ACE Inhibitors May Exacerbate COVID-19 Symptoms

Julia Robitaille ’23, Medical Sciences, April 18 2020

Figure: A graphical depiction of the renin-angiotensinogen system which controls blood pressure.

A new paper, published recently in the Journal of Travel Medicine, provides a possible explanation for exacerbated symptoms of certain patients with COVID-19. It is widely known that patients with comorbidities are at higher risk of developing a worsened version of the pneumonia-like disease. This is partly due to a repressed immune response; however, researchers discovered that in patients with cardiovascular diseases, such as high blood pressure and diabetes, the worsened disease may be an effect of the medications these patients are taking. [1],[3]

In order to understand how these medications play a role in exacerbating symptoms, we need to understand how coronaviruses attach to their host cells. SARS beta coronaviruses bind to angiotensin converting enzyme-2 (ACE2) receptors in order to enter the cell. In humans, these are located in the lower respiratory tract. Once the virus enters, it must complete its viral replication cycle to eventually infect its host and cause severe symptoms. This process can take up to two weeks to occur. [1]

Patients with cardiovascular diseases are often prescribed angiotensin-converting enzyme inhibitors (ACEIs or ACE inhibitors), which they take on a daily basis. Researchers found that patients who are administered ACE inhibitors have higher levels of ACE2 receptors in their blood after taking the medication. Since coronaviruses bind to ACE2 receptors, these patients are at a higher risk of developing more severe symptoms. The virus has extra ACE2 receptors to bind to, increasing its ability to replicate and damage the lungs. [1]

But how do ACE inhibitors increase the amount of ACE2 receptors in the blood? ACE inhibitors control high blood pressure by preventing the formation of angiotensin II—a protein that plays a major role in raising blood pressure. Angiotensin II is naturally formed by the cleaving of the angiotensin I protein by the ACE1 enzyme. Angiotensin II then binds to ACE2 receptors, resulting in elevated blood pressure. Most ACE inhibitors interfere with the ACE1 enzyme, preventing the formation of the blood-pressure raising protein angiotensin II.[2]

This works in regulating blood pressure; however, since angiotensin I is not being converted to angiotensin II, it cannot bind to the ACE2 receptor. Production of ACE2 receptors is then upregulated in an effort to increase their usage. This leads to an excess of ACE2 in the blood. As mentioned earlier, coronaviruses are known to bind to ACE2 receptors, so patients with excess ACE2 in their blood would be at higher risk for the disease.[2]

It must be noted that most patients on ACE inhibitors have underlying conditions which would also cause exacerbated symptoms; however, the influence of blood pressure medications on COVID-19 should not be overlooked.[1]

 

Sources

[1] Diaz, J. (2020, March 23). ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19, paper suggests. Retrieved from https://www.sciencedaily.com/releases/2020/03/200323101354.htm

[2] Lowe, D. (2020, March 18). Angiotensin and the Coronavirus. Retrieved April 6, 2020, from https://blogs.sciencemag.org/pipeline/archives/2020/03/17/angiotensin-and-the-coronavirus

[3] Diaz, J. H. (2020, March 23). Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. Retrieved from https://academic.oup.com/jtm/article/doi/10.1093/jtm/taaa041/5809509

Image Source: Wikimedia Commons, David Nascari and Alan Sved / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)

https://upload.wikimedia.org/wikipedia/commons/3/33/Renin-angiotensin_system.png

 

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