. Epub 2021 May 17.
Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with vascular inflammation and endothelial injury.
To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF-2) to in-hospital mortality in COVID-19 adult patients.
Consecutive ambulatory and hospitalized patients with COVID-19 infection were enrolled. VEGF-A, PlGF, and FGF-2 were measured in each patient ≤48 h following admission.
The study enrolled 237 patients with suspected COVID-19: 208 patients had a positive diagnostic for COVID-19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF-A, PlGF, and FGF-2 significantly increase with the severity of the disease (P < .001). Using a logistic regression model, we found a significant association between the increase of FGF-2 or PlGF and mortality (odds ratio [OR] 1.11, 95% confidence interval [CI; 1.07-1.16], P < .001 for FGF-2 and OR 1.07 95% CI [1.04-1.10], P < .001 for PlGF) while no association were found for VEGF-A levels. Receiver operating characteristic curve analysis was performed and we identified PlGF above 30 pg/ml as the best predictor of in-hospital mortality in COVID-19 patients. Survival analysis for PlGF confirmed its interest for in-hospital mortality prediction, by using a Kaplan-Meier survival curve (P = .001) and a Cox proportional hazard model adjusted to age, body mass index, D-dimer, and C-reactive protein (3.23 95% CI [1.29-8.11], P = .001).
Angiogenic factor PlGF is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that PlGF blocking strategies could be a new interesting therapeutic approach in COVID-19.
2019 年冠状病毒病（COVID-19）是一种与血管炎症和内皮损伤相关的呼吸道疾病。
将循环血管生成标志物血管内皮生长因子 A（VEGF-A）、胎盘生长因子（PlGF）和成纤维细胞生长因子 2（FGF-2）与 COVID-19 成年患者的住院死亡率相关联。
连续招募患有 COVID-19 感染的门诊和住院患者。在每位患者入院后≤48 小时内测量 VEGF-A、PlGF 和 FGF-2。
该研究纳入了 237 例疑似 COVID-19 患者：208 例患者对 COVID-19 的诊断呈阳性，其中 23 例为轻度门诊患者，185 例住院。VEGF-A、PlGF 和 FGF-2 水平随着疾病严重程度的增加而显著升高（P<0.001）。使用逻辑回归模型，我们发现 FGF-2 或 PlGF 的增加与死亡率之间存在显著关联（优势比[OR] 1.11，95%置信区间[CI；1.07-1.16]，P<0.001 用于 FGF-2 和 OR 1.07 95%CI [1.04-1.10]，P<0.001 用于 PlGF），而 VEGF-A 水平则没有关联。进行了接收者操作特征曲线分析，我们发现 PlGF 高于 30pg/ml 是 COVID-19 患者住院死亡率的最佳预测因子。PlGF 的生存分析证实了其对住院死亡率预测的意义，通过使用 Kaplan-Meier 生存曲线（P=0.001）和调整年龄、体重指数、D-二聚体和 C 反应蛋白的 Cox 比例风险模型（3.23 95%CI [1.29-8.11]，P=0.001）。
血管生成因子 PlGF 是 COVID-19 患者住院死亡率的一个相关预测因素。我们假设 PlGF 阻断策略不仅仅是一种生物标志物，而是 COVID-19 的一种新的有前途的治疗方法。
