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Review
. 2020 Jul;76(1):16-22.
doi: 10.1161/HYPERTENSIONAHA.120.15291. Epub 2020 May 5.

ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective

Andrew M South  1   2   3   4 , Tammy M Brady  5 , Joseph T Flynn  6
Affiliations
Review

ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective

Andrew M South et al. Hypertension. 2020 Jul.

Abstract

Potential but unconfirmed risk factors for coronavirus disease 2019 (COVID-19) in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, ACE (angiotensin-converting enzyme) inhibitors, and Ang II (angiotensin II) receptor blockers. Coronavirus binding to ACE2 (angiotensin-converting enzyme 2), a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus, but the reasons are unclear. This review will highlight the relationship of COVID-19 with hypertension, use of ACE inhibitors and Ang II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the ACE 2/Ang-(1-7) pathway in children and the clinical evidence for how ACE inhibitors and Ang II receptor blockers affect this important pathway. Given the importance of the ACE 2/Ang-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe COVID-19.

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Conflict of interest statement

Potential Conflicts of Interest: None.

Figures

Figure 1
Figure 1
Balance of the RAAS and Impact of Age, Disease, SARS-CoV-2, and ACE inhibitors and ARBs A: In younger and healthier individuals (e.g. children), the RAAS is in balance: blood pressure is appropriate and no disease develops. B: With advancing age and in various disease states (e.g. hypertension), there is a shift towards the ACE/Ang II pathway. C: ACEi and ARB block the ACE/Ang II pathway and shift the RAAS towards ACE2/Ang-(1–7). D: SARS-CoV-2-induced ACE2 downregulation could stimulate a shift towards the ACE/Ang II pathway to propagate acute lung injury in COVID-19. E: In patients with COVID-19, ACEi and ARB therapy could block the ACE/Ang II pathway and shift the RAAS towards the ACE2/Ang-(1–7) pathway to mitigate lung injury. Pro-inflammatory and pro-fibrotic pathway in red, anti-inflammatory and anti-fibrotic pathway in blue. Dashed lines indicate decreased pathway activity. ACE, angiotensin-converting enzyme; ACEi, ACE inhibitors; Ang, angiotensin; ARB, angiotensin II receptor blocker; AT1R, Ang II type 1 receptor; COVID-19, coronavirus disease 2019; MasR, Mas receptor; RAAS, renin-angiotensin-aldosterone system; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
See this image and copyright information in PMC

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