Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

中文翻译：

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COVID-19 死亡率与肾素-血管紧张素系统之间是否存在关联？呼吁进行流行病学调查。

2019 年冠状病毒病 (COVID-19) 导致的死亡率与心血管疾病、糖尿病和高血压密切相关。这些疾病具有与肾素-血管紧张素系统（RAS）相关的潜在病理生理学特征，这可能具有临床意义。特别是，血管紧张素转换酶 2 (ACE2) 的活性在心血管疾病中失调，严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 利用该酶来引发感染。心血管疾病和药物 RAS 抑制都会增加 ACE2 水平，这可能会增加肺和心脏内 SARS-CoV-2 的毒力。相反，相关冠状病毒的机制证据表明，SARS-CoV-2 感染可能下调 ACE2，导致血管紧张素 II 毒性过度积累，从而诱发急性呼吸窘迫综合征和暴发性心肌炎。RAS 抑制可以减轻这种影响。由于机制证据相互矛盾，我们提出了澄清 RAS 抑制在 COVID-19 死亡率中的作用所必需的关键临床研究优先事项，国际研究界可以迅速解决这一问题。