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

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

doi:10.1007/s12250-020-00258-7

December 2020

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

Ke Hu ^{1,
,,} ,
Mengmei Wang ^1, ,
Yang Zhao ^1, ,
Yunting Zhang ¹ ,
Tao Wang ¹ ,
Zhishui Zheng ¹ ,
Xiaochen Li ¹ ,
Shaolin Zeng ¹ ,
Dong Zhao ¹ ,
Honglin Li ^{2
,,} ,
Ke Xu ^{3
,,} ,
Ke Lan ^{3,4
,,}

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

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
Ke Hu, Mengmei Wang and Yang Zhao contributed equally to this work.
Received Date: 03 June 2020
Accepted Date: 16 June 2020
Published Date: 21 July 2020
Available online: 01 December 2020

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.
- DHODH inhibitors
- , Leflunomide
- , Coronavirus disease 2019 (COVID-19)
- , Viral shedding time
- , Inflammation

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