ACE inhibitors and Angiotensin Receptor Blockers May Increase Mortality Rate In Elderly COVID-19 Patients

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Doctor holding oxygen ambu bag over patient given oxygen to patient by intubation tube in ICU/Emergency room
doctor holding oxygen ambu bag over patient given oxygen to patient by intubation tube in ICU/Emergency room

While Previous reports of which medications may influence COVID-19 symptoms and outcomes of patients have been reported on a case-by-case basis, a recent study of more than 1,000 COVID-19 positive patients from China suggests that ACE inhibitors and angiotensin receptor blockers may actually increase the risk of severe COVID-19 complications.

In response to this, James Diaz, M.D., professor and head of Environmental Health Sciences at Louisiana State University has proposed a possible explanation for the severe lung complications seen in a percentage of patients diagnosed with COVID-19. The manuscript was published by Oxford University Press online in the Journal of Travel Medicine, available here.

The SARS beta coronaviruses are well known for two types: SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, and the new SARS-CoV-2, which causes COVID-19. COVID-19 is a unique virus in its potential to infect large numbers of people, as well as its high mortality rate in patients with compromised immune systems.  COVID-19 has a mechanism of action by which it binds to angiotensin converting enzyme 2 (ACE2) receptors in the lower respiratory tracts of infected patients, in an attempt to gain entry into the lungs.

Many patients are asymptomatic or recover after a few days of illness, but viral pneumonia and potentially fatal respiratory failure may result in susceptible persons after 10-14 days. Susceptible persons are individuals with pre-existing conditions, particularly cardiovascular issues, diabetes, and breathing difficulties.

“Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (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,” noted Diaz. “Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day.”

While these medications are intended to treat more idiopathic disease by changing which proteins are expressed on the cellular surface, this could indirectly assist the virus in gaining entry into the cell and thus body. This change of cell surface protein expression is particularly problematic in cells in the respiratory system, tissue that is vulnerable to targeting and attack by the COVID-19 virus. These medication-induced tissue changes could also increase the susceptibility of the entire respiratory system, making  treatment more difficult.

Experimental research has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors, supporting this hypothesis.

“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,” explained Diaz.

Diaz believes this 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. This study reported more severe disease outcomes in patients with hypertension, coronary artery disease, diabetes and chronic renal disease. All patients with the diagnoses noted were also being treated with ACEIs or ARBs, highly suggestive of correlation, if not causation.  A large proportion of elderly patients were noted to be taking these medication types to treat these particular comorbidities, which may be what is putting them at even greater risk.

Diaz further noted that that these two mechanisms may protect children from COVID-19 infections: cross-protective antibodies from multiple upper respiratory tract infections caused by the common cold (caused by alpha coronaviruses), and fewer ACE2 receptors in the lower respiratory tract of children. Having fewer receptors to attract the binding S proteins of the beta coronaviruses may offer some protection.

He recommends 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.

In the meantime he cautions, “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.”

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