Hypothetical Link between some widely used Blood Pressure Medications and Increased Sensitivity to COVID-19 Infection.

The topic of this article is still a hypothesis, and I am updating it as important news comes in.  However it will take some time to confirm or refute it.  People on these medications should take prudent social distancing measures in the interim.  There is no current consensus to change your medications however, and stopping blood pressure medication can be dangerous.  Some medical authorities are already disputing this hypothesis as noted below, but others call for more research.


 

Last significant update of the main text on Monday, 3/16 at 11:55 AM Pacific Daylight Time.  Please see the Comments section following the main article for additional ongoing details.

A possibly very important article appeared in the Lancet medical journal recently:

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext

In brief, the article states that people treated with specific classes of blood pressure medications (meds that are also used on some people with diabetes) have increased amounts of the ACE2 protein that the novel coronavirus binds to when it attacks lung cells.

The article states “We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19.

Note, of course, the word “hypothesise” (sic – hypothesize, unless this is UK spelling – the corresponding author is from Switzerland).  This hypothesis is not proven, but seems very plausible.

This hypothesis is similar to a question that I raised on local social media a few days ago in regards to ACE inhibitors (ACEI), especially lisinopril which causes “lisinopril cough,” at

https://nextdoor.com/post/139950824

[Sorry, but the link above will only work for people in my nearby neighborhood location (San Mateo, CA) with Nextdoor accounts.]

A local doctor, Dr. Raymond Hong who is an allergist, saw this post and commented that he believed that only Angiotensin Receptor Blocker (ARB) drugs increased the number of ACE2 receptor proteins that the novel coronavirus attacks, not ACE inhibitors.  He also thought that this was a very interesting hypothesis that needed additional research.

He cautioned (I added bolding in his quote for emphasis):

“Although this sounds concerning, in no way am I advocating stopping or switching angiotensin receptor blockers (or ace inhibitors) or discussing this with your doctor quite yet. But I agree we should definitely be looking at the patients with severe COVID-19 disease to see what medical conditions they have, and if they have hypertension, what medications they are on. Any positive findings might help spur more caution and studies. There may be multiple factors involved and I just thought I’d respond to your question in a responsible manner.”

Personally, I (Kristofferson) should note that changing medications will NOT cause the levels of these lung proteins that the virus attacks to decrease overnight.  If this hypothesis turns out to be correct (and unfortunately its resolution may take too long to help people currently at risk for COVID-19), my take is that people on these medications should take extra precautions to avoid exposing themselves to sick individuals.  This undoubtedly means hunkering down at home given the latest developments.

This hypothesis could also explain why young people might develop severe coronavirus cases – they might be at risk if they have elevated ACE2 levels as a result of using ACEI/ARB medications.

A new JAMANetwork review article (link added near the end of this article) states that it is possible that either genetics or the high rate of smoking among Chinese men may have increased their ACE2 levels and made them more susceptible to the disease, but, again, this is not yet proven:  “The ACE2 enzyme is expressed in type II alveolar cells, and some unconfirmed data suggest that Asian males have a large number of ACE2-expressing cells in the lung, which may partially explain the male predominance of COVID-19. However, other factors such as a higher prevalence of smoking among men in China may explain the difference in the sex distribution of the disease.”

Dr. Hong has just (3/13/2020 5:45 PM PDT) notified me of the following news:

I think it’s too early to make recommendations about switching. In fact because of social media posts similar to mine, there has been concern about patients stopping their blood pressure medications. The European Society of Cardiology published a position statement to not stop ace inhibitors or arbs as there is no evidence to support this. They stated there is evidence in animals that these medications might even be protective against serious lung complications from COVID-19. So they recommended against making any changes.

Here is the official statement that he notes above:

Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers

This ESC article clearly contradicts The Lancet article and states:

This speculation about the safety of ACE-i or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it. Indeed, there is evidence from studies in animals suggesting that these medications might be rather protective against serious lung complications in patients with COVID-19 infection, but to date there is no data in humans.

The Council on Hypertension of the European Society of Cardiology wish to highlight the lack of any evidence supporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak.

The Council on Hypertension strongly recommend that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection.

Important other expert opinions on this hypothesis can be found in the following link.  Some of these experts say that the jury is still out:

Expert reaction to questions about high blood pressure, diabetes, and ACE inhibitor drugs, and risk of COVID-19 infection

The following shows the tremendous complexity of this whole problem. Here is an interesting tweet from a doctor at Johns Hopkins. This doctor is working on novel therapeutics. He states in the tweet: “My recommended COVID19 treatment algorithm is starting patients who have more than mild symptoms or in high-risk category with: 1. Antiviral (chloroquine or hydroxychloroquine) 2. Losartan or other ARB (combat lung injury). Both proven w/ data, the latter acting on ACE2 pathway.'”  In the thread to his tweet he answers the concern about ARBs increasing ACE2 levels and claims the situation goes into reverse AFTER infection sets in as the viral infection causes ACE2 levels to drop.  Thus ARBs are helpful AFTER the fact: “it is beneficial for these drugs to increase ACE2. The lack of ACE2 leads to pulmonary edema.”  This looks like a case of initially damned if you do, but then damned AFTER if you don’t…

In conclusion, one should clearly not make any changes to your current medications while this debate plays out, but, in my personal opinion, we do not yet know what the final outcome will be, and the pandemic could be over before we do.  That is why I personally advise readers who take these medications to practice “social distancing” with particular diligence until the science is finally settled.

The following excellent JAMANetwork review article (which has section headings on the virus, epidemiology, clinical characteristics, case-fatality rates, screening and testing, clinical care and treatment, and prevention and infection control) just came to my attention via a tweet from Dr. Sanjay Gupta of CNN:

https://jamanetwork.com/journals/jama/fullarticle/2762510

Please scroll down to the Comments section below for further questions and information.

Author: David Kristofferson

Retired scientist, teacher, bioinformatician, IT director, software product manager, AAAS Fellow, avid cyclist (7690 miles and 724,300 feet of climbing in 2015), backpacker, you name it! Current avocation is tutoring high school students near San Mateo, CA in mathematics, physics and chemistry. Please see the Bio link in the right sidebar for my detailed background information.

4 thoughts on “Hypothetical Link between some widely used Blood Pressure Medications and Increased Sensitivity to COVID-19 Infection.”

  1. Dr. Patrick Soon-Shiong: The virus has figured a way to enter our lungs by an ingenious docking mechanism onto a receptor ACE2 on the surface of cells in the lung… this is the Achilles heel which will allow us to block its entry. #coronavirus #ACE2 #covid19

    Like

    1. Yes, ACE2 is supposed to be the attachment point. I don’t think I would use the anthropomorphisms that the doctor used in your quote though. Many viruses are engulfed by cells after binding to particular cell surface proteins and, the last time I looked, viruses have not yet developed brains 😉.

      That said, I came across the following interesting therapeutic research paper this AM from Johns Hopkins:

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/

      Like

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