Abouelkhair Mohamed A
Department of Biomedical and Diagnostic Sciences, University of Tennessee College of Veterinary Medicine, 2407 River Dr, Knoxville, TN 37996, USA.
Med Hypotheses. 2020 Nov;144:110012. doi: 10.1016/j.mehy.2020.110012. Epub 2020 Jun 19.
The most serious health issue today is the rapid outbreak of Coronavirus Disease 2019 (COVID-19). More than 6,973,427 confirmed cases were diagnosed in nearly 213 countries and territories around the world and two international conveyances, causing globally over 400,000 deaths. Epidemiology, risk factors, and clinical characteristics of COVID-19 patients have been identified, but the factors influencing the immune system against COVID-19 have not been well established. Upon infection or cell damage, high amounts of adenosine triphosphate (ATP) are released from damaged cells, which serve as mediators of inflammation through purinergic cell surface receptor signaling. As a protective mechanism to prevent excessive damage to host tissue, adenosine counteracts ATP's effects by adenosine receptor stimulation to suppress the pro-inflammatory response. Adenosine is seen as a major obstacle to the efficacy of immune therapies, and the adenosinergic axis components are critical therapeutic targets for cancer and microbial infections. Pharmacologic inhibitors or antibodies specific to adenosinergic pathway components or adenosine receptors in microbial and tumor therapy have shown efficacy in pre-clinical studies and are entering the clinical arena. In this review, we provide a novel hypothesis explaining the potential for improving the efficiency of innate and adaptive immune systems by targeting adenosinergic pathway components and adenosine A receptor signaling for the treatment of COVID-19.
当今最严重的健康问题是2019冠状病毒病（COVID-19）的迅速爆发。全球近213个国家和地区以及两艘国际运输工具中确诊病例超过6973427例，导致全球超过40万人死亡。COVID-19患者的流行病学、危险因素和临床特征已被确定，但影响免疫系统对抗COVID-19的因素尚未明确。在感染或细胞损伤时，受损细胞会释放大量三磷酸腺苷（ATP），通过嘌呤能细胞表面受体信号传导作为炎症介质。作为防止宿主组织过度损伤的一种保护机制，腺苷通过刺激腺苷受体来抵消ATP的作用，从而抑制促炎反应。腺苷被视为免疫治疗疗效的主要障碍，腺苷能轴成分是癌症和微生物感染的关键治疗靶点。在微生物和肿瘤治疗中，针对腺苷能途径成分或腺苷受体的药理抑制剂或抗体在临床前研究中已显示出疗效，并正在进入临床阶段。在本综述中，我们提出了一个新的假设，即通过针对腺苷能途径成分和腺苷A受体信号传导来提高先天性和适应性免疫系统的效率，以治疗COVID-19。
