Significant aspects of COVID-19 pandemic remain obscure. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID-19. We strongly encourage the concept that thorough considerations of receptor-ligand interactions should be kept at the heart of scientific debate on infection. In this idea, the whole renin-angiotensin system has to be evaluated. We hypothesize that factors related to ethnicity, environment, behaviors, associated illness, and medications involving this complex system are probably responsible for situations regarded as anomalous from both an epidemiological and a clinical point of view, but, taken together, such factors may explain most of the aspects of current outbreak. We decided to use the analogy of a play and speculate about the possible impact in this tragedy of 1) air pollution via the interference of nitrogen dioxide on ACE2 expression; 2) the dual role of nicotine; 3) the hypothetical involvement of ACE2 polymorphisms, the relationships of which with ethnic factors and susceptibility to cardiovascular disease seems intriguing; 4) the impact on the severity of infection of hypertension and related medications acting on the renin/angiotensin system, and, finally, 5) the possible helpful role of chloroquine, thanks to its capacity of modifying ACE2 affinity to the viral spike protein by altering glycosylation. This hypothesis paper is an urgent call for the development of research programs that aim at questioning whether the putative protagonists of this tragedy are real-life actors in COVID-19.

中文翻译：

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肾素-血管紧张素系统是COVID-19大流行的核心。

COVID-19大流行的重要方面仍然不清楚。血管紧张素转化酶2（ACE2）是肾素-血管紧张素系统的组成部分，其表达在肺泡上皮细胞中占主导地位，是SARS-CoV-2（COVID-19的致病因子）的人类细胞受体。我们强烈鼓励这样一个概念，即应充分考虑受体-配体的相互作用，将其作为感染科学辩论的核心。按照这种想法，必须评估整个肾素-血管紧张素系统。我们假设，从流行病学和临床的角度来看，与种族，环境，行为，相关疾病以及涉及此复杂系统的药物相关的因素可能是导致异常的原因，但总的来说，这些因素可以解释大多数当前爆发的方面。我们决定使用戏剧的类比，并推测在这一悲剧中可能产生的影响：1）通过二氧化氮对ACE2表达的干扰而造成的空气污染；2）尼古丁的双重作用；3）假设涉及ACE2多态性，其与种族因素和对心血管疾病的易感性之间的关系似乎很有趣；4）对高血压感染的严重程度和作用于肾素/血管紧张素系统的相关药物的影响，最后，5）氯喹的可能有用的作用，这归因于其通过改变ACE2对病毒刺突蛋白的亲和力的能力糖基化。该假设文件紧急呼吁开发研究计划，旨在质疑这一悲剧的假定主角是否是COVID-19中的真实角色。