法维拉韦治疗新型冠状病毒肺炎重症发生率的临床观察

doi:10.19803/j.1672-8629.2021.10.01

摘要/Abstract

摘要： 目的通过匹配对照队列临床研究分析法维拉韦（favipiravir, FPV）治疗新型冠状病毒肺炎（coronavirus di-sease 2019,COVID-19）的疗效。方法根据年龄、性别、基础病以及入院时血常规、C反应蛋白（CRP）及血清淀粉样蛋白A（SAA）水平进行倾向性得分,并按照1∶1（治疗组∶常规治疗组）进行匹配。治疗组给药方案为口服FPV（第1天：给药2次,单次1 600 mg;第2~10天：每日2次,单次600 mg）,对照组为常规治疗。FPV治疗组的147例患者和对照组的147例患者在入组时,两组之间患者的所有基线特征均具有可比性。回顾性分析比较两组患者在住院时间、病毒清除、胸部CT等方面的变化。结果治疗组住院时间中位数为29（24,39）d、对照组为32（22,44）d,无统计学差异（P=0.575）。治疗组新冠病毒核酸转阴时间中位数为25（18,33）d、对照组为25（13,40）d,无统计学差异（P=0.982）。治疗组中,9例患者发展为重型或危重型,而对照组中32例患者发展为重型或危重型,治疗组重症发生率明显低于对照组,有统计学差异（P=0.000）。重型或危重型患者中,治疗组住院时间及病毒核酸转阴时间均优于对照组,但两组无统计学差异（P=0.116、0.133）。重型或危重型患者中,治疗组胸部CT缓解时间为（9.38±4.94）d、对照组为（13.44±4.67）d,明显短于对照组,两组间有统计学差异（P=0.033）。结论 FPV治疗减少了新型冠状病毒肺炎患者重症发生率,有利于重症患者肺部炎症的吸收,初步为新型冠状病毒肺炎患者的抗病毒治疗提供了有价值的信息。

关键词: 法维拉韦, 新型冠状病毒, 新型冠状病毒肺炎, 临床观察, 倾向性评分

Abstract: Objective To analyze the efficacy of favipiravir in the treatment of COVID-19 via a matched cohort study. Methods According to age, gender, blood routine results, C-reactive protein and SAA levels at admission, propensity scores were calculated and matched at the ratio of 1∶1 (treatment group vs control group). The treatment group was given oral FPV (day 1: twice, a single dose of 1600 mg, day 2: twice, a single dose of 1 600 mg, and days 2~5: twice a day, a single dose of 600 mg). The control group received routine treatment. There were 147 patients in either group. The duration of hospital stay, rate of virus clearance and chest CT were compared between the two groups. Results The median time of hospital stay was 29 (24,39) days in the treatment group and 32 (22,44) days in the control group, so there was no significant difference between the two groups (P=0.575). The median time taken by viral clearance was 25 (18,33) days in the treatment group and 25 (13,40) days in the control group, so there was no significant difference between the two groups (P=0.982). In the treatment group, 9 patients became severe or critically severe, compared with 32 in the control group. The incidence of severe cases in the treatment group was significantly lower than in the control group (P=0.000). For severe patients, the mean time of hospital stay and viral shedding in the treatment group was shorter than in the control group, but there was no significant difference between the two groups (P=0.116, 0.133). The remission time of CT in the treatment group was (9.38±4.94) days and (13.44±4.67) days in the control group, which were significantly shorter than in the control group (P=0.033). Conclusion In this study, treatment of COVID-19 with FPV can reduce the incidence of critically ill cases, and FPV can contribute to the remission of CT in severe or critically ill patients.

Key words: favipiravir, SARS-CoV-2, COVID-19, clinical observation, propensity score

中图分类号:

R978.7

田地, 葛子若, 钱芳, 张婷玉, 宋美华, 韩冰, 王爱彬, 马瑞泽, 陈志海, 徐艳利. 法维拉韦治疗新型冠状病毒肺炎重症发生率的临床观察[J]. 中国药物警戒, 2021, 18(10): 901-904.

TIAN Di, GE Ziruo, QIAN Fang, ZHANG Tingyu, SONG Meihua, HAN Bing, WANG Aibin, MA Ruize, CHEN Zhihai, XU Yanli. Incidence of Severe Cases of COVID-19 Treated with Favipiravir[J]. Chinese Journal of Pharmacovigilance, 2021, 18(10): 901-904.

参考文献

[1] National Health Commission of the People's Republic of China. Diagnosis and treatment plan for COVID-19(trial version 8 revision)[J]. Chinese Journal of Clinical Infectious Diseases(中华临床感染病杂志), 2021, 14(2): 81-88.
[2] Shiraki K, Daikoku T. Favipiravir an anti-influenza drug against life-threatening RNA virus infections[J/OL]. Pharmacol Ther, (2020-02-22)[2021-04-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102570/.
[3] Furuta Y, Komeno T, Nakamura T.Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2017, 93(7): 449-463.
[4] Wang XK, Sun N, Chen ZH.Progress in researches for favipiravir in anti-vital treatments[J]. Chinese Journal of New Drugs(中国新药杂志), 2019, 28(15): 1824-1827.
[5] Wang M, Cao R, Zhang L, et al.Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro[J]. Cell Re, 2020, 30(3): 269-271.
[6] Kocayiğit H, Özmen Süner K, Tomak Y, et al.Observational study of the effects of Favipiravir vs Lopinavir/Ritonavir on clinical outcomes in critically ill patients with COVID-19[J]. J Clin Pharm Ther, 2021, 46(2): 454-459.
[7] Cai Q, Yang M, Liu D, et al.Experimental treatment with favipiravir for COVID-19: an open-label control study[J]. Engineering (Beijing), 2020, 6(10): 1192-1198.
[8] Fujii S, Ibe Y, Ishigo T, et al.Early favipiravir treatment was associated with early defervescence in non-severe COVID-19 patients[J]. J Infect Chemother, 2021, 27(7): 1051-1057.
[9] Yamada Koichi. Anti-influenza drug avigan tablet meets primary endpoint in phaseⅢclinical trial in Japan for COVID-19 patients[N/OL]. Fujifilm, (2020-09-23)[2021-04-01]. https://www.fujifilm.com/jp/en/news/hq/5451.
[10] Ivashchenko AA, Dmitriev KA, Vostokova NV, et al.Avifavir for treatment of patients with moderate coronavirus disease 2019 (COVID-19): interim results of a phase ii/iii multicenter randomized clinical trial[J]. Clin Infect Dis, 2021, 73(3): 531-534.
[11] Fu D, Cao R, Zhao L, et al.Oral favipiravir for patients with delayed SARS-CoV-2 viral RNA clearance: a case series[J]. Crit Care, 2020, 24(1): 578.
[12] Chen PJ, Chao CM, Lai CC.Clinical efficacy and safety of favipiravir in the treatment of COVID-19 patients[J]. J Infect, 2021, 82(5): 186-230.
[13] Ghasemnejad-Berenji M, Pashapour S.Favipiravir and COVID-19: a simplified summary[J]. Drug Res (Stuttg), 2021, 71(3): 166-170.
[14] Zhao H, Zhang C, Zhu Q, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial [J/OL]. Int Immunopharmacol, (2021-04-21)[2021-04-22]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059985/.
[15] Doi Y, Hibino M, Hase R, et al.A prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19[J]. Antimicrob Agents Chemother, 2020, 64(12): e01897-20.
[16] Udwadia ZF, Singh P, Barkate H, et al.Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial[J]. Int J Infect Dis, 2021, 103: 62-71.
[17] Khamis F, Al Naabi H, Al Lawati A, et al.Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia [J/OL]. Int J Infect Dis, 2021, 102: 538-543.
[18] Solaymani-Dodaran M, Ghanei M, Bagheri M, et al. Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia[J/OL]. Int Immunopharmacol, (2021-03-11)[2021-04-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951885/.
[19] Chen PJ, Chao CM, Lai CC.Clinical efficacy and safety of favipiravir in the treatment of COVID-19 patients[J]. J Infect, 2021, 82(5): 186-230.
[20] Huang W, Berube J, McNamara M, et al. Lymphocyte subset counts in COVID-19 patients: a meta-analysis[J]. Cytometry A, 2020, 97(8): 772-776.
[21] Cui SP, Zhao Z, Ge ZR, et al.Analysis of early warning indexes and immune mechanism of re-positive among coronvirus disease 2019 patients[J]. International Journal of Virology, 2021, 28(1): 1-5.
[22] He J, Tao H, Yan Y, et al.Molecular mechanism of evolution and human infection with SARS-CoV-2[J]. Viruses, 2020, 12(4): 428.
[23] Ison MG, Scheetz MH. Understanding the pharmacokinetics of Favipiravir: Implications for treatment of influenza and COVID-19[J/OL]. EBioMedicine, (2021-01-06)[2021-04-01].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785424/.