5 ms·

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

by 8note 5y ago

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?

sudosysgen 5y ago
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.
- native_samples 5y ago
  "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.
  - sudosysgen 5y ago
    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.
    - native_samples 5y ago
      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. [1] https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
      - sudosysgen 5y ago
        > 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. See: (https://www.frontiersin.org/articles/10.3389/fcell.2021.789427/full https://www.frontiersin.org/articles/10.3389/fcell.2021.7894...) 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. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ The source for the number of virions is : https://www.pnas.org/content/118/25/e2024815118 https://www.pnas.org/content/118/25/e2024815118 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/ 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. I hope you will appreciate this response!
  - nradov 5y ago
    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. https://peterattiamd.com/covid-19-current-state-omicron/ https://peterattiamd.com/covid-19-current-state-omicron/
    - native_samples 5y ago
      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.

by 8note 5y ago

sudosysgen 5y ago

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.

native_samples 5y ago
"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.
- sudosysgen 5y ago
  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.
  - native_samples 5y ago
    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. [1] https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/ https://berthub.eu/articles/posts/reverse-engineering-source...
    - sudosysgen 5y ago
      > 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. See: (https://www.frontiersin.org/articles/10.3389/fcell.2021.789427/full https://www.frontiersin.org/articles/10.3389/fcell.2021.7894...) 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. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8457632/ The source for the number of virions is : https://www.pnas.org/content/118/25/e2024815118 https://www.pnas.org/content/118/25/e2024815118 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/ 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. I hope you will appreciate this response!
- nradov 5y ago
  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. https://peterattiamd.com/covid-19-current-state-omicron/ https://peterattiamd.com/covid-19-current-state-omicron/
  - native_samples 5y ago
    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.