Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients.

Gian Paolo Rossi,Viola Sanga,Matthias Barton

doi:10.7554/elife.57278

Gian Paolo Rossi, Viola Sanga + Show 1 more

Open Access

https://doi.org/10.7554/elife.57278

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Journal: eLife	Publication Date: Apr 6, 2020
Citations: 157	License type: CC BY 4.0

Affiliation: University of Padua, University of Zurich

Abstract

The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.

Highlights

Administration of recombinant soluble human angiotensin converting enzyme-2 (ACE-2) to capture SARS-COV-2 in the bloodstream may prevent its binding to lung cells, and enhance angiotensin converting enzyme (ACE)-2 activity in lung tissue (Figure 1, panel A), which could be beneficial for COVID-19 patients with acute respiratory distress syndrome (ARDS), possibly even at a late stage of the infection for patients in intensive care requiring assisted ventilation
A disbalance between the ACE-1-Ang II-AT1R and the ACE-1–Ang II–AT2R and the ACE-2-Ang(1-7)-AT2R and the ACE-2–Ang(1-7)–MasR pathways contributes to the pathogenesis of ARDS and acute lung failure which likely is relevant for COVID-19 patients
It seems reasonable to conclude that rebalancing the system by blunting the deleterious effects of Ang II using ACEIs and angiotensinreceptor blockers (ARBs) while enhancing the ACE-2 axis is a valuable strategy to minimize the harmful effects of SARS-CoV-2 on the lungs

Summary

Short report

Human Biology and Medicine acid sequence of the spike (S) protein of the envelope that both viruses use to infect mammalian cells. Correspondence to the Lancet Respiratory Medicine suggested that patients with cardiac diseases, as hypertension and/or diabetes treated with ‘ACE-2-increasing drugs’ would be at higher risk for severe SARS-CoV-2 infection, because treatment with ACEIs and ARBs would raise ACE-2 (Fang et al, 2020). To support their contention, the authors quoted a review article that did not report such evidence (Li et al, 2017). Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have stage 3 arterial hypertension, heart failure or who had myocardial infarction, may result in clinical instability and adverse health outcomes as pointed out recently (Vaduganathan et al, 2020)

ACE inhibitors and ARBs are beneficial in ARDS

Conclusions and perspectives

Matthias Barton Matthias Barton