Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.
Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.
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DOI：
10.3389/fimmu.2021.574425
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发表时间：
2021
影响因子：
7.3
通讯作者：
Feola DJ
中科院分区：
文献类型：
--
作者：
Venditto VJ;Haydar D;Abdel-Latif A;Gensel JC;Anstead MI;Pitts MG;Creameans J;Kopper TJ;Peng C;Feola DJ
COVID-19大流行的迅速发展促使人们加快寻求有效的治疗方法。疾病进程的阶段已通过病毒负荷、肺部病理学和免疫应答阶段的进展来定义。包括炎性细胞浸润和细胞因子风暴在内的免疫因素与严重疾病和死亡相关。目前正在研究许多针对COVID-19的免疫调节疗法，初步结果支持靶向免疫反应的前提。然而，由于抑制免疫机制也可能影响感染早期病毒的清除，因此治疗成功可能取决于病程的时机。阿奇霉素是一种免疫调节药物，已被证明对COVID-19患者具有抗病毒作用和潜在获益。阿奇霉素具有多种免疫调节作用，可在疾病晚期提供疗效，包括抑制促炎细胞因子产生、抑制中性粒细胞流入、诱导巨噬细胞的调节功能和改变自噬。在这里，我们回顾了这些机制的证据，沿着阿奇霉素作为免疫调节治疗的临床应用。然后，我们讨论了阿奇霉素对COVID-19免疫反应的潜在影响，以及对这些患者的免疫抑制和脱靶效应（包括心脏毒性）的警告。虽然阿奇霉素有可能发挥疗效，但其对COVID-19免疫反应的影响需要额外的表征，以便更好地确定其在个体化治疗中的作用。
The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on timing with respect to the disease course. Azithromycin is an immunomodulatory drug that has been shown to have antiviral effects and potential benefit in patients with COVID-19. Multiple immunomodulatory effects have been defined for azithromycin which could provide efficacy during the late stages of the disease, including inhibition of pro-inflammatory cytokine production, inhibition of neutrophil influx, induction of regulatory functions of macrophages, and alterations in autophagy. Here we review the published evidence of these mechanisms along with the current clinical use of azithromycin as an immunomodulatory therapeutic. We then discuss the potential impact of azithromycin on the immune response to COVID-19, as well as caution against immunosuppressive and off-target effects including cardiotoxicity in these patients. While azithromycin has the potential to contribute efficacy, its impact on the COVID-19 immune response requires additional characterization so as to better define its role in individualized therapy.