SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2 • Hacker News Board

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#91

Post by lamontcg » Mon, May 03, 2021, 8:18 AM UTC

beagle3 wrote: post #74

lamontcg wrote: post #63

Earlier quoted context omitted.

The rate of MIS-C in children is on the order of 1 in 20,000. So acute myocarditis (which goes away and does not produce lasting damage) at that level is entirely an acceptable risk. You're under the impression that either the vaccine must be perfectly safe and/or that the disease is perfectly safe for young people. Both of which are false.

I don't know how you read that into what I wrote. It doesn't have to be perfectly safe; but it has to be significantly safer if you get it, than the disease if you get it -- which is, in fact, the case for all regularly administered vaccines (MMR, polio, tetanus, etc.), and comes with a warning and explanation for those that aren't (our pediatrician made sure we understand the rotavirus vaccine before we gave it to o…

The MIS-C rate is 1-in-12,500 per the CDC:

https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e3.htm?s_cid=mm...

1-in-3 hospitalizations require admittance to the ICU.

The study you cite is total incidence.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#92

Post by Pyramus » Mon, May 03, 2021, 9:04 AM UTC

beagle3 wrote: post #78

Pyramus wrote: post #70

Earlier quoted context omitted.

Not disagreeing with your general message regarding individual risk assessment based on age, sex, health etc. What I will say though is that you seem to be comparing to the baseline scenario "Covid stops spreading". After one year of Covid (and its mutations) that baseline simply doesn't exist (any more). Instead we are in a no-win situation: (a) We keep lockdowns/non-pharmacological measures and border closures, (b)…

No, I'm not comparing to "covid stops spreading", but I'm also not assuming (as you seem to be) "everyone will eventually get it in the way whoever got it so far got it". > Each scenario has associated cost. There are other scenarios, e.g. https://www.ox.ac.uk/news/2021-02-09-common-asthma-treatment... shows a cheap widely available steroid inhaler has comparable efficiency to vaccines in the KPIs studied by the Pfiz…

> There are other scenarios, e.g. https://www.ox.ac.uk/news/2021-02-09-common-asthma-treatment... shows a cheap widely available steroid inhaler [...]

That is a good point, I should have defined the category more broadly as 'pharmacological interventions,' of which vaccines make up the biggest and best-studied subcategory (to date).

> That's ... not been shown. The Israeli study I linked to above (a report of it) says this assertion might be wrong for Pfizer for the sizable group of 16-30 ; The British think that's not true for AZ under age 30 ; many countries in the EU think that's not true for AZ under the age of 50 ; Norway thinks that's not true for frail elderly.

Yes and no. Yes, E.g. for AZ there will be a threshold (say 30) at where Covid risk equals vaccine risk. At that point, both risks are very small, to the point that it's more dangerous to drive to the appointment by car. No, when EMA says no AZ under 50 (in Germany it's 60) that's because for that age group we have other vaccines available. Still, even for a 40 year old female it is safer to get AZ than Covid. For that reason current vaccines are safer for most people but not all. Even when they are not safer than Covid, data suggests they are still very safe.

> And basically, we only have short term safety data (pfizer: less than a year for 20K people, less than 6 months for the rest) [...]

I believe you do know that Pfizer/Biontech, Moderna, AZ all started in 04/2020, so we have data for 12m+. As a comparison safety data for Covid is only 6m older.

> I linked a BMJ+Science article that showed for a similarly EUAd vaccine, "Pandemrix" in 2009 that it took over a year to figure out that it was causing narcolepsy and worse than the flu it was supposed to stop.

Yes, Pandemrix is still remembered, especially in Northern Euope, and one reason why regulators are have been super careful, to the point where it didn't make sense to halt vaccination campaigns, see e.g. AZ blood clots. In general we expect side effects of vaccines to have an onset shortly after vaccination, and that has been also true for Pandemrix. However to detect two rare events, say narcolepsy and 5x narcolepsy, you need a lot of data. In the context of H1N1 and narcolepsy, this paper is super interesting [1] https://med.stanford.edu/content/dam/sm/narcolepsy/documents...

> It could be that for those 80%, that response would be enough to stop the virus before it can get systemic traction, [...]

That's not the conclusion of the paper and hopeful speculation. If you mean by 'systemic reaction' the replication of the virus in the host, it's demonstrably false.

I totally get the concern about 'unknown unknowns' but looking at the safety data you are currently engaging in lifestyle choices or are taking medication that are way riskier than current Covid vaccines.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#93

Post by collyw » Mon, May 03, 2021, 2:26 PM UTC

russfink wrote: post #39

Would someone please dumb this down for me?

The spike protein alone can cause damage, in other word you don't need a coronavirus infection. The vaccines make your body generate this protein.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#94

Post by collyw » Mon, May 03, 2021, 2:30 PM UTC

beagle3 wrote: post #21

retrac wrote: post #13

Earlier quoted context omitted.

It causes the body to produce it in a limited, fixed quantity in proportion to the number of viable RNA strands that make it into a cell, largely localized at the injection site. Just a guess but this probably means its risk is extremely limited. The wild virus causes this protein to be produced without check. It wouldn't just be the mRNA vaccines, anyway. The viral vector ones, as well as the inactivated virus, and…

Indeed. But it's a nontrivial question of numbers. The vaccine has to be orders of magnitude safer than the virus, because (essentially) everyone will get the vaccine, but only some will get the disease. E.g. it might be harmful to vaccinate people in New Zealand and Australia at this point, because for now they cannot get the virus. What these papers (there are 3 independent ones showing very similar results, all co…

> The vaccine has to be orders of magnitude safer than the virus

Given that there are vast differences in outcomes in different age groups to the virus, surely that depends on the age group you are targeting. Pushing the vaccine onto children, who are at practically no risk seems morally wrong to me.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#95

Post by collyw » Mon, May 03, 2021, 2:34 PM UTC

podgaj wrote: post #60

So if ACE2 is downregulated, and ACE2 uses zinc as a cofactor, why are they not looking at high doses of zinc as a treatment? https://www.uniprot.org/uniprot/Q9BYF1

Proponents of hydroxychloroquine have been saying that it needs to be taken with zinc to be effective.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#96

Post by rolph » Mon, May 03, 2021, 2:47 PM UTC

darkerside wrote: post #80

rolph wrote: post #49

Earlier quoted context omitted.

in general terms yes, there is no real hard number on minimal number of viral particles required to result in infection, its most likely a small number compared to the number of vaccine particles in a dosage. assuming 30 micrograms dosage in a volume of 300 microliters that is a very large number of particles in one place. this is not a lot of vaccine, but this [30micrograms] would be quite a lot of viral particles.…

Should we expect localized endothelial inflammation in that case?

no you shouldnt, the vaccine is going into muscle tissue, the muscle will experience inflammation due to the presence of the vaccine, this means things are working as planned, and the tissue is opening up to allow the immune system access to the site. you wont find endothelium in the muscle tissue, and you wont get a systemic distribution of vaccine or free floating spike protien.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#97

Post by beagle3 » Mon, May 03, 2021, 10:43 PM UTC

Pyramus wrote: post #92

beagle3 wrote: post #78

Earlier quoted context omitted.

No, I'm not comparing to "covid stops spreading", but I'm also not assuming (as you seem to be) "everyone will eventually get it in the way whoever got it so far got it". > Each scenario has associated cost. There are other scenarios, e.g. https://www.ox.ac.uk/news/2021-02-09-common-asthma-treatment... shows a cheap widely available steroid inhaler has comparable efficiency to vaccines in the KPIs studied by the Pfiz…

> There are other scenarios, e.g. https://www.ox.ac.uk/news/2021-02-09-common-asthma-treatment ... shows a cheap widely available steroid inhaler [...] That is a good point, I should have defined the category more broadly as 'pharmacological interventions,' of which vaccines make up the biggest and best-studied subcategory (to date). > That's ... not been shown. The Israeli study I linked to above (a report of it) sa…

> so we have data for 12m+. As a comparison safety data for Covid is only 6m older.

We have data for 12m, but only for a very small population (22k in Pfizer, less in others IIRC). You are unlikely to see a 1:20,000 general population risk (as indicated by the Israeli study) in a 22k "volunteer, must be quite healthy" experiment. Unsurprisingly, there are no deaths in the pfizer trial - neither vaccine nor placebo arm (and no severe disease past day 73 in the placebo arm) That's the 12m data we have.

No, we have 6m real world data for the vaccine, and 18m real world data for the virus. That's .. quite a difference.

> However to detect two rare events, say narcolepsy and 5x narcolepsy, you need a lot of data.

Indeed, which is why I am puzzled -- given that you are very much aware of the details -- that you can keep claiming that "the vaccine is less dangerous than the virus". You have proof from just 11 years ago where it took over a year of real world use to figure otherwise. What makes you think this time is different?

> That's not the conclusion of the paper and hopeful speculation

True. Also, the long term safety of covid vaccines is not a conclusion of any research and is hopeful speculation. And yet, people get no challenge for assuming that, despite counterexamples like Pandemrix.

> you are currently engaging in lifestyle choices or are taking medication that are way riskier than current Covid vaccines.

While that's true, that's also true for my subjective risk from COVID19 (and that's also true for the vast majority of 20-40 year olds). Would you consider that a good reason to ignore covid completely, and not take any precautions? If so, then - why do you care about the vaccine?

If it isn't a good reason -- and I don't think it's a good reason to ignore covid -- then ... why is the same argument not applicable to the covid vaccines safety?

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#98

Post by beagle3 » Mon, May 03, 2021, 11:03 PM UTC

lamontcg wrote: post #91

beagle3 wrote: post #74

Earlier quoted context omitted.

I don't know how you read that into what I wrote. It doesn't have to be perfectly safe; but it has to be significantly safer if you get it, than the disease if you get it -- which is, in fact, the case for all regularly administered vaccines (MMR, polio, tetanus, etc.), and comes with a warning and explanation for those that aren't (our pediatrician made sure we understand the rotavirus vaccine before we gave it to o…

The MIS-C rate is 1-in-12,500 per the CDC: https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e3.htm?s_cid=mm... 1-in-3 hospitalizations require admittance to the ICU. The study you cite is total incidence.

I was referring to total incidence, because approved vaccines have total incidence (Israel, where I now reside, has >84% of eligible population already vaccinated), so that's what you should compare to when considering vaccine adverse events vs. disease adverse events.

But something doesn't compute;

1:12,500 COVID incidence vs. 1:50,000 total incidence means 1 in 4 kids in the US has confirmed covid, despite less than 10% of the US population being verified (32.4M as of this second).

If we extrapolate the 1:12,500 number to the whole population (assuming 10% of the kids are confirmed), it's 1:125,000 for MIS-C in disease, vs. 1:20,000 myocarditis with vaccine. I'm not sure it's valid extrapolation (and I suspect your data, from July, is very outdated), either way -- it is not possible, based on this data, to claim that it is clearly beneficial to vaccinate children.

The data I'm familiar with DOES show that at age > 50 there are clear benefits. But, especially with respect to things like age, obesity and other attributes, it is very far from "one size fits all".

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#99

Post by lamontcg » Tue, May 04, 2021, 4:15 AM UTC

beagle3 wrote: post #98

lamontcg wrote: post #91

Earlier quoted context omitted.

The MIS-C rate is 1-in-12,500 per the CDC: https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e3.htm?s_cid=mm... 1-in-3 hospitalizations require admittance to the ICU. The study you cite is total incidence.

I was referring to total incidence, because approved vaccines have total incidence (Israel, where I now reside, has >84% of eligible population already vaccinated), so that's what you should compare to when considering vaccine adverse events vs. disease adverse events. But something doesn't compute; 1:12,500 COVID incidence vs. 1:50,000 total incidence means 1 in 4 kids in the US has confirmed covid, despite less tha…

Only 1 out of 3-4 infections are confirmed. That would increase the actual number of infections to 30%-40% which is in-line with having at least 1 in 4 children having been infected.

Current total incidence is the wrong metric to use since tht will increase over time. Not using vaccines would mean 3x or so more infections before some level of herd immunity was reached.

It would also give the virus another 3x the number of die rolls towards mutating as well, with pressure to increase transmissibility which should come with an increase in virulence.

And my 1-in-12,500 numbers were before the virus started to mutate to increase transmissibility/virulence. Those numbers will probably drop.

Re: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

#100

Post by beagle3 » Tue, May 04, 2021, 7:24 AM UTC

lamontcg wrote: post #99

beagle3 wrote: post #98

Earlier quoted context omitted.

I was referring to total incidence, because approved vaccines have total incidence (Israel, where I now reside, has >84% of eligible population already vaccinated), so that's what you should compare to when considering vaccine adverse events vs. disease adverse events. But something doesn't compute; 1:12,500 COVID incidence vs. 1:50,000 total incidence means 1 in 4 kids in the US has confirmed covid, despite less tha…

Only 1 out of 3-4 infections are confirmed. That would increase the actual number of infections to 30%-40% which is in-line with having at least 1 in 4 children having been infected. Current total incidence is the wrong metric to use since tht will increase over time. Not using vaccines would mean 3x or so more infections before some level of herd immunity was reached. It would also give the virus another 3x the numb…

I don’t have time now to check this, but most research I know shows mutations happen significantly more often in the immune compromised even when vaccinated on one hand, and that while increased transmissibility is associated with a strain or too, that’s not remotely true in general or about virulence.

Regardless, if I take your numbers, assuming 33% had the virus, we’re talking about very similar toys incidence at saturation (the 1:20,000 - 1:10,000 range, the error bars are huge), so it is far from obvious that the existing vaccines are safer than the disease.

It is true for all approved vaccines I’m familiar with; but you can’t claim that for any of the Sarscov2 vaccines based on available data.

What I’m really surprised is that somehow the default mindset changed from “we have to establish safety to use” to “we have to establish non-safety to not use”. Am really puzzled by that.