Journal Home Online First Current Issue Archive For Authors Journal Information 中文版

Engineering >> 2020, Volume 6, Issue 10 doi: 10.1016/j.eng.2020.03.007

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

a National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518100, China

b National Engineering Research Center for the Emergence Drugs, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

# These authors contributed equally to this work.

Received: 2020-03-07 Revised: 2020-03-11 Accepted: 2020-03-12 Available online: 2020-03-18

Next Previous

Abstract

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) have been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examined the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.

Figures

Fig. 1

Fig. 2

Fig. 3

Fig. 4

References

[ 1 ] Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323(11):1061–9. link1

[ 2 ] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395 (10223):497–506. link1

[ 3 ] Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199–207. link1

[ 4 ] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–13. link1

[ 5 ] National Health Commission of the People’s Republic of China. Daily briefing on novel coronavirus cases in China [Internet]. Beijing: National Health Commission of the People’s Republic of China; c2020 [updated 2020 Mar 12; cited 2020; c2020 Feb 25]. Available form: http://en.nhc.gov.cn/DailyBriefing. html. link1

[ 6 ] Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395(10224):565–74. link1

[ 7 ] Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71. link1

[ 8 ] Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014;105:17–21. link1

[ 9 ] Grieser C, Goldmann A, Steffen IG, Kastrup M, Fernández CM, Engert U, et al. Computed tomography findings from patients with ARDS due to Influenza A (H1N1) virus-associated pneumonia. Eur J Radiol 2012;81(2):389–94. link1

[10] Chang Y, Yu C, Chang S, Galvin JR, Liu H, Hsiao C, et al. Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: evaluation with thin-section CT. Radiology 2005;236(3):1067–75. link1

[11] Madelain V, Oestereich L, Graw F, Nguyen TH, De Lamballerie X, Mentré F, et al. Ebola virus dynamics in mice treated with favipiravir. Antiviral Res 2015;123:70–7. link1

[12] Sissoko D, Laouenan C, Folkesson E, M’Lebing AB, Beavogui AH, Baize S, et al. Experimental treatment with favipiravir for Ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med 2016;13(3):e1001967. link1

[13] Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 2013;100 (2):446–54. link1

[14] Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J, et al. Favipiravir for children with Ebola. Lancet 2015;385(9968):603–4. link1

[15] MDVI, LLC. Phase 3 efficacy and safety study of favipiravir for treatment of uncomplicated influenza in adults [Internet]. Bethesda: National Library of Medicine; [update 2015 Nov 11; cited 2020 Mar 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT02008344. link1

[16] Chafekar A, Fielding BC. MERS-CoV: understanding the latest human coronavirus threat. Viruses 2018;10(2):E93. link1

Related Research