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本文引用的文献

1
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.SARS-CoV-2 受体 ACE2 是人类气道上皮细胞中的一种干扰素刺激基因,可在组织中的特定细胞亚群中检测到。
Cell. 2020 May 28;181(5):1016-1035.e19. doi: 10.1016/j.cell.2020.04.035. Epub 2020 Apr 27.
2
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.干扰素 beta-1b、洛匹那韦利托那韦和利巴韦林三联治疗住院 COVID-19 患者:一项开放标签、随机、2 期试验。
Lancet. 2020 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10.
3
Weak Induction of Interferon Expression by Severe Acute Respiratory Syndrome Coronavirus 2 Supports Clinical Trials of Interferon-λ to Treat Early Coronavirus Disease 2019.严重急性呼吸综合征冠状病毒2对干扰素表达的弱诱导作用支持了干扰素λ治疗早期2019冠状病毒病的临床试验。
Clin Infect Dis. 2020 Sep 12;71(6):1410-1412. doi: 10.1093/cid/ciaa453.
4
Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Suppresses Type I and Type III Interferon Induction by Targeting RIG-I Signaling.中东呼吸综合征冠状病毒核衣壳蛋白通过靶向 RIG-I 信号抑制 I 型和 III 型干扰素的诱导。
J Virol. 2020 Jun 16;94(13). doi: 10.1128/JVI.00099-20.
5
Type 1 interferons as a potential treatment against COVID-19.1 型干扰素作为一种对抗 COVID-19 的潜在治疗方法。
Antiviral Res. 2020 Jun;178:104791. doi: 10.1016/j.antiviral.2020.104791. Epub 2020 Apr 7.
6
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.SARS-CoV-2 和 SARS-CoV 在人肺中的比较复制和免疫激活特征:一项具有 COVID-19 发病机制意义的离体研究。
Clin Infect Dis. 2020 Sep 12;71(6):1400-1409. doi: 10.1093/cid/ciaa410.
7
Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19).拯救脓毒症运动:2019 冠状病毒病(COVID-19)危重症成人管理指南。
Intensive Care Med. 2020 May;46(5):854-887. doi: 10.1007/s00134-020-06022-5. Epub 2020 Mar 28.
8
Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study.SARS-CoV-2 感染后口咽后唾液样本和血清抗体反应中的病毒载量时间特征:一项观察性队列研究。
Lancet Infect Dis. 2020 May;20(5):565-574. doi: 10.1016/S1473-3099(20)30196-1. Epub 2020 Mar 23.
9
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.洛匹那韦-利托那韦治疗成人重症 COVID-19 患者的临床试验。
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Clinical Characteristics of Coronavirus Disease 2019 in China.《中国 2019 年冠状病毒病临床特征》
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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.

DOI:10.1111/bcp.14898
PMID:33982806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8239515/
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。