The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1–7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.

COVID-19大流行是由使用ACE2作为受体的严重急性呼吸系统综合症冠状病毒2引起的。提高血清/组织ACE2水平的药物包括ACE抑制剂（ACEI）和血管紧张素II受体阻滞剂（ARB），这些药物通常用于高血压，心血管疾病和/或糖尿病患者。这些合并症在COVID-19患者中可能是药物治疗引起的不良结果。ACE2的增加可能会增加COVID-19的感染，严重程度或死亡率的风险，或者由于它形成血管紧张素-（1-7）的作用而具有保护性，血管紧张素-（1-7）具有抗炎/抗氧化作用，可预防糖尿病和/或高血压引起的终末器官损害。因此，存在临床不确定性。在这里，我们回顾了涉及15类药物增加ACE2水平的研究体内以及有关这些药物在COVID-19患者中的临床安全性的现有文献。此外，在对9项研究的荟萃分析进行的临床数据重新分析中，我们显示ACEIs / ARBs的使用与全因死亡率增加的风险无关。文献表明，ACEI / ARB的使用似乎在临床上是安全的，尽管在严重的COVID-19患者中使用ACEI / ARB可能会增加急性肾损伤的风险。为了明确起见，在评估所有种类的ACE2升高药物的安全性方面需要进一步的临床和机理研究。