Comment on "Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19".

Dear Editor,

I read with this informative review article by Cheng et al “Organ‐protective effect of angiotensin‐converting enzyme 2 (ACE2) and its effect on the prognosis of COVID‐19.” They mentioned that the protective effect of ACE2 on heart and lung. However, it is still under discussion whether the COVID‐19 patients could be beneficial from a high level of ACE2 expression. Furthermore, it is still unclear whether hypertension‐linked COVD‐19 patients should continue to take ACEI/ARBs. Here, I would like to talk about the role of ACE2 concerning endothelial cell function. Besides, I would like to mention that COVID‐19 patients might benefit from ACEI/ARBs concerning improving endothelial dysfunction in COVID‐19.

It is well studied that SARS‐CoV‐2 infects the host by binding ACE2 receptor, which is widely expressed in endothelial cells. The evidence was further shown that endothelial cells were infected by the virus leading to endothelial dysfunction in COVID‐19 patients. Therefore, improving endothelial function may open a new therapeutic avenue in COVID‐19 patients.

It is well established that Angiotensin II (ANG II) is one of the main effectors of endothelial dysfunction and is mainly regulated by the renin‐angiotensin system (RAS)

ACE2 played as a negative regulator of the RAS, which promotes the degradation of ANG II and maintains endothelium homeostasis. Several studies have shown overexpression of ACE2 could improve endothelial repair and regeneration. , In addition, virus‐induced ACE2 abscission and a decrease in the level of ACE2 contribute to developing pulmonary edema and acute respiratory distress syndrome. Taken together, above studies indicate that the approaches to increase ACE2 may provide effective therapy for improving endothelial dysfunction in COVID‐19.

Regarding whether COVID‐19 patients with hypertension should continue to take ACEI/ARBs. On the one hand, studies have shown ACEI/ARBs increase ACE2 level, which protects heart and lung functions. Furthermore, animal and human studies confirm that the beneficial effects of ACEI in reversing endothelial dysfunction. On the other hand, regarding the concerning that the high level of ACE2 expression might facilitate infection with COVID‐19, there is no direct evidence shown that ACE2 level is positively correlated with the infection risk. Several studies reported that COVID‐19 related mortality was higher in men and the elderly than women and the young, but the level of ACE2 was shown oppositely. , Moreover, Zhang et al have reported that ACEI/ARB was associated with lower mortality in COVID‐19 patients with hypertension. In conclusion, COVID‐19 patients with hypertension may benefit from ACEI/ARBs by increasing ACE2 and improving endothelial functions. Besides, other antihypertension drugs, such as amiloride, might be used to treat hypertension‐linked COVID, which has shown improved endothelial functions. ,

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.