People with hypertension, diabetes, kidney and heart disease

Two classes of drugs commonly prescribed to people with hypertension, diabetes, kidney and heart disease may increase COVID-19 infection severity.

Despite this, researchers recommend that people with those conditions continue to take their medications in consultation with their physician.

The study was conducted by researchers at the University of Waterloo, who used a unique mathematical model to predict the severity of COVID-19 in patients taking two classes of drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB). These two classes of drugs increase ACE2, a receptor attached to the membranes of cells located in the lungs, arteries, heart, kidney, and intestines, which SARS-CoV-2 uses to enter our cells.

"We focussed on hypertension and the issue of people with diseases who are already in the high-risk group taking these classes of drugs that increase the ACE2 in their body and provide more receptors for SARS-CoV-2 to get into their cells," said Anita Layton, professor of Applied Mathematics, Computer Science, Pharmacy and Biology at Waterloo. "For individuals with severe hypertension, both classes of drugs actually improve the outcome. The drug will increase the enzyme ACE2, which is good for you as it's anti-inflammatory, but it also helps the virus enter your cells, which is bad."

The researchers also found that while ACEi and ARBs may facilitate tissue recovery for individuals with severe inflammation, they may exacerbate tissue damage for people with only mild chronic inflammation or none at all as the elevated viral entry outweighs the pro-inflammatory benefits of the drug.

"If you have serious hypertension, the benefit you'll get from anti-inflammatory action will outweigh the bad that viral entry will do to you," said Layton.

In undertaking the study, Layton and her student Mehrshad Sadria, a PhD student in Waterloo's Department of Applied Mathematics, built the model that simulates the effects of ACEi and ARB medications on the abundance of ACE2 and then linked that to a model of immune response which was then infected. The researchers compared the following simulations: people with blood pressure that is normal versus high, people with different levels of infection, and people who are taking the drugs or not.

"From this study, it is clear that there is no one-size-fits-all approach in drug prescription," Sadria said. "Whether ACEi and ARBs might improve or impede tissue recovery in people with COVID-19 depends on the conditions of the patient. People should, therefore, consult their doctors before making any changes regarding their medications."

The study, Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers During the COVID-19 Pandemic: A Modeling Analysis, authored by Waterloo's Faculty of Mathematics researchers Sadria and Layton, was recently published in the journal PLOS Computational Biology.

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