That's pretty believable, if long covid is a long term reaction to the spike protein.
It's not like not getting the vaccine would prevent getting long covid in that case though. It does not however explain why getting the vaccine would get rid of long covid though?
Actually, it could. If long COVID is a reaction to the spike, given that infection produces multiple orders of magnitude more protein and that vaccination leads to lesser viral vaccination, it's almost certainly a net positive.
If it's because of latent infection, a vaccine that helps stop infection would reduce the amount of spike protein to zero, which would help.
If it's an autoimmune reaction, vaccines generally provide a different immune reaction than infection, and subsequent immune reaction to infection would be different, so it could improve immune reaction.
"infection produces multiple orders of magnitude more protein and that vaccination leads to lesser viral vaccination"
Do you have a source for this claim? Last time I tried to research this and get a figure for the difference, there was just no way to directly compare dosages. But it turned out that antibody titer is much higher in the vaccinated than the unvaccinated-and-infected, which implies the effect of the vaccine is stronger.
The general rule seems to be that whatever you assume about COVID vaccines, regardless of how basic it may appear to be, will turn out to be riven with conflicting facts when trying to find support for it.
Antibody titers don't imply anything about the relative effect of vaccination versus infection. You have to assay cellular immunity in order to make a meaningful comparison.
But we're not talking about vaccine effectiveness, we're talking about strength of the response provoked in the body. It would be nice if the relationship was as simple as a linear one between antibody levels and clinical outcomes, but as you point out, it's not. The question here is simply which produces more of the toxic spike proteins.
Yes, the antibody titer will be higher with vaccines no matter what, because the virus has some serious immune evasion mechanism and that the vaccine is much more immunogenic.
If you want to estimate the amount of spike produced by the vaccine, we can take the fact that we know the amount of mRNA in the Pfizer vaccine is 30mcg. The mRNA is ~4000 nucleotides long, which gives us a molar mass of 2000kg/mol. So the vaccine actually has 0.015 nanomoles of mRNA which turns out to be around 10^11 mRNA molecules.
Now we know COVID infection produces around 10^12 virions each of which has ~30 spikes, and there are certainly at least 3x more spike protein made that doesn't end up in a virion, so we have ~10^14 spikes from natural infection.
You would thus need each mRNA particle to enter a cell and be transcribed (impossible) and for each mRNA strand to produce 1000 spike proteins, which is very improbable.
So it is very likely that indeed vaccines produce much fewer s proteins than natural infection.
Well, thanks for attempting a numerical and physics based analysis. That's much more than you can find in the (public) documents submitted to regulators. I voted you up as I've been looking for some sort of calculation for a long time.
I have some questions though.
Firstly, I think your analysis would only be true for Pfizer. Moderna has a dose 3x stronger (90mcg equivalent).
Secondly, what exactly is the virus' immune evasion mechanism that the mRNA lacks? I thought it was the other way around - the mRNA is coded with pseudo-uridyl specifically to evade the immune system, but normal viral RNA doesn't use that trick. It would seem to be much more likely that the virus is detected by the immune system than the mRNA particles, specifically designed to evade it.
For a novel argument like this one some citations would really be helpful. Where did you get the number of virions per infection, exactly? Surely this number will vary wildly between patients? What's the CI on that? Where did the 3x number come from?
You say:
"for each mRNA strand to produce 1000 spike proteins, which is very improbable."
Why? From [1] we can read that each dose "consists of around 13,000 billion repetitions of the same 4284 characters". This seems like a huge number of repetitions of the spike protein sequence and this is a highly optimized sequence. They appeared to make great efforts to optimize it well beyond what nature would achieve. I'm not sure how to convert "strand" to "dose" here, but all your numbers and probabilities seem rather hypothetical.
So what we're left with is still something much simpler and easier to measure (antibody levels), which are higher for vaccines, suggesting the body perceived it as a more aggressive invasion. And that's a problem: more antibodies = higher chance of autoimmune disease, at the very least.
> Why? From [1] we can read that each dose "consists of around 13,000 billion repetitions of the same 4284 characters". This seems like a huge number of repetitions of the spike protein sequence and this is a highly optimized sequence. They appeared to make great efforts to optimize it well beyond what nature would achieve. I'm not sure how to convert "strand" to "dose" here, but all your numbers and probabilities seem rather hypothetical
Yes, each repetition is an mRNA strand, so what I wrote is in agreement with that quote. You would need each "repetition" to be translated to 1000+ spike proteins. Of course, the sequence is highly optimized, but it has to be optimized for many things - speed of translation and immunogenicity are much more important than persistence, and persistence is what would allow it to be translated many times. Least of which is because if you produce too many too fast the cell is just going to explode or form syncytiae.
> Secondly, what exactly is the virus' immune evasion mechanism that the mRNA lacks? I thought it was the other way around - the mRNA is coded with pseudo-uridyl specifically to evade the immune system, but normal viral RNA doesn't use that trick. It would seem to be much more likely that the virus is detected by the immune system than the mRNA particles, specifically designed to evade it.
Normal viral RNA is encapsulated in a virus. There is no need for pseudouridine because there won't be RNA in the open for the immune system to react until after infection. The vaccines need it because they want to create immune response to the spike instead of the mRNA and to lead to higher delivery. This, instead of leading to immune evasion, prevents the immune system from reacting to the wrong thing, which makes the vaccine more effective.
The immune evasion capability of the virus is completely different from pseudouridiliation, and are actually detrimental. It interferes with many signaling molecules necessary to the immune system, and induces the immune system to act as if it wasn't a virus but instead a parasite to some extent. This causes the immune system to react very inefficiently and erratically, causing responses that are damaging to the body, and also affects antibody formation. It can also induce T-cell exhaustion
The virus also has more proteins than simply the S protein, which means that the immune system may initially focus on other parts of the virus.
Then there is the fact that the lipid carrier as well as mRNA itself is highly immunogenic, even with pseudouridine. This means that for the same amount of spike protein, the vaccine will create a very strong and immediate immune reaction.
I went with the higher estimates because Delta (and thus Omicron) have much higher viral loads. This is on the order of 1000x, but I only took 100x more than the lowe bound to be very conservative. If you want to be accurate, you can multiply the number of spike protein from the virus that I wrote by 100x : https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8375250/
As you can see, it is normal that we would see a higher number of antibodies from the vaccine.
> more antibodies = higher chance of autoimmune disease, at the very least.
Absolutely not. What matters for autoimmune diseases isn't the amount of antibodies, but the type of antibodies. Vaccines only have one out of a dozen proteins in the vaccine and in only one conformation and one form, while the virus has all of those proteins in many conformations and will accumulate hundreds of mutations leading to even more antigens. So at the same amount of antibodies we expect a higher chance of autoantibodies from natural infection.
As for why they didn't send this to regulators, why would they? They have empirical data from trials that show this didn't happen, and the regulators didn't ask for it.
As for the 3x, viral assembly is a haphazard process. Virus proteins very often don't come together right - for some viruses the vast majority of virions are incomplete. I'm not aware of data on it for COVID except that the vast majority of virions that do have RNA (and not all do) are incomplete and can't infect, (see the number of virions paper), so for every RNA containing virion there is almost certainly much more than 3x as many spike proteins as if it was a complete virus. 3x is just a very conservative estimate.
Not all of it. A certain fraction of the lipid membranes wont ever get to a cell intact. A good fraction of mRNA will be damaged and won't be viable. Etc, etc.., the long and short of it is that much less than 100% of the RNA will actually make it to a cell.
Maybe I misread your post if your claim was that not every mRNA strand enter the cell. apologies.
That said, this type of mass analysis is deeply flawed.
It ignores the difference between mRNA weight and spike protein weight. I believe this lowers the ratio as the mRNA is more massive than the spike protein encoded.
On the other side, it ignores the number of of times each mRNA strand is transcribed to protein. It also ignores the adjuvant effect of the lipid nanoparticle, which amplifies the immunogenicity of the protein mass.
That said, I think the entire discussion of mass is a gross oversimplification to the question of comparing possible long covid autoimmune conditions between vaccination and natural infection. There is soo much more going on: rates of immune response, differences in intensity, differences in immunogen proteins, ectara.
Overall, I think it is an open question. It seems plausible that vaccination could cause long covid in some cases, especially given that it has been show capable of causing autoimmune multisystem inflammatory syndrome. It is also plausible that it could be used to address long covid, by attenuating the immune response or some other mechanism.
I'm not doing mass analysis. That's why I divided by the molar mass of the mRNA strand. I'm comparing the number of virions to the number of mRNA strands. I already corrected for what you mentioned.
> It also ignores the adjuvant effect of the lipid nanoparticle, which amplifies the immunogenicity of the protein mass.
If you think long covid is caused by the immune reaction, this is all moot, as I said in the original post. It's very possible longcovid is autoimmune, but it's possible it's not.
I saw mrna strand vs spikes, so this at least leaves out transcription cycles. I point this out now not to be argumentative, but simply because I'm curious. My understanding was that it was not one to one.
Also for the sake of curiosity, what are the non immunogenic theories? Some sort of persistent damage from the spike count?
Yes, I also took into account transcription cycles - it would take 1000+ transcriptions per mRNA strand to break even.
But yes, persistent damage from spikes is a non immunogenic theory. There are also theories of persistent infection and viral damage to various organs, as well as exhaustion of the immune system, etc..., and of course it could be a sum of any.
It's not like not getting the vaccine would prevent getting long covid in that case though. It does not however explain why getting the vaccine would get rid of long covid though?