May 03, 2020
It has recently been suggested that the angiotensin-converting enzyme (ACE-2), a key component of the Renin-Angiotensin-Aldosterone-System (RAAS) pathway, may enhance the detrimental effects of COVID-19 infection. ACE2 was proposed to be the functional receptor to SARS-CoV-2, the virus responsible for the COVID-19 pandemic, and thus facilitating coronavirus entry into human cells (Fig. 1). A few non-randomized preclinical studies have proposed that RAAS inhibitors act by increasing ACE2 expression and may not be safe in patients with COVID-19 [1].
RAAS inhibitors, including ACE inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), are widely used for the treatment of hypertension, and their link with increased risk of developing severe, and possibly fatal, COVID-19 infection has raised serious concerns in the medical community. Some media sources and small studies called for the discontinuation of ACE-I and ARBs in suspected COVID-19 cases, suggesting another class of anti-hypertensive agents replace them.
A soon to be published report by Muthiah Vaduganathan of the Brigham & Women’s Hospital (Boston, MA) [2] summarized the current state of knowledge regarding the use of ACE-I and ARBs in COVID-19 high-risk subjects. The report concludes that “Insufficient data are available to determine whether these (animal model) observations readily translate to humans, and no studies have evaluated the effects of RAAS inhibitors in COVID-19”. It goes on to recommend that abrupt/unsupervised withdrawal of ACE-I and ARBs from high-risk patients, particularly those with heart failure or myocardial infarction, may result in clinical instability and adverse health outcomes. The recommendation is that “Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk of, being evaluated for, or with COVID-19”. The report will be published in the New England Journal of Medicine.
Based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued due to concerns regarding coronavirus infection. Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in COVID-19.
For more information:
- Fang L, Karakiulakis G, Roth M. (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respiratory Medicine 8(4):e21.
- Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. (2020) Renin-Angiotensin-Aldosterone System Inhibitors in Patients with COVID-19. New England Journal of Medicine. 2020 Mar 30. DOI: 10.1056/NEJMsr2005760.
Luciana Aparecida Campos, PhD
College of Health Sciences
Abu Dhabi University
- ‘Interaction between SARS-CoV-2 and the Renin-Angiotensin-Aldosterone System’.
Doi: 10.1056/NEJMsr2005760.
SM Post
Interested in medical treatment issues related to COVID-19? Read Dr. Luciana Aparecida Campos’s latest academic article on ‘Treatment with ACE inhibitors and angiotensin receptor blockers in the COVID-19 pandemic: Lack of sufficient evidence for abandoning their use’.
