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If this is a function of the spike protein, doesn't that mean the mRNA vaccines cause this effect as well?
The spike protein from the virus bands to ACE2 receptor, messing them up. The vaccine primes our bodies to attack the spike protein, preventing it from binding to ACE2 and thus preventing it from messing up ACE2 receptors.
But the vaccine causes the body to produce spike protein. The CDC emphasizes the spike protein is harmless, but this new research finds that the spike protein itself can cause damage. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different...
This has been the clever guy hot take for a few days now. Yet millions of people are walking around vaccinated without damage, so....
We also have 150+ million people around the world who've had the virus walking around without damage.

The point is how should we change our recommendations? Are older people or others with certain medical conditions more susceptible to damage?

I don't see how shrugging off this new information is reasonable or scientific.

Start by telling people to take more zinc.
People downvoting nutrition…I don’t get it…or maybe I do.

https://www.sciencedirect.com/science/article/pii/S240545772...

Vitamin D levels had a significant difference between the case and control groups (p = 0.008). Serum calcium and serum zinc levels also had statistically significant differences between the two groups (p < 0.001).

Or walking around damaged, and they don’t know it yet.

Didn’t it take us thousands of years to realize lead was poisonous?

It didn't. Western medicine new lead was poisonous dating back at least to the second century BCE. What changed was the belief that only acute lead exposure could cause poisoning... We came to understand the mechanisms by which chronic exposure causes buildup and poisoning over a long term.
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.
> small enough amount produced forever should be safe

does 'forever' modify 'produced' or 'should be safe'? if the former, what produces a small amount of the spike protein forever (continuing, not just a small amount one time)?

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.
It's a question hacker mindset would ask. What follows from first principles given the headline; it's not an unreasonable question, even if there is no empirical evidence the vaccines are unsafe
> this new research finds that the spike protein itself can cause damage.

Downregulation of ACE-2 causes damage, not the spike protein. The spike protein itself causes downregulation, but not enough to cause damage.

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 the spike protein unit extract ones, all involve getting some of the spike protein either made in the cells, or introduce it directly.

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 coming out in the last month) show is that the vaccine outcome (specific proteins) that were assumed to be inert and only prime the immune system against the virus, are actually active and damaging. That's a big difference -- and the question of whether it makes sense to vaccinate needs to rely on actual science, not "it's a vaccine so must be good and safe" ideology. It also depends on specific attributes (e.g. age, obesity, etc.)

There's an Israeli study showing myocarditis at a rate of 1:20,000 for the 16-30 age bracket, with 1:100,000 overall (all pfizer)[0] ; the US Army stats are 1:250,000 (for a mix of JNJ,Pfizer.Moderna) but I didn't find age distribution - and these are exceptionally lean and fit individuals, compared to the general population.[1]

That's just myocarditis ; it it related to what's described in this paper? I don't know. Are there any other issues? I don't know. And generally speaking, no one else does either. But because everyone gets vaccinated, we require exceptional proofs of safety. Or at least, did before 2020.

[0] https://www.timesofisrael.com/israel-said-probing-link-betwe...

[1] https://www.military.com/daily-news/2021/04/26/pentagon-trac...

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 to it, but I wonder how you've gone about assessing previous safety proofs.

Cell culture technology has been in use for decades around the world for many other vaccines, going back 35 years at least (e.g. rabies/polio).

Genetic/DNA vaccines are new.

> 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.

> 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.

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.

You can't run a trial if there aren't any people getting infected.

By waiting enough time to get data accumulated.

This isn't a mechanistic explanation of how you've arrived at a stronger level of comfort with earlier safety trials, unless your evaluation criteria is literally just that they took longer.

> You can't run a trial if there aren't any people getting infected.

Corona viruses have been with us for a few thousand (millions?) of years. It is estimated 25% or so of colds are caused by corona viruses. And not surprisingly, they can also cause really, really bad outcomes in the sick and elderly -- in fact, there is some speculation that before they became endemic, they were as virulent as sars-cov-2.

And there definitely have been attempts; not as focused, of course, but nevertheless over many years. The most focused attempts were at SARS-Cov-1 and MERS - and both burned out quickly - but also all failed spectacularly at the animal testing stage.

> This isn't a mechanistic explanation of how you've arrived at a stronger level of comfort with earlier safety trials, unless your evaluation criteria is literally just that they took longer.

(a) animal testing (skipped entirely in this case, which would have shown perhaps that targeting the spike protein may be an issue, and

(b) yes, more time. some signals take time to surface - do read the pandermix papers I linked to. Whatever is happening now is just too close for comfort, and I sincerely hope it will end better.

What more can you ask for, when I show you a horrible experiment from 2009, which matches in almost every possible way except we're now using now technology? With articles from science and the BMJ? Is there anything that can satisfy your request for reasonable doubt?

There were animal studies:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449230/

I was just asking to understand your reasoning, I wasn't asking you to convince me it was correct, and I'm not trying to convince you it isn't correct.

Thank you, I failed to find this one in my previous literature search.

I don't have it handy now, but for at least one SARS-Cov-1 vaccine candidate everything seemed fine, and good immediate antibody response (as in this paper), but another challenge 3 months later had an ADE response with worse outcomes than a naive infection. IIRC it was done in felines, not in primates.

Beagle don't let yourself convince so easily, you are still right, they didn't done long term studies in animals, thus its not wrong to say that they skipped long term efficacy or safety in animals. Meaning they skipped it. In who is being done the long term studies? Yes, that's what you thinking.. in humans. These should be done in animals first for years, but what have they done? They skipped it... If you read carefully the study lasted 8 weeks and 15 days only. Quote "At week 8 (4 weeks after the second vaccination), all animals were challenged with the wild virus)", then "lung sections from animals that were killed at day 14 or 15". So, only two months and 15 days max, then when the vaccine was authorized they jumped directly to humans.

While in this animal trial they only waited 4 weeks after the second vaccination and challenged, the challenge you mention that was done only 3 months later, this is a small example of a mini long term follow up. They havent done that at all.. They skipped it, just to do the follow up in.. humans, so yes humans are still being trialed with the vaccines. When the next wave comes in the winter, more than 3 months from today, 7 months ahead, in October, it will be a catastrophe caused by ADE.

Myocarditis is significantly under-diagnosed in young adults, but is believed to be on the order of 10 cases per 100,00 per year in the population.
Perhaps, I couldn't find reliable data, and apparently neither do the people doing the Israeli study (that much is stated in the copy of it that was leaked ; it's in hebrew).

However, their metric was IIRC "within 3 days of first or second dose"; so 6 days worth of myocarditis compared to your full year number, so a factor of 60 (assuming uniform distribution over the year) to put on same scale.

Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases https://www.nature.com/articles/aps201825 Supplementing zinc can reduce the risk of atherosclerosis and protect against myocardial infarction and ischemia/reperfusion injury.
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 our child (we did) especially because it's safety profile, while still good, is not as good as the MMR and polio ones.

MIS-C is a big discussion that I don't have enough time for, but according to https://www.cidrap.umn.edu/news-perspective/2021/04/new-find..., incidence in the US is 1:50,000. Acute myocarditis often goes away with no damage but not always. MIS-C does too.

And it's not even clear yet if any vaccine will stop MIS-C, so -- no, it's not an entirely acceptable risk.

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".

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.

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.

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) We let Covid spread slowly,

(c) We vaccinate.

Each scenario has associated cost. Now back to your point:

> But because everyone gets vaccinated, we require exceptional proofs of safety.

Safety is neither binary (exceptional/not exceptional) nor absolute and always relative to Covid. Each and every vaccine up to now is orders of magnitude safer than Covid for the vast majority of people (YMMV!).

Not an expert, but what's even more interesting is that among the already very few severe side effects, even fewer are due to the 'vaccine ingredients' (e.g. allergic reactions incl. blood clots) and many are conjectured to be due to the 'SARS-Cov-2 ingredients' (e.g. myocarditis). Heuristically speaking you can choose between Covid or a very very very mild version of Covid.

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 Pfizer trial. I'm not saying it should be used instead of a vaccine; but it's also not true that your list is close to exhaustive. We keep finding out new stuff. In the first 2-3 months, the intubation+ventilation regime was counterproductive; it took a while to realize, but now we know that. We also know (e.g. from Florida and Texas) that the NPI are much less effective than they were assumed to be.

> Each and every vaccine up to now is orders of magnitude safer than Covid for the vast majority of people (YMMV!).

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.

And basically, we only have short term safety data (pfizer: less than a year for 20K people, less than 6 months for the rest), so even if it is true that "every one will eventually get it", it does NOT follow that it makes sense to vaccinate everyone right now -- if it takes 20 years until "everyone eventually gets it", and severe side effects appear 2 years later, then, no, it doesn't make sense.

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. It's not just a theoretic possibility - it happened in a very similar setting just 11 years ago, and the causes are NOT perfectly understood to the point that you can guarantee it won't happen again.

> many are conjectured to be due to the 'SARS-Cov-2 ingredients' (e.g. myocarditis). Heuristically speaking you can choose between Covid or a very very very mild version of Covid.

You could be right, but that's not at all clear. This paper from Nature Immunology https://www.nature.com/articles/s41590-020-00808-x.pdf shows that 80% of unexposed people have a T-cell response to SARS-Cov-2 - that is, they have cross-immunity.

It could be that for those 80%, that response would be enough to stop the virus before it can get systemic traction, whereas the vaccine is essentially guaranteed to generate systemic effect. I asked an immunologist, who said he doesn't know the answer and does not believe anyone does without measuring.

> 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.

> 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?

> 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.

The vaccine instructs cells to produce a piece of protein from the spike. There’s no such thing as “a” spike protein, the spike is a structure of proteins that enable a lot of functions for the virus. They choose a piece of protein from the structure that’s antigenic then encode the mRNA to produce that. The mRNA is delivered into the cell by the lipid transport and the cell picks up the instruction and produces the antigenic protein fragment. Your immune system responds as expected and attacks the antigen carrying things - existing cells included. The inoculated mRNA is quickly broken down because mRNA is a standard process in cell function.

Unless the effect observed is due to the antigen the vaccine produces then you wouldn’t expect to see the same behavior in vaccinated humans as they saw experimentally with a full virus, even if some part or the full assembly of the spike is a cause for cellular damage.

From the wikipedia for Pfizer, the vaccine supposedly produces a full length spike protein [1]

https://en.wikipedia.org/wiki/Pfizer%E2%80%93BioNTech_COVID-...

No.

From that link "...two proline substitutions (K986P and V987P, designated "2P") that cause the spike to adopt a prefusion-stabilized conformation reducing the membrane fusion ability, increasing expression and stimulating neutralizing antibodies..."

It's a modified version of the spike protein designed as an antibody target, not to identically replicate the spike protein function.

Your body is non-stop taking damage every day. Its when the body can't compensate fast enough that its a problem.

The load from an mRNA vaccine is miniscule compared to severe, or moderate covid.

The vaccine causes a relatively tiny amount of spike to be produced compared with a raging infection.

A little bit of spike trains your body to identify it and neutralize it.

A whole lot of spike is toxic to your organs and damages them.

To downregulate ACE2 you need a whole lot of receptor activation and a lot of ligands floating around in your system binding to it to cause that. The dose of spike protein matters.

To downregulate ACE2 all you need is a bad enough zinc deficiency.
No idea why this is being downvoted. This is exactly what happens. But the virus destroys ACE2 (not the "reception because there is no ACE2 receptor. ACE2 is an enzyme).
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

[adndm] keep in mind the virus replicates, inside you, the vaccine doesnt, and the vaccine stays where you put it, it doesnt spread out everywhere that has a receptor

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.

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.
This is a legitimate question, so I don't know why it's being downvoted. Especially given the statement in the abstract of the paper that says, "We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo...."

That being said, other people on this thread have provided reasonable mechanistic explanations as to why the vaccines would not have this effect, but I will also add we have _empirical_ evidence that the vaccine does not impair endothelial function (or at least it is extremely rare) because we have millions of people who have received the vaccine without impaired endothelial function.

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.

Constantly. Her list of banned medications is huge. Each time she’s prescribed a medication, she has to decide if the “rare side effects” are worth risking or are worse than going untreated.
Just sayin’

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793296/

The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.

Quite strange. I've had almost the exact same skin-level reactions, only I received the BioNTech/Pfizer vaccine.
I had a red area after the second shot on my shoulder, and so did my family members including cousins in other states.
Someone I work with (female, 25 years old) had inflammation on her knuckles that is similar to what you describe. This was after her second shot - not sure if it was Moderna or Pfizer, but it was MRNA. She's fine and it eventually went away, but it's certainly interesting. She doesn't have any autoimmune disorders that she knows of.
The vaccine appeared to piss off the RSI in my right arm for about two weeks. I would have gotten the shot in my left arm if I knew that was going to happen.
I've also not seen any studies about side effects in people who already had the virus before getting the first dose.
Disclaimer: I am not qualified to interpret this study and have no experience in this field.

So the study indicates that the Spike Protein binds to ACE2 that is found in the membranes of cells located in the lungs, arteries, heart, kidney, and intestines, and down regulates them to the point where it damages your mitochondria in those organs. So according to the research they did, it's not just the virus that can hurt you but the mechanism (Spike Protein) the virus uses to attach to your cells and replicate that can cause this damage.

It is likely that the vaccine itself which holds the mRNA and not the actual Spike Protein or Virus (just the instructions on how to make the Spike Protein) is administered in a intramuscular area of the body (Shoulder Area), never able to live long enough (mRNA dies off quickly) to enter these areas where ACE2 is found (Heart, Lungs, Kidneys, etc). The muscle tissue/cells in the upper arm create some Spike Protein and your immune system basically say WTF is that and kills it long before it can ever reach these organs or areas of the body.

The real Virus typically enters the body through the nose and mouth and heads directly into the sinuses and can spread very quickly to lungs and then move on from there into other organs. If you're someone who is one of the folks (Metabolic Disease, severe autoimmune dysfunction) who might be susceptible to what this study suggests, the vaccine is the way to go since it might give you a better chance to avoid the negative outcome from the Spike Protein affecting ACE2 and then damaging the mitochondria in your Organs cells.

>is administered in a intramuscular area of the body (Shoulder Area), never able to live long enough (mRNA dies off quickly) to enter these areas where ACE2 is found (Heart, Lungs, Kidneys, etc)

We know to where it typically tends to go now, "the muscle tissue at the site of injection, the lymphatic tissue downstream in your armpit on that side, your spleen, and (for the first day or two) your liver. " [0]

[0]https://blogs.sciencemag.org/pipeline/archives/2021/01/21/mr...

The funny thing is that list of places the mRNA gets to does not have any overlap with my list of "places in my body where I want SARS-CoV-2 spike protein".
A good question, one of the paper's authors had the following responses on Twitter:

https://twitter.com/manorlaboratory/status/13887170085444198... https://twitter.com/manorlaboratory/status/13887291512893153...

First tweet:

    i’m going to give a full response asap. but quickly for the record:
    1) the (relatively) small amount of spike protein produced by the mRNA vaccine would not be nearly enough to do any damage
    2) i happily got the mRNA vaccine, FWIW
    3) i encourage everyone to get it
Second tweet:

    a couple prelim responses to anti-vaxxers misrepresenting these findings (here: https://twitter.com/manorlaboratory/status/1388717008544419843?s=21). tl;dr: mRNA vaccine is waaaaay safer than COVID19 and everyone should get it - I did and everyone in my family did as well! Our paper just shows this disease really sucks.
Just this morning I was reading this paper [1] which is looking at the effects of the spike protein alone on pulmonary function - it’s a pretty straightforward read once you get beyond the acronyms:

https://www.mdpi.com/2076-393X/9/1/36/htm

Probably but it's not like they can increase exponentially in number. It's as much about the viral load as the viral type. It's not an on or off switch.
"Endotheliitis is an immune response within the endothelium in blood vessels, in which they become inflamed. The condition can cause oedema of the surrounding tissue, including the stroma, and can cause irritation and pain. If it is within the cornea, it can result in permanent loss of vision. The condition can be caused by a number of factors, such as mumps and cytomegalovirus under certain circumstances." (Wikipedia)

And, as to the first question that came to my mind, from the paper: "Collectively, our results suggest that the S protein-exerted EC damage overrides the decreased virus infectivity. This conclusion suggests that vaccination-generated antibody and/or exogenous antibody against S protein not only protects the host from SARS-CoV-2 infectivity but also inhibits S protein-imposed endothelial injury and ultimately decrease cardiovascular complication-associated mortality in COVID-19 patients."

(comment deleted)
My blood vessels get inflamed now and then. In Sjogrens world it’s known as a “flare”

It’s horrifically painful. There is no sympathy from anyone since you look normal.

You have our sympathy, I think there are enough of us here which known that looking fine doesn't mean being fine.
I had a friend with that. The flares could have her basically out of action for a month or more as she was IT and found it impossible to work during those times.
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 are compromised there is enhanced vascular permeability, increased lung edema, neutrophil accumulation, and worsened lung function. In essence, once the virus begins attaching to ACE-2, ACE-2 function begins to be destroyed. ACE-2 function also tends to be less dynamic as people grow older, hence the more negative the effects of SARS infection on the elderly. [...] ACE (in contrast with ACE-2) inhibitors increase the presence of ACE-2 and help protect the lungs from injury."

Yes, that's why they went looking to verify that hypothesis and lay out the mechanism that the virus acts...
Is this Amazon book on herbal effects real? I am pretty familiar with Chinese traditional medicine, but their effectiveness is very dubious.

The author does not look like a medical professional either.

It’s unscientific nonsense, don’t waste your time.
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?
Nicotine upregulates ACE2 expression, but I don't know about women.
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.
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.
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

When I was hospitalized for covid, they were giving me zinc (among other things) every day.
Zinc supplements are part of the recommended prevention and treatment protocol. There is some research to indicate that Quercetin facilities zinc uptake.

https://covid19criticalcare.com/covid-19-protocols/i-mask-pl...

Yeah yeah yeah, but why isn’t this been blasted with the public airwaves, especially in India?

Plus, they’re giving zinc to people already sick. Why not check people for zinc deficiency and supply them with the zinc they need? I know why, it’s because we don’t believe in preventative care in this country.

Yes it is disappointing how public health authorities have focused almost entirely on exposure prevention. There should be equal focus on harm reduction for people who do get exposed.
The frustrating part is we know that some people are fine catching SARS2 and others die, yet the never want to compare the biology of these people. We have the largest data set ever of something that could lead to the prevention of illness yet they just want to treat everyone the same.
Proponents of hydroxychloroquine have been saying that it needs to be taken with zinc to be effective.