This paper from 2021 raises the issue that Abs against Spike protein are cross reactive with antigens from many different human tissue types. And the modRNA Gene Therapy treatment causes your body to generate large amounts of Spike protein for 200+ days in some people.
Perhaps the increase in IgG4 Abs will offset that?
"We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. ..."
I used to keep track of his feed for such good finds as this. So, it tracks with my model in the TASD series, kids start converting in the months after dose 2 just like adults, but the big question is what happens as they live with IgG4 for years and years of encounters with the virus.
I know a guy who lives on the east coast who is (was) in exceptional shape. He is 65 years old, but has lived on health food forever and this past summer bicycled across the country. He is religious and so his stress level is not terrible. He is never sick. He has had all of the covid shots and all of the boosters. He has never caught covid; he wears an N95.
About ten days ago he started to feel terrible; it was like nothing he had felt before. He developed a bad cough, a bronchial infection, and red and oozing eyes. His tests (flu, covid, RSV) came back negative; he just had a high white blood cell count. His GP put him on Amoxicillin Clavulanate and his eye doctor put him on eye drops. However, his eye doctor said that he had never seen an eye infection like his before, so he was going to consult with his colleagues. It's was at an academic hospital so it was creepy that it was something new to this doctor.
After consultation, the eye doctor decided that my friend has "adult Haemophilus influenza". I was really surprised since I did assume he had finally caught covid but wasn't testing positive for it.
I don't think this guy should be catching this kind of ailment. It is not common; it is typically found in children and the immunocompromised. I wonder if his countless covid vaccines and boosters were a factor.
If it may interest you, I came across this preprint. I'm not sure if you have seen it yet but it looked at repeat doses of Novavax's spike-based vaccine and the results seem to suggest less IgG4 conversion compared to mRNA vaccines even after 4 doses of Novavax. The big caveat is that this study carries a huge sticker of "funded by Novavax", but it seems like one of the only comparative pieces of work out there to compare the mRNA formulations with the other available ones.
This is a different topic, and I apologize for that, but you and Rintrah are the only people who seem to think about these things, at least in public. I keep reading that each case of covid makes a person more susceptible to long covid. But if the problem is reservoirs, why should that be? If you have a reservoir, you have a reservoir; why would adding to it matter? Unless the antibodies from one of the infections affects the action of the antibodies from one of the other infections. But if you have a reservoir for long enough, the virus will mutate in the reservoir, and you will get that same effect just from one infection.
I wonder if the "more covid infections are worse" effect is just a matter of the passage of time; that people who have more covid infections have just had more time pass since their first infection; I don't know if they take that into account.
Maybe it is just that each covid infection causes more direct physical damage, and long covid has nothing to do with reservoirs. But the effect of multiple infections does seem to be independent of how bad the acute phase was.
I would say probably Long Covid doesn't actually become more frequent with reinfection. 1) If a study finds that "Long Covid" rates are cumulatively higher after more infections, that doesn't mean that reinfections caused more new incidences. It could just mean ".5/per was added to 1.5/per and that made 2/per - so as a group the previously not affected were all infected again and a smaller number of new people was infected. 2) If the definition of "Long Covid" is just having some new health condition in the record, that would be as much as about acute infection severity as Long Covid after mild infections.
So, say 100 people caught covid and 10 percent ended up with long covid. And then later the 90 caught covid, and 9 ended up with long covid. And then later the 81 caught covid and 8.1 ended up with long covid. So the prior infection a person had does not predispose him/her to long covid, but the population numbers keep going up. And if you look at the group as a whole, the more infections, the more long covid.
Several months after an acquaintance of mine caught and recovered from covid, he told me that he was looking forward to a gathering because he desperately wanted to breath in the same air as other people. He was the last sort of guy you would expect to say such a thing (elderly Wisconsin religious person). That reminded me of how anesthesiologists become addicts; they breath in the air their sedated patients exhale, and it primes them for addiction. I think that people who have had covid are showing the equivalent of drug seeking behavior, by actively seeking infection; the virus was shown early on to have an analgesic effect, and I saw a study that said that it affected opioid receptors. I have also read accounts of people who claimed that catching covid made their long covid symptoms better (perhaps due to reducing pain).
It is the kind of thing that I feel is frequently written in older fiction - a chronically sick person becomes well for some paradoxical reason. But who knows whether that was based on real-life observations.
I don't think that catching covid actually cured the person's long covid. I'm guessing that they felt better for a while due to the analgesic effect of the most recent infection, and then later on felt worse than ever. You never see any follow ups to the "I'm cured, hallelujah" posts.
I've read that catching measles can wipe out existing immune memory. So maybe multi vaccinated people who are infected by measles will get a reset? But they were mostly vaccinated for measles as children, so can't catch measles. But if their immune systems are shot due to multiple covid infections, then they can catch measles anyway, and can get a reset?
Right, measles declutters the B Cell repertoire, so maybe it is good for removing harmful B Cells (auto-immunity, and here, mRNA-trained IgG4-converters). And it is maybe also good for killing tumors. But there's no good way to target it or solve the paradox of post-exposure immunity (measles therapy for cancer was the topic of a few papers in the 00s but it never went anywhere).
Interesting post Brian. It will be fascinating to see how this situation develops.
I’m trying to tie up the data you have presented, here and previously, with anecdotal outcomes of recent infections from my peer group.
Of 3 couples infected/exposed this winter (35 yr olds in the uk, all 3 dose pzifer, all suspected first infection after their 3rd dose in 2022 - so theoretically ig4 converters)
- Couple 1
- quote ‘was literally coughing up bits of lung’
- Partner had week long infection
Couple 2 and couple 3
- 1 had mild 5 day infection
- Partner not infected
This ‘sample’, assuming that infection history of 3 doses before first infection is an accurate case history, has got me pondering: Are there other factors that could contribute to severity of infection (or susceptibility to infection) for vaccinees with ig4 conversion? I’m wondering about the effect of innate immunity for example.
Or put another way, would we be able to accurately predict severity of infection for an individual if we measure a groups’ ig4 levels, or are there many other confounders?
I think a big confounder would be the person's general metabolic health. It was fairly well established that early on in the pandemic the metabolically compromised people were the ones who suffered more severe Covid: the overweight, the diabetic, etc.
I have a whole big series from last year. If there is a harm I think it is most likely persistent infections, and this manifests as either more Long Covid or sporadic post-infection organ failure. Because at a certain point if infected cells aren't killed and a little bit of virus keeps surviving then T Cells are going to tap out as well, and the body will just want to "live with the virus." So sort of like how chronic Hepatitis goes except with any organ anywhere. https://unglossed.substack.com/p/tolerance-and-severe-disease-pt-3
Another person writing about the IgG4 class switch:
https://veryvirology.substack.com/p/igg4-antibody-class-switch-end-of
This paper from 2021 raises the issue that Abs against Spike protein are cross reactive with antigens from many different human tissue types. And the modRNA Gene Therapy treatment causes your body to generate large amounts of Spike protein for 200+ days in some people.
Perhaps the increase in IgG4 Abs will offset that?
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.617089/full
"We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. ..."
A video on IgG4 in todlers (who does that to their children?).
He seems to hint that the authors avoid answering certain questions and hope their paper will shut people up:
https://www.youtube.com/watch?v=L7mxQ_FtXp0
I used to keep track of his feed for such good finds as this. So, it tracks with my model in the TASD series, kids start converting in the months after dose 2 just like adults, but the big question is what happens as they live with IgG4 for years and years of encounters with the virus.
I know a guy who lives on the east coast who is (was) in exceptional shape. He is 65 years old, but has lived on health food forever and this past summer bicycled across the country. He is religious and so his stress level is not terrible. He is never sick. He has had all of the covid shots and all of the boosters. He has never caught covid; he wears an N95.
About ten days ago he started to feel terrible; it was like nothing he had felt before. He developed a bad cough, a bronchial infection, and red and oozing eyes. His tests (flu, covid, RSV) came back negative; he just had a high white blood cell count. His GP put him on Amoxicillin Clavulanate and his eye doctor put him on eye drops. However, his eye doctor said that he had never seen an eye infection like his before, so he was going to consult with his colleagues. It's was at an academic hospital so it was creepy that it was something new to this doctor.
After consultation, the eye doctor decided that my friend has "adult Haemophilus influenza". I was really surprised since I did assume he had finally caught covid but wasn't testing positive for it.
I don't think this guy should be catching this kind of ailment. It is not common; it is typically found in children and the immunocompromised. I wonder if his countless covid vaccines and boosters were a factor.
Someone else's writing on IgG4 ... needs a subscription for the whole article:
https://veryvirology.substack.com/p/igg4-antibody-class-switch-end-of
Well, it's from last January, weird that I've never seen it or that entire substack before though...
If it may interest you, I came across this preprint. I'm not sure if you have seen it yet but it looked at repeat doses of Novavax's spike-based vaccine and the results seem to suggest less IgG4 conversion compared to mRNA vaccines even after 4 doses of Novavax. The big caveat is that this study carries a huge sticker of "funded by Novavax", but it seems like one of the only comparative pieces of work out there to compare the mRNA formulations with the other available ones.
https://www.medrxiv.org/content/10.1101/2024.01.17.24301374v1
Yes - Igor reviewed it, and it’s used for my combined results here (source 3, just for the pre-nv levels)
This is a different topic, and I apologize for that, but you and Rintrah are the only people who seem to think about these things, at least in public. I keep reading that each case of covid makes a person more susceptible to long covid. But if the problem is reservoirs, why should that be? If you have a reservoir, you have a reservoir; why would adding to it matter? Unless the antibodies from one of the infections affects the action of the antibodies from one of the other infections. But if you have a reservoir for long enough, the virus will mutate in the reservoir, and you will get that same effect just from one infection.
I wonder if the "more covid infections are worse" effect is just a matter of the passage of time; that people who have more covid infections have just had more time pass since their first infection; I don't know if they take that into account.
Maybe it is just that each covid infection causes more direct physical damage, and long covid has nothing to do with reservoirs. But the effect of multiple infections does seem to be independent of how bad the acute phase was.
I would say probably Long Covid doesn't actually become more frequent with reinfection. 1) If a study finds that "Long Covid" rates are cumulatively higher after more infections, that doesn't mean that reinfections caused more new incidences. It could just mean ".5/per was added to 1.5/per and that made 2/per - so as a group the previously not affected were all infected again and a smaller number of new people was infected. 2) If the definition of "Long Covid" is just having some new health condition in the record, that would be as much as about acute infection severity as Long Covid after mild infections.
But mostly it seems like 1 is what is true. e.g. https://www.medrxiv.org/content/10.1101/2023.01.03.22284042v1 Fig 3 lower risk of diagnosis after reinfection except for first wave Omicron (a lot of kooky demographic variables would have been at play there) https://www.jpeds.com/article/S0022-3476(23)00311-6/fulltext same rates of long term symptoms in kids. So mostly the 'more risk in reinfection' trope is just misinterpreting the numbers.
Thank you.
So, say 100 people caught covid and 10 percent ended up with long covid. And then later the 90 caught covid, and 9 ended up with long covid. And then later the 81 caught covid and 8.1 ended up with long covid. So the prior infection a person had does not predispose him/her to long covid, but the population numbers keep going up. And if you look at the group as a whole, the more infections, the more long covid.
Several months after an acquaintance of mine caught and recovered from covid, he told me that he was looking forward to a gathering because he desperately wanted to breath in the same air as other people. He was the last sort of guy you would expect to say such a thing (elderly Wisconsin religious person). That reminded me of how anesthesiologists become addicts; they breath in the air their sedated patients exhale, and it primes them for addiction. I think that people who have had covid are showing the equivalent of drug seeking behavior, by actively seeking infection; the virus was shown early on to have an analgesic effect, and I saw a study that said that it affected opioid receptors. I have also read accounts of people who claimed that catching covid made their long covid symptoms better (perhaps due to reducing pain).
It is the kind of thing that I feel is frequently written in older fiction - a chronically sick person becomes well for some paradoxical reason. But who knows whether that was based on real-life observations.
I don't think that catching covid actually cured the person's long covid. I'm guessing that they felt better for a while due to the analgesic effect of the most recent infection, and then later on felt worse than ever. You never see any follow ups to the "I'm cured, hallelujah" posts.
I've read that catching measles can wipe out existing immune memory. So maybe multi vaccinated people who are infected by measles will get a reset? But they were mostly vaccinated for measles as children, so can't catch measles. But if their immune systems are shot due to multiple covid infections, then they can catch measles anyway, and can get a reset?
Right, measles declutters the B Cell repertoire, so maybe it is good for removing harmful B Cells (auto-immunity, and here, mRNA-trained IgG4-converters). And it is maybe also good for killing tumors. But there's no good way to target it or solve the paradox of post-exposure immunity (measles therapy for cancer was the topic of a few papers in the 00s but it never went anywhere).
Interesting post Brian. It will be fascinating to see how this situation develops.
I’m trying to tie up the data you have presented, here and previously, with anecdotal outcomes of recent infections from my peer group.
Of 3 couples infected/exposed this winter (35 yr olds in the uk, all 3 dose pzifer, all suspected first infection after their 3rd dose in 2022 - so theoretically ig4 converters)
- Couple 1
- quote ‘was literally coughing up bits of lung’
- Partner had week long infection
Couple 2 and couple 3
- 1 had mild 5 day infection
- Partner not infected
This ‘sample’, assuming that infection history of 3 doses before first infection is an accurate case history, has got me pondering: Are there other factors that could contribute to severity of infection (or susceptibility to infection) for vaccinees with ig4 conversion? I’m wondering about the effect of innate immunity for example.
Or put another way, would we be able to accurately predict severity of infection for an individual if we measure a groups’ ig4 levels, or are there many other confounders?
I think a big confounder would be the person's general metabolic health. It was fairly well established that early on in the pandemic the metabolically compromised people were the ones who suffered more severe Covid: the overweight, the diabetic, etc.
I have a whole big series from last year. If there is a harm I think it is most likely persistent infections, and this manifests as either more Long Covid or sporadic post-infection organ failure. Because at a certain point if infected cells aren't killed and a little bit of virus keeps surviving then T Cells are going to tap out as well, and the body will just want to "live with the virus." So sort of like how chronic Hepatitis goes except with any organ anywhere. https://unglossed.substack.com/p/tolerance-and-severe-disease-pt-3
Okay good, it's not a sure sign of terrible things for transfected people (which happens to be most everyone I love).