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Journal Scan / Commentary · March 22, 2020

Are Patients With Hypertension and Diabetes Mellitus at Increased Risk for COVID-19 Infection?

The Lancet Respiratory Medicine

TAKE-HOME MESSAGE

• In this commentary, the authors take up the topic of comorbidities of patients with confirmed COVID-19, basing their discussion on three recently published studies.

• Although the most frequent comorbidities reported in these studies, including diabetes and hypertension, are frequently treated with ACE inhibitors, none of the three studies assessed the treatment related to the comorbidities.
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Written by

 

 

Peter Lin MD, CCFP

COVID-19 and ACE-i and ARB

On March 11, 2020, Lancet published a correspondence piece entitled, "Are patients with hypertension and diabetes at increased risk for COVID-19 infection?"

The authors pointed out that the patients with more severe disease were more likely to have hypertension and diabetes. They then explained that the COVID-19 virus uses its spike proteins to attach to the ACE2 (angiotensin-converting enzyme 2), which is sitting on the epithelial cells of the lung. This is how the virus is invited into the lung cells and then it takes over the factories to make copies of itself.

Then they said that ACE-i and ARBs causes an upregulation of ACE2 and, "consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19."

This statement is a hypothesis and completely unsubstantiated but of course some people read it as factual. Then they go on to say, "Based on a PubMed search on Feb 28, 2020, we did not find any evidence to suggest that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients."

So the authors went from a hypothesis all the way to a recommendation of stopping ACE-i and ARBs within a 1-page document. They did not show any data demonstrating that being on an ACE-i or ARB had worse outcomes. They also did not consider the consequences of stopping ACE-i or ARBs, which could lead to increase in CV events, worsening of heart failure, and renal complications.

Interestingly, other researchers have pointed out that there is a soluble version of ACE2, which is not on the cell membrane, so this could act as a decoy for the virus to bind to so the lung cells would be spared. This would mean that an increase in soluble ACE2 might be protective. So if ACE-I and ARB increase soluble ACE2, then they may actually be beneficial. Now, we don't know if the soluble ACE2 can even get to the virus considering the virus is coming in from the airway side, but if there is soluble ACE2 in the fluid layer that is just on top of the lung cells, then there might be a protective effect.

In other research, they have shown that angiotensin II is needed for lung fibrosis to occur. Both COVID-19 and SARS patients that recovered had excessive scaring of their lungs. In animal models, when there is no angiotensin II, the scarring does not happen. That ACE2 breaks down angiotensin II, so less angiotensin II might mean less fibrosis. So if ACE-i and ARBs increase ACE2 then that could be protective against lung fibrosis and further damage.

Also it turns out, the SARS virus used the ACE2 as its entry point as well, and we never saw any detrimental effects of being on ACE-i or ARBs during the SARS pandemic.

I cite all these different studies and facts to point out that there are many aspects that we need to consider, and that that over simplification is not always wise.

That is why the American Heart Association, the Heart Failure Society of America, and the American College of Cardiology put out a statement on March 17, 2020. The AHA, the HFSA and the ACC recommend "continuation of angiotensin converting enzyme inhibitors (ACE-i) or angiotensin receptor blocker (ARB) medications for all patients already prescribed for indications such as heart failure, hypertension or ischemic heart disease."

They go on to say, "We have reviewed the latest research – the evidence does not confirm the need to discontinue ACE-i or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-i or ARB treatment regimens."  They concluded by saying, "These recommendations will be adjusted as needed to correspond with the latest research."

Think of a patient who has COVID-19. The virus has already gained entry into the cell, so stopping ACE-i or ARBs would not reduce the COVID-19 risk, but it would increase the CV and renal risk. So keeping them on therapy makes sense. Now, think of your patients not infected with COVID-19. Stopping ACE-i or ARBs would put them at high risk of CV and renal complications. If they never get COVID-19, then we would have increased their risk for no reason.

Basically, this means that we should keep our patients on their ACE-i or ARB. One caveat is that if they are dehydrated, vomiting, or experiencing diarrhea, then as part of the sick day medications, we should be thinking about holding the ACE-i or ARB. But in all other cases, keep it on. We can protect our patients from virus by getting them to protect their personal borders, but we should let the ACE-i and ARBs do their job of protecting the CV and renal systems.

Abstract

The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues were cerebrovascular diseases (22%) and diabetes (22%). Another study included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study, of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Notably, the most frequent comorbidities reported in these three studies of patients with COVID-19 are often treated with angiotensinconverting enzyme (ACE) inhibitors; however, treatment was not assessed in either study.

The Lancet Respiratory Medicine

Are Patients With Hypertension and Diabetes Mellitus at Increased Risk for COVID-19 Infection?

Lancet Respir Med 2020 Mar 11;[EPub Ahead of Print], L Fang, G Karakiulakis, M Roth 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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