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干扰素-α-2b 雾化吸入可改善新型冠状病毒病患者的临床结局。

Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.

机构信息

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd, Hangzhou City, 310003, China.

出版信息

Br J Clin Pharmacol. 2021 Dec;87(12):4737-4746. doi: 10.1111/bcp.14898. Epub 2021 May 24.

Abstract

AIMS

Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19.

METHODS

A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset.

RESULTS

The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter.

CONCLUSIONS

IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study.

摘要

目的

Ⅰ型干扰素(IFN)用于治疗新型冠状病毒肺炎(COVID-19)患者,但缺乏有力的支持证据。本研究旨在探讨 IFN-α-2b 与 COVID-19 患者临床结局的相关性。

方法

共纳入 1401 例患者,其中 852 例(60.8%)患者每日两次经雾化吸入给予 500 万单位 IFN-α-2b。主要终点是由机械通气、入住重症监护病房(ICU)和死亡组成的复合终点。进行了亚组分析以探讨 IFN-α-2b 起始时间对症状出现的影响。

结果

IFN-α-2b 组的粗终点风险概率(3.8%)低于非 IFN-α-2b 组(9.3%,P<.001)。调整混杂因素后,IFN-α-2b 治疗可降低 64%的终点事件发生率(风险比,0.36;95%置信区间 [CI],0.21-0.62)。在亚组分析中,与症状出现后 0-2 天开始接受 IFN-α-2b 治疗的患者相比,症状出现后 3-5 天开始治疗的患者终点事件的风险比为 2.2(95% CI,0.43-11.13),症状出现后 6-8 天开始治疗的患者风险比为 5.89(95% CI,0.99-35.05),此后风险比仍处于较高水平。

结论

IFN-α-2b 雾化吸入治疗可能与 COVID-19 患者临床结局的改善相关,IFN-α-2b 干预的延迟与风险事件发生概率的增加相关。需要进一步的随机临床试验来验证本研究的初步发现。

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