4 ms·

Here's my ELI5 attempt. Disclaimer: the immune system is very complex, even experts really don't understand it as much as we think we do. This is a very simpl

Here's my ELI5 attempt. Disclaimer: the immune system is very complex, even experts really don't understand it as much as we think we do. This is a very simplified view of the system, but I think captures a very large fraction of the story. Let's focus on three types of antibodies - the things your immune system creates in response to a foreign object in your body - for this story: 1) IgM - this is created in your mucosal membranes when you breathe in something foreign. In the context of COVID, we'd expect to find IgM antibodies in people exposed to the virus because the mucosal membranes of the respiratory systems are the first places exposed to a respiratory virus. 2) IgG3 - this is created in your blood and is the main killer of a foreign object. This is what you think of when your immune system is fighting a virus. It also drives the inflammation which is what you generally recognize as the "flu-like symptoms". 3) IgG4 - this is created in response to what we recognize as allergens. For example, if you breathe in a bunch of pollen in the spring, you may have an IgG3 response and feel terrible. Or you body may recognize that that foreign object really isn't a big deal. In this case it will create IgG4 which basically tells your body to ignore the object until it's cleared. It's kind of the opposite of IgG3: rather than ramping up inflammation to fight the object, it's ramps it down and just says "nothing to see here" so you don't waste resources fighting something harmless. What they found is that vaxxed and boosted people have a ton of IgG4 floating around and little to no IgM and IgG3. So what does that mean? Here's where people are going to get spun up because we have to create hypotheses and test them. But even stating some hypotheses will cause the political machine to get mad. 1) IgM is really good at stopping viruses early. From this we'd expect that unvaxxed people exposed to COVID to be more resistant to future infections because the first exposure will create IgM and the virus will be stopped/attenuated in the nose. I don't know the state of the research on this, but it's a hypothesis to test. 2) IgG4 is a bad thing in the context of a replicating virus. If you have IgG4, it's telling your body to ignore the virus because it's "just an allergen". That's fine for pollen which will be cleared out of your system, but it's bad for a replicating virus because it can replicate unfettered. The hypothesis to test here is if people who are more vaxxed have more (re)infections of COVID. Another thought is that the infection may never go away and flare up occasionally (long COVID?). Again, I don't know the research, we need to test these hypotheses to understand it. But it is one piece of the puzzle and a plausible explanation for this (https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v1.full.pdf https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v...) where we see a nearly linear increase in vaccine doses and COVID infection. Again, these are just hypotheses and we need to test them without getting political about the vaccine. This may also be a plausible explanation for COVID related OAS (Original Antigenic Sin) and ADE (Antibody Dependent Enhancement) that some researchers claim they see. At a minimum we can say that the more vaxxed and boosted a person is, the more "non-standard" (compared to other vaccines) their immune response is, and that's worth further investigation.

bzmrgonz 4y ago
Very thorough ELI5, thank you. I wonder how difficult/expensive it is to test for IgG4? I ask because I do routine 7 day water fast every 3 months, and in theory, the body is suppose to repair and expel foreign substances. More importantly, it is also suppose to renew the immune system. I'd like to test the amount of IgG4 in my body.
phtrivier 4y ago
Thanks for the explanation. Although, as I understand it, I do not see how it can be anything else than a worst case scenario ? When someone inevitably spins it as "they sold you vaccines that will let you catch the disease _more_ often, we told you so, subscribe to my podcast / buy my book / vote for me / etc...", what is the counterargument ? That we need more data to confirm ? That there can be other factors causing the reinfections ? At this point, I'm looking forward for someone saying "it's more complicated than that", which is not a great sign :/
- michaelrpeskin 4y ago
  There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision can be made. A purely statistical argument would show that we'd get the outcome wrong. In non-emergency cases, we have some random people that follow the right path and that message gets amplified and we find a solution. In this case, that didn't happen (or maybe I should say "hasn't yet happened"). We are seeing with the latest twitter files that some people who were more right then wrong were silenced. The bias towards a more right answer was taken away. Why were they silenced? Could be something as simple a trying to make an easy message "anything that promotes vaccine hesitancy is bad" because good people truly believed that the vaccine would get out of it and they didn't want any confusion. Back to your comment about "worst case scenario." Yes this is bad, if the vaccine (and in particular the boosters) are actually destroying the immune system, we have a problem. Typically we would have tested this for a long time to see this effect (which is not unknown in the immunology community) but for some reason "we didn't have the time" and we rushed it into millions (billions?) of people. That is bad. Can it get worse? Yes! What if the latent IgG4-enabled virus evolves in vaccinated people and we get another outbreak of a worse virus? You can probably imagine more bad scenarios. I was a co-author on a paper about significant more (1000x) pregnancy and fertility adverse events after the COVID vaccine compared to the flu vaccine. So we're talking generational effects! Anyway, not to be too doom and gloom here, but I think you're right "it's more complicated than that" and "we need more data" we just need to collect everything we can, make hypotheses, test them, and learn. That requires lots of open communication. Extra info: earlier this summer I started to put together a figure to illustrate the "entropy of ignorance" It's outdated, I've learned more since then, but this was my best understanding this summer. You can see how it's easy to have a bad decision keep compounding into more bad decisions. And they can easily happen randomly, it doesn't take nefarious reasons. https://imgur.com/YZKu3Wn https://imgur.com/YZKu3Wn

bzmrgonz 4y ago

Very thorough ELI5, thank you. I wonder how difficult/expensive it is to test for IgG4? I ask because I do routine 7 day water fast every 3 months, and in theory, the body is suppose to repair and expel foreign substances. More importantly, it is also suppose to renew the immune system. I'd like to test the amount of IgG4 in my body.

phtrivier 4y ago

Thanks for the explanation. Although, as I understand it, I do not see how it can be anything else than a worst case scenario ? When someone inevitably spins it as "they sold you vaccines that will let you catch the disease _more_ often, we told you so, subscribe to my podcast / buy my book / vote for me / etc...", what is the counterargument ? That we need more data to confirm ? That there can be other factors causing the reinfections ? At this point, I'm looking forward for someone saying "it's more complicated than that", which is not a great sign :/

michaelrpeskin 4y ago
There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision can be made. A purely statistical argument would show that we'd get the outcome wrong. In non-emergency cases, we have some random people that follow the right path and that message gets amplified and we find a solution. In this case, that didn't happen (or maybe I should say "hasn't yet happened"). We are seeing with the latest twitter files that some people who were more right then wrong were silenced. The bias towards a more right answer was taken away. Why were they silenced? Could be something as simple a trying to make an easy message "anything that promotes vaccine hesitancy is bad" because good people truly believed that the vaccine would get out of it and they didn't want any confusion. Back to your comment about "worst case scenario." Yes this is bad, if the vaccine (and in particular the boosters) are actually destroying the immune system, we have a problem. Typically we would have tested this for a long time to see this effect (which is not unknown in the immunology community) but for some reason "we didn't have the time" and we rushed it into millions (billions?) of people. That is bad. Can it get worse? Yes! What if the latent IgG4-enabled virus evolves in vaccinated people and we get another outbreak of a worse virus? You can probably imagine more bad scenarios. I was a co-author on a paper about significant more (1000x) pregnancy and fertility adverse events after the COVID vaccine compared to the flu vaccine. So we're talking generational effects! Anyway, not to be too doom and gloom here, but I think you're right "it's more complicated than that" and "we need more data" we just need to collect everything we can, make hypotheses, test them, and learn. That requires lots of open communication. Extra info: earlier this summer I started to put together a figure to illustrate the "entropy of ignorance" It's outdated, I've learned more since then, but this was my best understanding this summer. You can see how it's easy to have a bad decision keep compounding into more bad decisions. And they can easily happen randomly, it doesn't take nefarious reasons. https://imgur.com/YZKu3Wn https://imgur.com/YZKu3Wn