A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial

作     者：Ke Hu Mengmei Wang Yang Zhao Yunting Zhang Tao Wang Zhishui Zheng Xiaochen Li Shaolin Zeng Dong Zhao Honglin Li Ke Xu Ke Lan Ke Hu;Mengmei Wang;Yang Zhao;Yunting Zhang;Tao Wang;Zhishui Zheng;Xiaochen Li;Shaolin Zeng;Dong Zhao;Honglin Li;Ke Xu;Ke Lan

作者机构：Department of Respiratory and Critical Care MedicineRenmin Hospital of Wuhan UniversityWuhan 430060China Shanghai Key Laboratory of New Drug DesignState Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of VirologyCollege of Life SciencesWuhan UniversityWuhan 430072China Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhan 430072China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2020年第35卷第6期

页      面：725-733页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基　　金：supported by the Science and Technology Key Project on Novel Coronavirus Pneumonia,Hubei Province(project number:2020FCA002 to K.H.) the Application&Frontier Research Program of Wuhan Government(2019020701011463 to K.X.) Taikang Insurance Group Co.,Ltd Beijing Taikang Yicai Foundation Special Fund for COVID-19 Research of Wuhan University for their great supports to this work。 

主　　题：DHODH inhibitors Leflunomide Coronavirus disease 2019(COVID-19) Viral shedding time Inflammation 

摘      要：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 of5 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.