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

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

#41

Post by Izkata »

maxerickson wrote: post #25
beagle3 wrote: post #21

Earlier quoted context omitted.

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…

We are getting close to 2% of the planet having a confirmed case. New influenza vaccines (using cell lines) were approved after use in 15,000 people, ~10 years ago: https://www.fiercepharma.com/vaccines/novartis-receives-fda-... Are you overestimating the safety testing done on other vaccines? Of course these are the first widely used vaccines for corona viruses and use new technologies to boot, so there's a lot more…

> Basel, November 20, 2012 – Novartis announced today that the US Food and Drug Administration (FDA) approved the use of Flucelvax® (Influenza Virus Vaccine), the first cell-culture-derived vaccine, for individuals 18 years of age and older3.

> A multinational, randomized, observer-blinded, placebo-controlled trial was performed to assess clinical efficacy and safety of Flucelvax during the 2007- 2008 influenza season in adults aged 18 to 49 years in the US, Finland and Poland3.

They took ~4 years to approve it, sounds like they were more cautious for Flucelvax.

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

#42

Post by rzz3 »

yborg wrote: post #36
briefcomment wrote: post #31

Earlier quoted context omitted.

This makes the analogy even more appropriate. We know the spike protein is harmful in some amount, but we think a small enough amount produced forever should be safe. Maybe we'll learn otherwise.

Why do you think it is produced forever? The mRNA quickly degrades in the body and the injected cells will stop producing the spike protein. That's why there has to be a second injection.

Is there a source? 100% believe you, but due to the conflicting posts I’d love to read the source (and I don’t know what to Google). Thanks!

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

#43

Post by _greim_ »

rolph wrote: post #9
unanswered wrote: post #3

If this is a function of the spike protein, doesn't that mean the mRNA vaccines cause this effect as well?

this is a relevent question, the difference between the two cases, is that the virus is mobile and has opportunity to travel through the entire endothelial tissue structure, interacting with many molecular types and situations the vaccine causes a small volume of stationary cells in the muscle mass of the shoulder to express the S protien on the surface, staying in place but providing signal to the immune system [adn…

Interesting. Is there a significant difference in total number of viral particles versus vaccine particles your cells are exposed to, over the course of the infection/vaccination?

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

#44

Post by 908087 »

stevemk14ebr wrote: post #20

Can someone ELI5 please? My field is low level computer systems, and unfortunately that knowledge does not extend to low level physiological processes!

Don't let that stop you from pretending to be an expert in other fields. It doesn't stop anyone else here.

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

#45

Post by treeman79 »

lc9er wrote: post #28
dcow wrote: post #26

Earlier quoted context omitted.

My partner developed inflammation (resembling gottron papules) on her knuckles a few weeks after receiving the first moderna dose. She now (few days later) has developed a shoulder rash where the vaccine was injected. It’s very curious.

My spouse, who suffers from an autoimmune disorder, suffered similar symptoms. Severe enough that she won’t be able to get the second dose. My understanding (from her doc) is that this is a known, but uncommon side effect for people with autoimmune conditions.

Does get the uncommon side effects of medication much?

Have an autoimmune, and I get most of the rare side effects of medications.

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

#46

Post by darkhorn »

Alex3917 wrote: post #5

Yeah we've known this for over 10 years, zero surprise here. There were literally popular books written saying that this would be the mechanism of action for novel coronavirus pandemics (and how to treat them) years before the current pandemic even started, e.g.: https://www.amazon.com/Herbal-Antivirals-Remedies-Resistant-... Here is the direct quote from the book, published in 2013: "Once receptors on these cells ar…

So, some people were studying new kinds of viruses?

Oh, okay, yeah, here https://www.wired.com/2013/05/h5n1-h1n1-reassortment/

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

#47

Post by piva00 »

Alex3917 wrote: post #38
dctoedt wrote: post #29

Earlier quoted context omitted.

Not my field (I can spell DNA) but this recent piece seemed of interest. FTA: "A large meta-analysis provides yet more evidence that ACE inhibitors and angiotensin receptor blockers (ARBs) pose no harm to patients with COVID-19 and may even be associated with protective benefits, particularly in patients with hypertension." https://www.tctmd.com/news/continue-ace-inhibitorsarbs-covid...

Also women and smokers are underrepresented among hospitalized patients, which was the first confirmatory evidence from over a year ago.

I know nothing about physiology (apart from up to high school level, so... Nothing), could you expand on how smokers and women relate to ACE-2?

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

#48

Post by Kubuxu »

rzz3 wrote: post #42
yborg wrote: post #36

Earlier quoted context omitted.

Why do you think it is produced forever? The mRNA quickly degrades in the body and the injected cells will stop producing the spike protein. That's why there has to be a second injection.

Is there a source? 100% believe you, but due to the conflicting posts I’d love to read the source (and I don’t know what to Google). Thanks!

(m)RNA is inherently unstable in our body: https://en.wikipedia.org/wiki/Messenger_RNA#Degradation

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

#49

Post by rolph »

_greim_ wrote: post #43
rolph wrote: post #9

Earlier quoted context omitted.

this is a relevent question, the difference between the two cases, is that the virus is mobile and has opportunity to travel through the entire endothelial tissue structure, interacting with many molecular types and situations the vaccine causes a small volume of stationary cells in the muscle mass of the shoulder to express the S protien on the surface, staying in place but providing signal to the immune system [adn…

Interesting. Is there a significant difference in total number of viral particles versus vaccine particles your cells are exposed to, over the course of the infection/vaccination?

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.

something to keep in mind is the fuzz of biological systems. molecular processes can have more than one outcome but there is a general bias toward an overall stability, so when a vaccine is produced, there is a certain amount of fuzz to it in the form of particles that dont assemble correctly or ar otherwise non desireable, processing the vaccine keeps these characters to a minimum.

the same thing happens to the virus, the fuzz portion being in someway unable to replicate or enter a cell, just out of the way the fuzzy dice roll.

so its hard to pin down a number of minimally effective dose for either case, however virus amplifies past the original dose, and spreads to mutiple locations, signaling any molecular system that can be bound to, in this case vast preference being given to ACE-2, resulting in perturbation of the RAS system and the now stereotypic covid symptoms

so viral particles amplify over time, and over a spatial distribution, vaccine particles stay in site and dont replicate and dont migrate to interact with other cells in the tissue or throughout the body.

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

#50

Post by beagle3 »

maxerickson wrote: post #25
beagle3 wrote: post #21

Earlier quoted context omitted.

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…

We are getting close to 2% of the planet having a confirmed case. New influenza vaccines (using cell lines) were approved after use in 15,000 people, ~10 years ago: https://www.fiercepharma.com/vaccines/novartis-receives-fda-... Are you overestimating the safety testing done on other vaccines? Of course these are the first widely used vaccines for corona viruses and use new technologies to boot, so there's a lot more…

> New influenza vaccines (using cell lines) were approved after use in 15,000 people

The are several important differences: (1) it took 4 years of data, not 6 months of data like Pfizer, (2) using mature, well known technology.

Now, let's compare to a flu vaccine approved with an EUA after 6 months, shall we?

https://www.bmj.com/content/362/bmj.k3948

https://www.sciencemag.org/news/2015/07/why-pandemic-flu-sho...

(Both articles describe the same vaccine, pandemrix)

It caused narcolepsy, a few hundred cases of it. That's a debilitating, life changing disease; by all estimates I know, much worse than the flu it was supposed to prevent. It's not the only case (though there aren't maney - 1976 flu vaccine causing guillan-barre, dengvax worsening dengue, israeli anthrax vaccine causing harm, probably a couple more I'm unaware of; the vast majority of vaccines -- all that I'm aware of that got full approval rather than an EUA - have a 1:1,000,000 or better adverse event profile).

And it isn't even perfectly clear why. The science article says it's likely because there's a similarity between some viral protein and some brain protein -- but that's not clear that's the reason. According to the BMJ article, basically the same vaccine but with a different adjuvant caused none of the issues.

How long did it take to figure this out? Approximately one year of data.

I urge you to read the BMJ article - it eerily describes exactly what's happening now, 11 years ago - some of the names (e.g. Fauci) haven't changed; some have.

> Are you overestimating the safety testing done on other vaccines?

I don't think I am. That's why we have VAERS and a European equivalent. You might notice that a lot of the touted efficiency and safety data is coming from Israel. Well, Israel has no VAERS equivalent, hardly tracks any adverse events for this vaccine (likely on purpose), and decreed that vaccinated people are not to be PCR tested unless they show obvious COVID symptoms, whereas unvaccinated are required to have negative test from the last 48 hours for many activities -- which means the data will show it's working even if it doesn't. Israeli data is rubbish, other data is hardly available. (I currently live in Israel and track this; It's been politicised in Israel to the point that no data coming out of Israel is trustworthy)

So, regardless of safety of other vaccines, we have very little reliable data about the new guys.

> but I wonder how you've gone about assessing previous safety proofs.

By waiting enough time to get data accumulated.

You know why we ddin't have any corona virus vaccine before 2020? It's not for lack of trying. They all failed at various stages, all of which were skipped for the SARS-Cov-2 vaccines.

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