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巴瑞替尼联合治疗:对严重 SARS-CoV-2 感染的重新定位 Janus 激酶抑制剂的叙述性综述。

Baricitinib combination therapy: a narrative review of repurposed Janus kinase inhibitor against severe SARS-CoV-2 infection.

机构信息

Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Infection. 2022 Apr;50(2):295-308. doi: 10.1007/s15010-021-01730-6. Epub 2021 Dec 13.

Abstract

PURPOSE

The Coronavirus disease 2019 (COVID-19) pandemic is one of the most devastating global problems. Regarding the lack of disease-specific treatments, repurposing drug therapy is currently considered a promising therapeutic approach in pandemic situations. Recently, the combination therapy of Janus kinase (JAK) inhibitor baricitinib has been authorized for emergency COVID-19 hospitalized patients; however, this strategy's safety, drug-drug interactions, and cellular signaling pathways remain a tremendous challenge.

METHODS

In this study, we aimed to provide a deep insight into the baricitinib combination therapies in severe COVID-19 patients through reviewing the published literature on PubMed, Scopus, and Google scholar databases. We also focused on cellular and subcellular pathways related to the synergistic effects of baricitinib plus antiviral agents, virus entry, and cytokine storm (CS) induction. The safety and effectiveness of this strategy have also been discussed in moderate to severe forms of COVID-19 infection.

RESULTS

The severity of COVID-19 is commonly associated with a dysregulated immune response and excessive release of pro-inflammatory agents, resulting in CS. It has been shown that baricitinib combined with antiviral agents could modulate the inflammatory response and provide a series of positive therapeutic outcomes in hospitalized adults and pediatric patients (age ≥ two years old).

CONCLUSION

Baricitinib plus the standard of care treatment might be a potential strategy in hospitalized patients with severe COVID-19.

摘要

目的

2019 年冠状病毒病(COVID-19)大流行是全球最具破坏性的问题之一。由于缺乏针对特定疾病的治疗方法,目前重新利用药物疗法被认为是大流行情况下有前途的治疗方法。最近,Janus 激酶(JAK)抑制剂巴瑞替尼的联合治疗已被授权用于紧急 COVID-19 住院患者;然而,这种策略的安全性、药物相互作用和细胞信号通路仍然是一个巨大的挑战。

方法

在这项研究中,我们旨在通过查阅 PubMed、Scopus 和 Google Scholar 数据库上发表的文献,深入了解巴瑞替尼联合疗法在严重 COVID-19 患者中的应用。我们还重点关注了与巴瑞替尼联合抗病毒药物、病毒进入和细胞因子风暴(CS)诱导的协同作用相关的细胞和亚细胞途径。我们还讨论了这种策略在中度至重度 COVID-19 感染中的安全性和有效性。

结果

COVID-19 的严重程度通常与失调的免疫反应和促炎物质的过度释放有关,导致 CS。已经表明,巴瑞替尼联合抗病毒药物可以调节炎症反应,并为住院成年患者和儿科患者(年龄≥两岁)提供一系列积极的治疗结果。

结论

巴瑞替尼联合标准治疗可能是严重 COVID-19 住院患者的一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aadb/8666469/ab7419d5a58e/15010_2021_1730_Fig1_HTML.jpg

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