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 diarrhoea, 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.

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 angiotensin converting enzyme (ACE) inhibitors; however,
treatment was not assessed in either study.

*Author: Dr
Peter Lin – Director, Primary Care Initiatives, Canadian Heart Research Centre;
Medical Director, LinCorp Medical Inc.

SOURCE: https://www.practiceupdate.com/c/98006/1/24/?elsca1=emc_enews_daily-digest&elsca2=email&elsca3=practiceupdate_gastro&elsca4=gastroenterology&elsca5=newsletter&rid=NTU2MjE4MTIzNzES1&lid=10332481

REFERENCE:
Fang et al: Are patients with hypertension and diabetes mellitus at increased
risk for COVID-19 infection? 
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext