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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

#61

Post by karaterobot »

tmabraham wrote: post #56
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?

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.

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

#62

Post by beagle3 »

maxerickson wrote: post #58
beagle3 wrote: post #57

Earlier quoted context omitted.

> 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…

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.

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

#63

Post by lamontcg »

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 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.

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

#64

Post by jm4 »

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

When I was hospitalized for covid, they were giving me zinc (among other things) every day.

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

#65

Post by podgaj »

jm4 wrote: post #64
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

When I was hospitalized for covid, they were giving me zinc (among other things) every day.

Yes, I’ve already known about that. I’m just wondering why they’re not checking peoples zinc levels or why they’re not recommending people supplement with zinc.

The rate of zinc deficiency in India is near 50%!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702335/

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

#66

Post by podgaj »

ronri19 wrote: post #12
gameswithgo wrote: post #10

Earlier quoted context omitted.

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.

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

#67

Post by podgaj »

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.

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.

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

#68

Post by dathinab »

treeman79 wrote: post #40
morsch wrote: post #4

"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." (Wikipedi…

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.

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

#69

Post by IAmGraydon »

dcow wrote: post #26
busyant wrote: post #17

Earlier quoted context omitted.

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 ha…

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.

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.

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

#70

Post by Pyramus »

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…

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.

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