A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial
A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial
复制标题
DOI：
10.1007/s12250-020-00258-7
复制
发表时间：
2020-07-21
影响因子：
5.5
通讯作者：
Lan, Ke
中科院分区：
文献类型：
--
作者：
Hu, Ke;Wang, Mengmei;Lan, Ke
我们最近报道了针对人二氢乳清酸脱氢酶（DHODH）的抑制剂具有广谱抗病毒活性，包括它们对感染细胞中SARS-CoV-2复制的抑制效力。然而，来自临床研究的有限数据证明DHODH抑制剂在2019冠状病毒病（COVID-19）患者中的应用。在本研究中，我们评估了来氟米特（一种已批准的DHODH抑制剂，广泛用作治疗自身免疫性疾病的适度免疫调节剂）在小规模患者中治疗COVID-19疾病的情况。纳入了10例实验室确诊的中度COVID-19患者，肺部有明显的混浊。其中5名患者接受来氟米特治疗，另外5名患者作为空白对照，没有安慰剂。所有患者均接受了COVID-19的标准支持治疗。接受来氟米特治疗的患者的病毒排出时间（中位数为5天）短于对照组（中位数为11天，P = 0.046）。给予来氟米特的患者也显示C反应蛋白水平显著降低，表明免疫病理炎症得到了良好控制。来氟米特治疗组患者未观察到明显的不良反应，且均比对照组患者出院快。这项关于来氟米特小规模同情使用的初步研究为进一步了解来氟米特作为一种潜在的抗COVID-19抗病毒药物提供了线索。
We recently reported that inhibitors against human dihydroorotate dehydrogenase (DHODH) have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells. However, there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019 (COVID-19) patients. In the present study, we evaluated Leflunomide, an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases, in treating COVID-19 disease with a small-scale of patients. Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included. Five of the patients were treated with Leflunomide, and another five were treated as blank controls without a placebo. All the patients accepted standard supportive treatment for COVID-19. The patients given Leflunomide had a shorter viral shedding time (median of 5 days) than the controls (median of 11 days,P = 0.046). The patients given Leflunomide also showed a significant reduction in C-reactive protein levels, indicating that immunopathological inflammation was well controlled. No obvious adverse effects were observed in Leflunomide-treated patients, and they all discharged from the hospital faster than controls. This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.