Comment by delhanty | Hacker News Reader

Comment by delhanty | Hacker News Reader

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This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that ACE inhibitors are a potential risk factor for fatal Covid-19 in those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular disease:

>The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR 10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the SARS outbreak in 2003.

> ...

>On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4].

>

>On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5].

Edit: thank you philipn for your twitter link.

[0] https://www.bmj.com/content/368/bmj.m810/rr-2

Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon:

https://twitter.com/__philipn__/status/1235756671852589056

It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2.

This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts.

The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post.

Will be posting a summary to my twitter soon.

I am propably among the most ardent critics of twitter and social media when it comes to Corona. And then comes a guy like you. Stuff like that should be among every top comment, everywhere when it comes to this. Along side the WHO situation reports and guidelines. So, thank you!

A few days ago I started taking a low dose of an OTC ACE inhibitor in order to upregulate my ACE2 receptors. This is what the literature that was written before the current epidemic about surviving novel Coronavirus pandemics says to do, and the new evidence that comes out each day is actually validating this strategy.

It's only the scientists who didn't start studying Coronaviruses until two weeks ago who seem to think that having ACE2 receptors is dangerous.

>OTC ACE inhibitor

Which country are you in?

USA.

Hmm...according to doc friend there are no OTC ACE inhibitors in USA.

Edit: Luckily I own several acres of Hawthorn bushes.

I think Hawthorn or hibiscus. You can get them certified as USP or cGMP, and/or independently tested by Consumer Labs.

I'm not 100% sure on the mechanism of action on Hawthorn. I've read that it's an ACE inhibitor, but I don't have a good source. But I can see at the very least that it's an elastase inhibitor, which is supposed to be protective against ARDS.

edit: I think proanthocyanidin is the component that is supposed to be an ACE inhibitor.

Sources:

https://www.ncbi.nlm.nih.gov/pubmed/12866623

https://www.phcogj.com/sites/default/files/PharmacognJ-10-25...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612254/

> I think Hawthorn or hibiscus.

Do you take them like some herbal remedies (grind it, add honey etc.etc) or do you process it in a lab?

I'm just taking some expired Hawthorn pills that I happened to have lying around the house. In my case I don't have high blood pressure to begin with, so I'm just taking about 1/3rd of the recommended dose and then periodically checking to ensure that my blood pressure isn't getting dangerously low.

People make their own hawthorn jam and jelly though, so it isn't excessively dangerous, but on principle it's probably better to take a conservative approach, or at least one that's commensurate with the initial risk.

Because I'm in NYC we actually have them growing everywhere because they are one of a handful of approved small-sized street trees, and they're in all the parks, but regardless it's easier just to buy as a supplement.

Sounds just as risky as getting infected. :) Be careful and good luck!

Asking as a lay man, are you taking this as a preventive measure?

Yes. My risk of death is supposedly nominal, but I want to avoid any lung damage.

I'm taking a low dose though, in part to hedge my bets, and in part because I don't want to bleed out if I get into a bike accident.

If the virus is infecting a cell through the ACE2 receptor, wouldn’t upregulating the receptor just increase the risk of infection?

As per the paper, you want to either block the receptor or down regulate it.

That definitely could be true, but from what I've read it probably isn't. One of the ways the virus kills people is by destroying their ACE2 receptors, which your lung cells need to function. If you blocked them all, your lung cells would die anyway. So as long as the virus can enter your lung cells, you might as well prevent it from killing them by making extra ACE2 receptors. That's the theory anyway.

There are also many other ways you can block the virus from entering your lungs that don't involve downregulating your ACE2 receptors.

Could you possibly comment on this, as it strikes me as odd, regarding the surprising characteristics of smokers from this study from China:

https://www.nejm.org/doi/full/10.1056/NEJMoa2002032

86.9% of non severe cases had never smoked 77.9% of severe cases had never smoked

Contrasted with 1.3% and 5.2% in former smokers and 11.8% and 16.9% in current smokers.

I think the table in that paper is just confusing. The parenthesized numbers are for portion of the total number of people, rather than the portion of that category.

For instance, there are 137 current smokers. 108 are listed as non-severe. 29 are listed as severe. This means 108/137 = 79% non-severe, 29/137 21% severe.

Never smoked: 927 total, 793/927 non-severe (86%), 134/927 severe (14%).

Hope that makes sense. That table confused me too. Don't start smoking!

For context, around 60% of men in China smoke. Your proximate interpretation of the numbers is correct, but I think the real question is where are there so few smokers in the data. (And whether smoking confers some sort of protective effect by upregulating ACE2 receptors.)

I'm fairly out of my depth here, but it's somewhat relevant to my personal situation:

When this came up for discussion on HN a few days ago, I was initially confused, as some of what I read seemed to suggest that taking e.g. lisinopril could possibly increase the risk of an infection because it seems to increase the expression of ACE2 receptors that are used by the virus to infect cells.

On the other hand, some of what I read seemed to suggest that ACE inhibitors (e.g. lisinopril) could have a therapeutic benefit. The virus is going to inactivate a bunch of ACE2 receptors through the course of infection. Since ACE2 receptors inactivate angiotensin, that would leave a lot of active angiotensin floating around, which is potentially very bad. ACE inhibitors would seem to help here because they inhibit the active form of angiotensin from being created in the first place.

Now I'm wondering: Is it possible that taking lisinopril could increase the risk of serious infection for those of us not yet infected, but also could reduce the severity of an active infection?

I agree. There is a +6% increase in COVID-19 mortality for those with hypertension. Assume all were on BP meds. They're cheap, & doctors usually insist. If ACEs or ARBs were protective, it should be more like -6%. Right? Losartan = 400% more ACE2, Lisinopril = 100% more ACE2.

Elderly people are usually on BP meds. Diabetics are frequently prescribed Losartan to protect their kidneys. I know. I am a diabetic, and was prescribed it for that reason and also for high BP.

As a diabetic over 50 with high BP I have a greater interest than most. Especially since my wife was exposed to coronavirus, is sick, and I am starting to feel unwell.

Stopped taking losartan yesterday. Have some tenofovir lying around and might start taking it. It's the only antiviral I was able to get my hands on. Hopefully my chloroquine arrives in the mail soon.

I read a paper that suggested caffeic acid was the anti-viral component of elderberry extract that was actually inhibiting HCoV-NL63 viral attachment and infection of human lung cells in vitro (Virus Research, 273 (2019)197767). This paper speculated that caffeic acid binds to ACE2 and inhibits viral attachment and infection via this route. Another paper suggested 95% absorption in humans dosed with 500 mg in 200 mL of hot water. A third paper that looked at 2-year study in SD rats suggested pro-carcinogenic properties, but many other papers suggest anti-oxidant/anti-inflammatory/anti-carcinogenic properties. If I start to come down with it, I think I'm going to do a 500 mg caffeic acid dose.

Could someone explain this in laymen terms please.

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