Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of severe COVID-19 cases, according to a hypothesis proposed by Professor James Diaz of Louisiana State University Health Sciences Center.

ACEIs and ARBs are highly recommended medications for patients with cardiovascular diseases, such as refractory hypertension, coronary artery disease, heart failure, and post-myocardial infarction status.

They are also recommended for the management of cardiovascular diseases in elderly patients, and in patients with diabetes and renal insufficiency.

“ACEIs and ARBs are highly recommended medications for patients with cardiovascular diseases including heart attacks, high blood pressure, diabetes and chronic kidney disease to name a few,” Professor Diaz said.

“Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day.”

SARS-CoV-2, a novel coronavirus which causes the COVID-19 disease, binds to angiotensin converting enzyme 2 (ACE2) receptors in the lower respiratory tracts of infected patients to gain entry into the lungs.

Research in experimental models has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors.

“Since patients treated with ACEIs and ARBs will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2 infections,” Professor Diaz said.

The hypothesis is supported by a recent descriptive analysis of 1,099 patients with laboratory-confirmed COVID-19 infections treated in China during the reporting period, December 11, 2019, to January 29, 2020.

The study reported more severe disease outcomes in patients with hypertension, coronary artery disease, diabetes and chronic renal disease.

All patients with the diagnoses noted met the recommended indications for treatment with ACEIs or ARBs.

“Two mechanisms may protect children from COVID-19 infections: cross-protective antibodies from multiple upper respiratory tract infections caused by the common cold-causing alpha coronaviruses, and fewer ACE2 receptors in their lower respiratory tracts to attract the binding S proteins of the beta coronaviruses,” Professor Diaz said.

“I recommend future case-control studies in patients with COVID-19 infections to further confirm chronic therapy with ACEIs or ARBs may raise the risk for severe outcomes.”

“Patients treated with ACEIs and ARBs for cardiovascular diseases should not stop taking their medicine, but should avoid crowds, mass events, ocean cruises, prolonged air travel, and all persons with respiratory illnesses during the current COVID-19 outbreak in order to reduce their risks of infection.”

Professor Diaz described his hypothesis in a paper published in the Journal of Travel Medicine.

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James H. Diaz et al. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. Journal of Travel Medicine, published online March 23, 2020; doi: 10.1093/jtm/taaa041