To the Editor,
We thank Dr Ajay Kumar Mishra and his colleagues for their attention to our review. 1 , 2 We strongly agree with them that it is inappropriate for COVID‐19 patients to discontinue angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) without weighing up the pros and cons. 3 , 4 Whether the renin‐angiotensin‐aldosterone system (RAAS) inhibitors may affect the prognosis of COVID‐19 patients still needs more clinical trials to confirm.
Some new data revealed that different RAAS inhibitors may have different effects on ACE2 even though their mechanisms of action are similar. 3 , 5 The antihypertensive efficacy of ACEI and ARB, Ferrario et al found that blood pressure of two arms equivalently decreased after lisinopril or losartan was administrated in rats. Importantly, they also reported that the ACE2 level has a significant difference between the lisinopril group and losartan group with 4.7 and 2.8 times higher, respectively. 6 Whether RAAS inhibitors may work on ACE2 in the lungs needs further investigation.
Based on the distribution and expression of ACE2 in tissues and organs as well as the possible mechanisms that mediate the pathogenesis of COVID‐19 via the classical RAAS axis, the knowledge of RAAS inhibitors and the crucial role of ACE2 in COVID‐19 should be elucidated in the future study. Recent studies confirmed that a high level of Ang II has a good relationship with the severity of lung injury in COVID‐19 patients. 7 ACE2 is highly expressed on type II alveolar epithelial cells, the role of ACE2 in the lungs appears to be relatively minimal under normal conditions. 8 However, it could be activated to regulate and antagonize the pulmonary injury induced by Ang II during the ill conditions. Unfortunately, there was a report that SARS‐CoV‐2 may cause lung injury by downregulating ACE2. Although there is no evidence that RAAS inhibitors impact on ACE2 in the lungs, upregulation ACE2 in the lung may be a potential therapeutic approach to improve the prognosis of COVID‐19 patients.
An interesting study by Swedish scientists revealed that the dose‐dependent inhibiting effect of human recombinant soluble ACE2 (hrsACE2) on SARS‐CoV‐2 by competitively inhibiting the viral binding to the target cells. 9 Since there are few side effects, hrsACE2 may become a promising new treatment agent for COVID‐19. Furthermore, rhACE2 combined with RAAS inhibitors could be the new option to improve the outcome of COVID‐19 patients in the near future.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
AUTHOR CONTRIBUTIONS
CH wrote this response letter, including the concept of this letter, definition of intellectual content, and data acquisition; YW and G‐QW designed and reviewed the manuscript for its intellectual content.
ACKNOWLEDGMENTS
This study was supported by the National Natural Science Foundation of China (#81870417 to YW) and 13th Five‐Year National Science and Technology Major Project (#2018ZX10302206‐001‐007 to YW and #2017ZX10203202 to G‐QW).
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