干扰素雾化对新型冠状病毒肺炎的临床治疗分析

doi:10.19803/j.1672-8629.2022.07.08

摘要/Abstract

摘要： 目的评价干扰素α2b（IFNα2b）雾化吸入对新型冠状病毒肺炎（COVID-19）的治疗效果,并探讨治疗时机对核酸转阴时间的影响。方法纳入2020年1月20日至2020年5月31日,于北京地坛医院住院治疗的COVID-19患者261例,根据住院期间是否应用IFNα2b雾化吸入治疗,分为干扰素治疗组（n=218）和对照组（n=43）。通过Logistic评分最近距离法对2组患者进行基线资料匹配后,干扰素治疗组86例、对照组43例纳入本次研究。观察2组患者病情严重程度、28 d病情转归、病情改善时间、住院时间、核酸转阴时间和影像学炎症吸收时间的差异,并评价干扰素应用时机对核酸转阴的影响。结果疾病严重程度方面,使用IFNα2b雾化治疗的患者结局分型主要为轻型（17.44%）和普通型（66.28%）,而对照组中轻型（30.23%）和普通型（46.51%）患者较少,重型（9.30%）、危重型（13.95%）比例较高,差异有统计学意义（P=0.032）。2组患者28 d病情转归情况存在差异,干扰素治疗组转ICU或死亡患者比例低于对照组（P=0.011）。干扰素治疗组病情改善时间优先于对照组（P=0.030）。症状方面,病程中干扰素治疗组发热患者百分比低于对照组（P<0.001）。实验室指标方面,干扰素治疗组患者入院第14 天白细胞、中性粒细胞异常比例及第28 天 NE异常比例低于对照组（P=0.015、0.015、0.014）。入院7 d内接受干扰素治疗患者核酸转阴率显著高于7 d后用药患者（P=0.047）。结论雾化吸入IFNα2b有利于COVID-19患者临床病情改善、减轻疾病严重程度,早期应用IFNα2b有助于核酸转阴。

关键词: 新型冠状病毒肺炎, 干扰素α2b, 雾化吸入, 抗病毒药物

Abstract: Objective To evaluate the therapeutic effect of interferon α2b (IFNα2b) aerosol inhalation against COVID-19 and to explore the effect of timing of treatment on the time taken by nucleic acid to become negative. Methods 271 cases of patients with COVID-19 who had been hospitalized in Beijing Ditan Hospital between January 20, 2020 and May 31, 2020 were included. According to whether interferon aerosol inhalation was used during hospitalization, these patients were divided into the interferon treatment group (n=218) and the control group (n=43). After the baseline data of the two groups was matched by the Logistic score nearest distance method, 86 cases in the interferon treatment group and 43 cases in the control group were included in this study. The severity of the disease, 28-day outcomes, the time their conditions began to improve, the length of hospital stay, the time of nucleic acid conversion and the time of imaging inflammation absorption were compared between the two groups. The influence of timing of interferon application on the speed at which nucleic acid turned negative was assessed. Results In terms of disease severity, patients who received IFNα2b aerosol treatment were mainly of the mild type (17.44%) and common type (66.28%), compared with (30.23%) and (46.51%) for the control group in which the proportions of severe (9.30%) and critical (13.95%) patients were higher, and the difference was statistically significant (P=0.032). There was difference in the 28-day outcomes of patients between the two groups. More patients were transferred to ICUs or died in the interferon treatment group than in the control group (P=0.011). The interferon treatment group improved more significantly than the control group (P=0.030). In terms of symptoms, the incidence of fever in the interferon treatment group was lower than that of the control group (P<0.001). As for laboratory indicators, the proportion of abnormal WBC and NE on the 14^th day of admission and the proportion of abnormal NE on the 28^th day in the interferon treatment group were lower than those of the control group (P=0.015, 0.015, 0.014). The proportion of patients whose nucleic acid test results turned negative after receiving interferon treatment within 7 days of admission was significantly higher than among patients who received medication 7 days after admission (P=0.047). Conclusion Aerosol inhalation of IFNα2b can help to improve the clinical conditions of patients with COVID-19 and reduce the severity of the disease. Early use of IFNα2b can quicken the rate at which nucleic acid turns negative.

Key words: COVID-19, IFNα2b, aerosol inhalation, antiviral drugs

中图分类号:

R969

葛子若, 田地, 王爱彬, 张婷玉, 任兴翔, 钱芳, 李兴旺, 陈志海. 干扰素雾化对新型冠状病毒肺炎的临床治疗分析[J]. 中国药物警戒, 2022, 19(7): 733-739.

GE Ziruo, TIAN Di, WANG Aibin, ZHANG Tingyu, REN Xingxiang, QIAN Fang, LI Xingwang, CHEN Zhihai. Therapeutic effect of interferon atomization against COVID-19[J]. Chinese Journal of Pharmacovigilance, 2022, 19(7): 733-739.

参考文献

[1] WHO. WHO Coronavirus (COVID-19) Dashboard [DB/OL].(2021-08-18)[2021-08-18]. https://covid19.who.int.
[2] WHO. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 [DB/OL].(2015-07-24) [2021-08-18]. https://www.who.int/publications/m/item/summary-of-probable-sars-cases-with-onset-of-illness-from-1-november-2002-to-31-july-2003.
[3] WHO. WHO Director-General's opening remarks at the media briefing on COVID-19 - 27 July 2020[DB/OL].(2020-07-27)[2021-11-11]. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-27-july-2020.
[4] YU DX, CHEN Q, ZHANG LL, et al.Recombinant human interferon α-2b spray for prevention of respiratory virus infections such as SARS[J]. Chinese Journal of Experimental and Clinical Virology, 2005, 19(3): 216-219.
[5] WILDE AH, RAJ VS, OUDSHOORN D, et al.MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-a treatment[J]. Journal of General Virology, 2013, 94(8): 1749-1760.
[6] SALEKI K, YARIBASH S, BANAZADEH M, et al.Interferon therapy in patients with SARS, MERS, and COVID-19: a systematic review and meta-analysis of clinical studies[J]. European Journal of Pharmacology, 2021, 906: 174248.
[7] GAO H, ZHANG LL, WEI Q, et al Recombinant human interferon α 2b nasal spray for prevention and treatment of SARS-CoV infection in Ganges River monkeys[J]. Chinese Journal of Experimental and Clinical Virology 2005, 19(3): 207-210.
[8] MANTLO E, BUKREYEVA N, MARUYAMA J, et al.Antiviral activities of type I interferons to SARS-CoV-2 infection[J]. Antiviral Research, 2020, 179: 104811.
[9] LOKUGAMAGE K G, HAGE A, VRIES M D, et al.Type I interferon susceptibility distinguishes SARSCoV-2 from SARS-CoV[J]. J Virol, 2020, 94(23): e01410-01420.
[10] ZHOU Q, CHEN V, SHANNON C P, et al.Interferon-α2b treatment for COVID-19[J]. Frontiers in Immunology, 2020, 11: 1061.
[11] JIONG Y, XUAN L, LING T, et al.Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019[J]. British Journal of Clinical Pharmacology, 2021, 87(12): 4737-4746
[12] National Health Commission, PRC. COVID-19 diagnosis and treatment protocol (trial eighth revised edition)[J]. Chin J Clin Infect Dis, 2021,14(2): 81-88.
[13] WANG Y, ZHANG D, DU G, et al.Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial[J]. Lancet, 2020, 395(10236): 1569-1578.
[14] SCAGNOLARI C, ANTONELLI G.Antiviral activity of the interferon α family: biological and pharmacological aspects of the treatment of chronic hepatitis C[J]. Expert Opinion on Biological Therapy, 2013, 13(5): 693-711.
[15] YANG E, LI MMH.All about the rna: interferon-stimulated genes that interfere with viral RNA processes[J]. Front. Immunol, 2020, 11: 605024.
[16] SAMUEL CE.Antiviral actions of interferons[J]. Clin Microbiol Rev, 2001, 14(4): 778.
[17] MANGAN NE, FUNG KY.Type I interferons in regulation of mucosal immunity[J]. Immunology and Cell Biology, 2012, 90(5): 510-519.
[18] KONNO Y, KIMURA I, URIU K, et al.SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant[J]. Cell Reports, 2020, 32(12): 108185.
[19] CHU H, CHAN JF, WANG Y, et al.Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the Pathogenesis of COVID-19[J]. Clinical Infectious Diseases, 2020, 71(6): 1400-1409.
[20] BASTARD P, ROSEN LB, ZhANG Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19[J]. Science, 2020, 370(6515): 4585.
[21] HADJADJ J, YATIM N, BARNABEI L, et al.Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients[J]. Science, 2020, 369(6504): 718-724.
[22] ZHANG Q, BASTARD P, LIU Z, et al.Inborn errors of type I IFN immunity in patients with life-threatening. COVID-19[J]. Science, 2020, 370(6515): 422.
[23] MENG Z, WANG T, LI C, et al.The effect of recombinant human interferon alpha nasal drops to prevent COVID-19 pneumonia for medical staff in an epidemic area[J]. Curr Top Med Chem, 2021, 21(10): 920-927.
[24] ZHOU Q, CHEN V, SHANNON CP, et al.Interferon-α2b Treatment for COVID-19[J]. Frontiers in Immunology, 2020, 11: 1061.
[25] PDM A, RJMB A, VJ TA, et al.Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial - Science Direct[J]. Lancet Respir Med, 2021, 9(2): 196-206.
[26] HAO SR, YAN R, ZHANG SY, et al.Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study[J]. Journal of Zhejiang University Science B, 2020, 21(8): 628-636.
[27] FU WA, LIU YA, XIA LA, et al.A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19- ScienceDirect[J]. Eclinical Medicine, 2020, 25:100478.
[28] PAN H, PETO R, HENAO-RESTREPO AM, et al.Repurposed antiviral drugs for COVID-19 - interim WHO solidarity trial results[J]. New England Journal of Medicine, 2021, 384(6): 497-511
[29] HUNG IF, LUNG KC, TSO EY, et al.Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial[J]. Lancet (London, England), 2020, 10238(395): 1695-1704.
[30] WANG N, ZHAN Y, ZHU L, et al.Retrospective multicenter cohort study shows that early interferon therapy is associated with favorable clinical responses in COVID-19 patients[J]. Cell Host & Microbe, 2020, 28(3): 455-464.