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Citation: Ke Hu, Mengmei Wang, Yang Zhao, Yunting Zhang, Tao Wang, Zhishui Zheng, Xiaochen Li, Shaolin Zeng, Dong Zhao, Honglin Li, Ke Xu, Ke Lan. A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial [J].VIROLOGICA SINICA, 2020, 35(6) : 725-733.  http://dx.doi.org/10.1007/s12250-020-00258-7

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

  • Corresponding author: Ke Hu, huke-rmhospital@163.com, ORCID: 0000-0001-9862-7239
    Honglin Li, hlli@ecust.edu.cn, ORCID: 0000-0003-2270-1900
    Ke Xu, xuke03@whu.edu.cn, ORCID: 0000-0002-9969-3681
    Ke Lan, klan@whu.edu.cn, ORCID: 0000-0002-0384-8598
  • Received Date: 03 June 2020
    Accepted Date: 16 June 2020
    Published Date: 21 July 2020
    Available online: 01 December 2020
  • 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.

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

      Corresponding author: Ke Hu, huke-rmhospital@163.com
      Corresponding author: Honglin Li, hlli@ecust.edu.cn
      Corresponding author: Ke Xu, xuke03@whu.edu.cn
      Corresponding author: Ke Lan, klan@whu.edu.cn
    • 1. Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
    • 2. Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
    • 3. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    • 4. Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430072, China

    Abstract: 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.