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克拉霉素的多种作用及其作为一种重新利用的药物治疗COVID-19的临床应用建议。

Diverse effects of clarithromycin and proposal of its clinical application for treating COVID-19 as a repurposing drug.

作者信息

Takemori N, Ooi H K, Imai G, Saio M

机构信息

Department of Internal Medicine, Division of Hematology, Imai Hospital, Tanaka-cho 100, Ashikaga, Tochigi 326-0822, Japan.

Yamazaki University of Animal Health Technology, 4-7-2 Minami-osawa, Hachioji, Tokyo 192-0364, Japan.

出版信息

Trop Biomed. 2021 Sep 1;38(3):343-352. doi: 10.47665/tb.38.3.077.

Abstract

Outbreak of SARS-CoV-2 has been declared a pandemic, which is a serious threat to human health. The disease was named coronavirus disease 2019 (COVID-19). Until now, several vaccines and a few drugs have been approved for the prevention and treatment for COVID-19. Recently, the effect of some macrolides including clarithromycin (CAM) on COVID-19 has attracted attention. CAM is known to have diverse effects including immunomodulatory and immunosuppressive effects, autophagy inhibition, steroid sparing effect, reversibility of drug resistance, antineoplastic effect, antiviral effect as well as bacteriostatic/bactericidal effect. Many patients with COVID-19 died due to an overwhelming response of their own immune system characterized by the uncontrolled release of circulating inflammatory cytokines (cytokine release syndrome [CRS]). This CRS plays a major role in progressing pneumonia to acute respiratory distress syndrome (ARDS) in COVID-19 patients. It is noteworthy that CAM can suppress inflammatory cytokines responsible for CRS and also has anti-SARS-CoV-2 effect. Considering the rapidly progressive global disease burden of COVID 19, the application of CAM for treating COVID-19 needs to be urgently evaluated. Recently, an open-labeled non-randomized trial using CAM for treating COVID-19 (ACHIEVE) was initiated in Greece in May, 2020. Its results, though preprint, indicated that CAM treatment of patients with moderate COVID-19 was associated with early clinical improvement and containment of viral load. Thus, treatment with CAM as a single agent or combined with other anti-SARS CoV-2 drugs should be tried for treating COVID-19. In this article, we discussed the significance and usefulness of CAM in treating COVID-19.

摘要

严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的爆发已被宣布为大流行,这对人类健康构成严重威胁。该疾病被命名为2019冠状病毒病(COVID-19)。到目前为止,已有几种疫苗和一些药物被批准用于预防和治疗COVID-19。最近,包括克拉霉素(CAM)在内的一些大环内酯类药物对COVID-19的作用引起了关注。已知CAM具有多种作用,包括免疫调节和免疫抑制作用、自噬抑制、类固醇节省作用、耐药性逆转、抗肿瘤作用、抗病毒作用以及抑菌/杀菌作用。许多COVID-19患者死于自身免疫系统的过度反应,其特征是循环炎症细胞因子的不受控制释放(细胞因子释放综合征[CRS])。这种CRS在COVID-19患者的肺炎进展为急性呼吸窘迫综合征(ARDS)中起主要作用。值得注意的是,CAM可以抑制导致CRS的炎症细胞因子,并且还具有抗SARS-CoV-2作用。考虑到COVID-19迅速加重的全球疾病负担,迫切需要评估CAM在治疗COVID-19中的应用。最近,2020年5月在希腊启动了一项使用CAM治疗COVID-19的开放标签非随机试验(ACHIEVE)。其结果虽然是预印本,但表明CAM治疗中度COVID-19患者与早期临床改善和病毒载量控制有关。因此,应尝试将CAM作为单一药物或与其他抗SARS-CoV-2药物联合使用来治疗COVID-19。在本文中,我们讨论了CAM在治疗COVID-19中的意义和实用性。

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