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Not that I claim to fully understand what I'm talking about (IANAB), but IIRC the difference is that a COVID infection specifically targets a subset of cell-types in your respiratory system -- the vaccine is in your blood and spreads all over the place, entering many types of cells and causing them to produce spike protein.
This seems like quite a different mechanism -- doesn't mean it's not safe, but it introduces a number of unknowns.
Sure, but AIUI it can only replicate in cells with ACE-2 receptors -- which is different from the mRNA vaccines, right?
Thanks for the request for clarification -- in that sentence I was referring to the action of the virus, which does indeed replicate; for the vaccine, the mechanism AIUI would be more like "hijacks the cells which it enters to produce pure, sweet spike protein" (of the Wuhan-Hu-1 variety, plus whichever variant is being targeted in the case of the bivalent boosters)
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ACE2 receptors are very widespread, though.
Are they as widespread as cells which can be hijacked by the mRNA vaccines, though? (Or infected by adenoviruses, for that matter)
I don't know, but I'm pretty sure they are different.
Which introduces unknowns.
Which is all that I'm saying.
At a glance I couldn't find anything in particular for the COVID vaccines, but the delivery system used for the mRNA vaccines are lipid nanoparticles, which have been in use for a short while, and can be targeted towards certain cells. (Some newfangled cancer vaccines, for example, use targeted lipid nanoparticles.)
So I'm not sure about whether they would be as widespread as COVID-susceptible cells, but based on the mechanism of uptake - which has nothing to do with the mRNA - it seems to be a technology that can be used for targeted cell uptake of drug/vaccine/etc.
They would probably be different cells, though, yes, though because the vaccines wouldn't replicate like viruses do, I would expect the distribution of uptake to be more local than with a COVID infection.
Not sure what you're getting at with adenoviruses, but it would probably depend on which? Most human adenoviruses would attach to CAR, which I'm pretty sure is widespread but not exactly everywhere, or CD46, which actually is everywhere.
In other words, you don't know either.
The other major spike protein delivery vector used in (Western) vaccines was a chimpanzee adenovirus. That was Astrazenica and Johnson & Johnson I believe.
Indeed, but based on how it has been used before we can make an educated guess that it was probably not all cells, and probably more likely than not a subset of cells more restrictive than “cells with ACE2 receptor”. Are we really practicing radical skepticism here?
In any case, it‘s likely to get to fewer cells and stay more local than a virus would, given that it doesn’t replicate.
And it rather should dampen your worry (at least re:vaccine vs virus) here:
Since COVID is in your blood and spreads all over the place too.
Ah, the vector-based vaccines. I didn‘t read up much on them unfortunately.
It doesn't seem that radical to want to know some basic facts about the mechanism of a novel vaccine which is proposed to be deployed to pretty much everyone. 'Educated guesses' would certainly not be my preferred decision making tool.
...
You are not reading very carefully -- the mechanism and which particular cells are infected is different. Which might be fine. Or might not. I don't know, and apparently neither do you.
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The vaccine, afaik, doesn't 'go into your blood', but mostly stays in the muscle or the lymphatic system. And anyway, that concern also applies to most other vaccines.
Understanding the effects of vaccines, and pharmaceutical products generally, depends a lot on experiments and measurement - biology is really complex and one can't be confident in anything without testing. A vaccine or pharmaceutical that, 'in theory', should work great will often not, or have significant side effects, and a lot of knowledge has been built up on testing for and avoiding them. So none of what's been written above proves covid vaccines are good - the process of creating them and testing them was much more complex, tremendous amounts of niche domain knowledge is required to create and ensure safety for a vaccine, and none of us have that - it just rebuts specific claims that they're harmful.
I mean for some value of 'mostly' -- but it's measurable all over the place:
https://web.archive.org/web/20210404123801/https://www.pmda.go.jp/drugs/2021/P20210212001/672212000_30300AMX00231_I100_1.pdf
(Japanese report is in Japanese, but the pharmokinetics tables on pgs 16-17 are in English; notable areas with high concentrations of the nanoparticles are the liver, adrenals, ovaries, and bone marrow)
Other vaccines don't cause your cells to produce viral subunits; this is the new part, which carries unknowns.
The first part is all true -- but it doesn't seem to add up to much of a rebuttal, given the novelty of the mRNA aspect.
Not sure about marrow, but COVID can infect liver, adrenals, and gonads.
In what percentage of cases?
Cursory search doesn't reveal a study that studies exactly what you want to find, that is, percentage of uptake by extrapulmonary organs/percentage of cases with uptake in such organs.
There is reasonable evidence, however, for extrapulmonary infection-related changes during COVID for patients that look suspiciously like direct infection, though, which leads to multi-organ failure in some cases (e.g. 36% of autopsied patients in this study, and multi-organ viral infection found in autopsies. This proves less - it might not be directly caused by cells infected with the virus, especially since some are just - but some of it likely is. Qualitatively, we see extrapulmonary infection via the stated mechanism - virus gets into bloodstream, ACE2 is everywhere, etc.
To quote a paper focused on hepatic COVID manifestations as an example:
Liver enzyme dysfunction is fairly nonspecific, but change in albumin and bilirubin levels indicate an impact on enzymatic activity and synthetic function of the liver. (There's also a few more interesting things in the paper, but probably out of scope here.)
You could likely find similar things for quite a few organ systems. Not perfect, mind you, and many drawing data mostly from autopsies (which would select for severe cases), but it gives you a picture of how widespread the infection goes; the GI survey, for example, finds 41% patients having fecal shedding of virus (though the study also selected for people with GI symptoms).
This is not even comparing like-to-like, given that we would be comparing estimated uptake on the one hand and metabolic dysregulation on the other, when I don't think there's been any evidence or studies on multi-organ dysregulation and/or failurepost mRNA vaccine. Purely speculating here, I would expect that COVID invasion of extrapulmonary organs that nevertheless don't result in significant dysregulation and/or organ damage in mild cases to be quite a bit higher than levels of active multi-organ disease.
It's also not including indirect effects from COVID that are nevertheless dangerous, like RAAS system dysregulation from ACE2 downregulation post infection, or cytokine storm, or clotting, or whatever weird shit it does to the vasculature. (IIRC quite a lot of the severe illness comes down to COVID impacts on the vascular system, which predictably has impacts everywhere even if it doesn't preferentially infect organ X or Y.)
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