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JAK 抑制剂和 I 型干扰素在 COVID-19 患者中产生良好临床结局的能力:系统评价和荟萃分析。

JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis.

机构信息

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, 06520, USA.

Section of Pulmonary and Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, S440, 300 Cedar Street, New Haven, CT, 06520, USA.

出版信息

BMC Infect Dis. 2021 Jan 11;21(1):47. doi: 10.1186/s12879-020-05730-z.

Abstract

BACKGROUND

The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients due to their proven efficacy against diseases with excessive cytokine release and their direct antiviral ability against viruses including coronaviruses, respectively.

METHODS

A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30th 2020 and included any study type that compared treatment outcomes of humans treated with Janus kinase-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan.

RESULTS

Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03-0.39, p< 0.001) and ICU admission (OR, 0.05; 95% CI, 0.01-0.26, p< 0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68-48.54, p< 0.00001) when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04-0.85, p< 0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00-3.59, p=0.05).

CONCLUSIONS

Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.

摘要

背景

一种高致病性新型冠状病毒(SARS-CoV-2)的传播已成为百年一遇的大流行病,目前已在全球感染了超过 6300 万人。目前急需新型疗法。由于已证明 Janus 激酶抑制剂和 I 型干扰素对细胞因子过度释放的疾病具有疗效,并且分别对包括冠状病毒在内的病毒具有直接抗病毒作用,因此它们已成为 COVID-19 患者潜在的抗病毒候选药物。

方法

三位研究人员从最初到 2020 年 7 月 30 日在 MEDLINE 和 MedRxiv 上进行了搜索,包括任何比较接受 Janus 激酶抑制剂或 I 型干扰素治疗的人类与对照组之间治疗结果的研究类型。纳入标准为必须具有明确指示风险估计值的数据,或允许进行回溯计算的数据。使用 RevMan 对结果进行综合分析。

结果

在 733 项搜索研究中,我们纳入了四项随机对照试验和十一项非随机对照试验。其中五项研究为未发表研究。与标准治疗组相比,接受 Janus 激酶抑制剂治疗的患者死亡率(OR,0.12;95%CI,0.03-0.39,p<0.001)和 ICU 入住率(OR,0.05;95%CI,0.01-0.26,p<0.001)显著降低,住院出院率(OR,22.76;95%CI,10.68-48.54,p<0.00001)显著增加。接受 I 型干扰素治疗的患者死亡率(OR,0.19;95%CI,0.04-0.85,p<0.05)显著降低,出院率(OR,1.89;95%CI,1.00-3.59,p=0.05)接近显著。

结论

Janus 激酶抑制剂治疗在死亡率、ICU 入住率和出院率方面与积极的临床结局显著相关。I 型干扰素治疗与死亡率和出院率的积极临床结局相关。虽然这些数据显示出一定的前景,但还需要进行更多设计良好的 RCT 来进一步阐明 Janus 激酶抑制剂和 I 型干扰素与 COVID-19 患者临床结局之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/979d/7798315/41db7ce8ec98/12879_2020_5730_Fig1_HTML.jpg

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