Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, United States.
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, United States.
Front Immunol. 2021 Feb 12;12:574425. doi: 10.3389/fimmu.2021.574425. eCollection 2021.
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.
新型冠状病毒肺炎（COVID-19）疫情的迅速蔓延促使人们加速寻找有效的治疗方法。疾病进程可根据病毒载量、肺部病理和免疫反应阶段进行定义。免疫相关因素包括炎症细胞浸润和细胞因子风暴与重症和死亡相关。目前正在研究许多针对 COVID-19 的免疫调节疗法，初步结果支持针对免疫反应的前提。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与疾病进程的时间关系。阿奇霉素是一种免疫调节剂，已被证明对 COVID-19 患者具有抗病毒作用和潜在益处。阿奇霉素具有多种免疫调节作用，可能在疾病晚期提供疗效，包括抑制促炎细胞因子的产生、抑制中性粒细胞浸润、诱导巨噬细胞的调节功能以及自噬的改变。在此，我们回顾了这些机制的已发表证据，以及阿奇霉素作为免疫调节治疗的当前临床应用。然后，我们讨论了阿奇霉素对 COVID-19 免疫反应的潜在影响，并警告在这些患者中避免免疫抑制和脱靶效应，包括心脏毒性。虽然阿奇霉素有可能发挥疗效，但它对 COVID-19 免疫反应的影响需要进一步描述，以便更好地定义其在个体化治疗中的作用。
