One of the things noted during the coronavirus outbreak in China and elsewhere is that there is a high propensity of severe infections and death for people with preexisting health conditions. Statistics show people with 2-3 preexisting health conditions have a much higher rate of severe illness and death. The health conditions noted have included diabetes, hypertension, heart disease and obesity.  

A letter published in The Lancet, brought this idea to a head and prompted questions from some of my patients so I would like to run through this for you. The authors proposed that people taking ACE inhibitors (examples are lisinopril, enalapril, benazepril) or angiotensin receptor blockers, also known as ARBs (losartan, olmesartan, telmisartan, valsartan, candesartan) could be at higher risk of infection. This was proposed to be due to an increase in the enzyme ARB2 which is thought to be the enzyme the virus attaches to when it enters the body. Cells with high levels of ARB2 line our airways and COVID-19 tends to be a respiratory virus. So it would seem that higher levels of ARB2 would increase risk of infection and that perhaps consideration should be given to having people stop these medications. This was proposed in a letter to the editor in the medical journal The Lancet. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?  

A third theory has come up. Could these medications actually be protective or therapeutic in more severe cases? Please bear with me as I cover some human physiology. Angiotensin-converting enzyme (ACE) and its close homologue ACE2, while both belonging to the ACE family of enzymes, serve two opposing physiological functions. ACE activates a receptor to constrict blood vessels, thereby elevating blood pressure. This is why ACE inhibitors are useful in the treatment of high blood pressure.

 

It has been demonstrated that the binding of the coronavirus spike protein to ACE2, its cellular binding site, leads to ACE2 downregulation (less ARB2), which in turn results in excessive production of angiotensin by the related enzyme ACE, while less ACE2 is around to convert it to the vasodilator enzyme. This in turn contributes to lung injury, as more ACE results in increased pulmonary vascular permeability and increased lung pathology and eventual acute respiratory distress syndrome (ARDS). ARDS is the lung injury resulting in the need for mechanical ventilation seen in COVID-19 patients.

So we see that higher ACE2 levels seen in people taking ARB or ACE inhibitor medications may protect them against acute lung injury rather than putting them at higher risk to develop ARDS.

The tentative suggestion to apply ARB/ACE inhibitors as COVID-19 therapeutics for treating patients prior to the development of acute respiratory syndrome remains unproven until tried. However, at this point we can already start to review records on people who are sickened by the virus and start to see if there seem to be better outcomes in people on these medications. We can also look at the percentage of people chronically medicated with these medications in the general population and compared with the percentage among hospital admissions of COVID-19 (SARS-CoV-2) infected patients presenting with serious symptoms. If the latter percentage would be found to be significantly smaller, this would support the notion that the medications confer protection from severe symptoms among SARS-CoV-2 infected individuals and contribute to our ongoing gain in knowledge crucial for reducing the mortality and morbidity of SARS-CoV-2.Third, we could design a therapeutic intervention to examine if placing people on these medications is helpful. This is an approach that could likely be done now. It certainly should be done moving forward if not being done already in a retrospective fashion.  

https://onlinelibrary.wiley.com/doi/full/10.1002/ddr.21656