Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System? A Call for Epidemiologic Investigations
Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System? A Call for Epidemiologic Investigations
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DOI：
10.1093/cid/ciaa329
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发表时间：
2020-08-01
影响因子：
11.8
通讯作者：
Mohareb, Annie M.
中科院分区：
文献类型：
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作者：
Hanff, Thomas C.;Harhay, Michael O.;Mohareb, Annie M.
2019冠状病毒病（COVID-19）的死亡率与心血管疾病、糖尿病和高血压密切相关。这些疾病共享潜在的病理生理学相关的肾素-血管紧张素系统（RAS），可能是临床上有见地。特别是，血管紧张素转换酶2（ACE 2）的活性在心血管疾病中失调，并且这种酶被严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）用来启动感染。心血管疾病和药理学RAS抑制都增加ACE 2水平，这可能增加肺和心脏内SARS-CoV-2的毒力。相反，来自相关冠状病毒的机制证据表明，SARS-CoV-2感染可能下调ACE 2，导致血管紧张素II的毒性过度积累，诱导急性呼吸窘迫综合征和暴发性心肌炎。RAS抑制可减轻这种作用。鉴于相互矛盾的机制证据，我们提出了关键的临床研究优先事项，以澄清RAS抑制在COVID-19死亡率中的作用，国际研究界可以迅速解决这一问题。
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.