BTW I know you or your friends will write back w/ all the real world data that supposedly proves your case, but I think you're missing my point. If your story is that an elephant walked through a crowded room, then I would expect that EVERYONE would have noticed - you wouldn't have trouble rounding up witnesses to an elephant walking through the room. And that's my point: the evidence for the safety and efficacy of a vaccine that BILLIONS of people took should be impossible to miss; the fact that this evidence isn't obvious is the problem. I should be struggling to find ANY unvaxx'd population that's doing better than the vaxxed, not the other way around. So I'm not arguing the particulars of your evidence; rather, I'm arguing a larger point: the evidence isn't what we'd expect, and that's a problem.
Look, if you told me an elephant walked through a crowded room, the fact that you could find a FEW witnesses who saw the elephant wouldn't reassure me at all. If 3 or 4 out of 100 potential witnesses saw that elephant, I'd doubt those witnesses - I wouldn't assume that they were more perceptive.
To illustrate my point by analogy, if I developed a safe & effective vaccine for cancer, you wouldn't be struggling to explain why cancer deaths hadn't dropped, nor would you struggle to explain why deaths hadn't fallen. Granted, COVID's never been as dangerous as cancer, so I admit some of it is that we were lied to about COVID in the first place, but the idea that we've been lied to isn't particularly reassuring now is it? I mean if they lied to us about COVID why should I trust them about the vaccines?
The problem here is that you're telling me an elephant walked through a crowded room and only 3 or 4 people noticed because you know elephants - it's hard to notice when they walk through crowded rooms. Your story doesn't make sense. What should be clear and obvious is obscure...WHY?
It's interesting how you devote so much of your time to insulting your opposition; they don't do anything like that at all (in fact, they speak respectfully of you & link to your cite). In your experience, does the guy who's hurling all the insults have the better of the argument?
More importantly, I'm interested in the structure of the argument. If vaccines are safe and effective, then why do you have to go to such lengths to prove it? Shouldn't you simply be able to say, "Here's the COVID death rate and overall death rate in vaccinated populations and here's the COVID death rate and overall death rate in unvaccinated populations; now, it's not true that the former always beats the latter, but the trend's clear - it's not a correlation of 1, but it's awfully close"?
Instead, it's all sorts of excuses about why the expected correlation can't be found. (You didn't know that Israel is just a much healthier place to live? You do now!)
Again, is that the hallmark of the truth? Is your struggle to find POPULATION level data that proves your claims just something we should ignore? Should we fail to notice that you have to speculate over and over again as to why the POPULATION data doesn't fit your theory? You can tell me all the problems w/ the various studies; you can point to studies that "prove" your point, but you can't point to any real-world population level data (because that's messy or filled w/ confounding variables or whatever).
Sure, your story is possible, but is it truly plausible?
The unvaccinated aren't dead. Or dying. The vaccinated aren't living. Or healthy. At least, there's no discernible trend on each side's health. It's impossible to id a high vax or low vax population merely from their COVID deaths or overall death. If anything, low vax = better health as the African countries have great COVID #'s and low vax rates. (Again, not claiming this proves vax is bad; just saying that there's a disturbing lack of evidence for your side where there should be evidence for your side.)
Do see the problem? It takes - according to you - an extraordinary amount of expertise to see the benefits of vaccination, which doesn't make any sense. Your side should be obvious; my side should be struggling to find real-world proof.
Long and short, why are you struggling to explain the UK? Shouldn't that be obvious? (Like the general trend (which favors the vax) isn't seen here because everybody knows tea kills and they love tea or some other UK specific explanation).
I mean from my perspective your entire analysis fails the obvious counter: the UK keeps better stats and has publicized them more. Since there's every reason to believe Israel either doesn't know (worse stats) or lies (same stats but less transparency), why isn't THAT the explanation? The fact that you don't even mention the stats issue but talk about Israel's climate instead tells me that you were driving to support a specific conclusion.
To me, this is sort of a who are you going to believe - your lying eyes or me, the expert - situation. The real world should confirm your theories; it doesn't, so you keep trying to "explain" why the real world isn't as reliable as your theories. I have a problem w/ elevating theories and lab results above the real world.
Even if true, the author appears to have misplaced the caveat "for this specific virus". Sneaky sneaky!
"a new pathogen with more than 30 mutations on the S protein evoked NO new immune response"
I read somewhere (I think it was up to Delta variant) that the T-cell epitopes had not changed at all. Cannot find that page / study now, but searching for omicron t-cell epitopes turns up
T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant
where they observe, " In the Omicron variant, 80.4% (74/92) and 94.7% (178/188) of epitopes from the spike and nonspike proteins, respectively, were fully conserved, and 90.0% (252/280) of CD4+ T cell epitopes were completely conserved. These results indicate that the majority of T cell epitopes are considerably conserved in the Omicron variant."
Mentioning "30 mutations on the S protein" is all well and good but if said mutations do not change the epitopes the infected / phagocytic cells present to T cells via MHC then it's pretty much irrelevant.
My understanding is, B cells most reliably respond to **new** threats via T-cell co-stimulus. If T-cell stimulus remains largely unchanged (because the epitopes are pretty much the same), then to my way of thinking, "NO new immune response" is exactly what you'd expect.
I didn't meant to imply that the author was in full-blown VIAIDS territory, just that "ceased to be trainable in the context of this virus" is already absurd to claim based on... 8 monkeys that demonstrate the opposite of the claim anyway. Maybe I'll add a disclaimer so that I don't appear to be strawmanning.
Skipping to your last graph - and likewise, that is what would be expected if so-so antibodies reduce immune stimulation. IRL, the term for this is "immunity." But in IRL IRL, the immune system is not centralized so there's never any "one" response. Both antibodies and T Cells are leaky barriers, so there's a permissiveness, as well as a paper rock scissors interplay once you throw in innate immunity with the fascinating result that memory immunity takes a "back seat" after antibodies fade (antibodies (expire)-> innate immunity (if fail)-> resident t cells (if fail)-> ramped up antibodies and new gc-trained immune response) but the implications of this are not generalizable (since every pathogen is different) beyond the statement that "it allows for a lot of different dynamics."
Of course, (variant) vaccination circumvents the middle two stages, and more promptly activates the first part of the fourth stage, reducing the activation of the second part. However, even this is not generalizable. The omicron-boosted macaques defied OAS by not re-upping their WA1 response as much as the 1273-boosted.
Ironically, it feels like many people who have clung to OAS have themselves become a one trick pony. I think we need to come to terms that Substack operates no differently than any other forms of media such as YouTube or Twitter, and because of that people have typecasted themselves to continue to cover topics that they believe provide them with a lot of attention. It's likely why OAS has sprouted up all over the place as a justification for what's happening with these vaccines, mostly because it may provide them some position in the dissenting COVID narrative. I think because of this they may not be able to let it go instead of examining studies and taking a more cautionary approach.
Indeed - that was the theme of my Groundhog Day allusion! Besides the social media engagement-chasing aspect, both of the authors I have taken aim at here pass notes with each other and so there's a groupthink aspect. And just like both could probably read one sentence I write and tell I don't understand statistics / whatever it is that the other one does, it is obvious that neither reads much immunology research.
I will admit that immunology is so far above me that I generally struggle with much of these antibody and vaccine studies, so I do appreciate your ability to look into the methodology and raise pertinent questions. It's really the methodology that provides evidence as to the generality of the study.
And if you're wondering why I'm responding 3 months later, it's because I've been looking into OAS again to reexamine a few points. Although my position hasn't changed I'm seeing OAS pop up in the mainstream in regards to these new Omicron subvariants. What an interesting turn of events, even though I don't find the evidence to be all that convincing in favor of OAS.
I think I've been noticing the same thing, but I am barely keeping track of my own reading. I'm aware Mobeen highlighted another totally statistically fabricated prior-coronavirus-imprinting study from this winter, but at least seems to stay on topic RE "perpetual variant vaccines" which is the only context in which prior immunity can be portrayed as a "negative."
"Bartram" highlighted https://www.science.org/doi/10.1126/science.abq1841 which is just a load of nonsense - no unvaccinated Omicron infected set to actually compare with, yet tons of impossible to even parse conclusions about the effect of vaccination. *edit: Ok I was too hard on the paper, in that it isn't trying to make too much of its own results; it's still weird that the unvaxxed HCWs weren't compared in general and that Fig S5B doesn't compare the Wuhan+Omicron response to even a single other type of +Omicron response.
It's infuriatingly stupid on a really fundamental level. Like just a basic inability to be logical and persistent intentional lack of precision in language in all the OAS lit (except for maybe Yewdell's review). Just to get something published.
Boy that's a chunky paper, and so is the supplemental material (which I usually miss!). I am finding it hard to figure out some of these issues. It only came up because I wrote a post on the widely cited chicken study and a few commenters were discussing OAS.
Then I went scouring a bit and didn't realize the level of "immune imprinting" papers that have been released. Aside from the nonsensical inclusion of the N protein in the analysis of OAS, I find it strange that pro-OAS people haven't addressed the role of seasonal colds in OAS. I mean most of us here are adults so it's far more likely that we came across the common cold before COVID. At the time that we are blaming continuous vaccinations why is no one blaming the cold they got when they were 3 years old on imprinting those spike antibodies?
But like I said, your analysis of these immunological papers far exceed my own so I just decided to go digging into your old posts to see if there was something I was missing.
I also like your point that MDV seemed to already be gaining virulence spontaneously. And history is full of such spontaneous changes in "virulence" (as measured by the constantly changing instrument of the host species's health). Hopefully I'll be getting back into that kind of evolutionary / immune equilibrium theorizing soon.
Ah, I'll take a look at that paper! I'm writing one on reinfections, and I'm ashamed to say I think a bit of immunological trickery may have been afoot with the messaging about immunity. I blame a lot of this on the use of "novelty" in describing this virus and for us believing that a natural infection would lead to permanent immunity when respiratory infections have never done so.
Yeah the MDV part was mentioned directly in the study. I don't find it reasonable to argue that vaccines may have been the cause when the authors mentioned that lymphomas were emerging almost 2 decades before they initiated any chicken vaccination campaign. But to steelman the authors, they do argue that the imperfect vaccination may not have drive the virulence, but may have helped maintain it by increasing the survivability of the infected chickens.
I love how you get annoyed on things I would not even notice. I keep coming reading you because I really don't know what your position will be on anything until I read your position.
Haha, well I'm pretty predictable on the OAS subject. On other stuff I am sure I appear wildly ambivalent - but mostly I'm just trying to not pretend the replication crisis suddenly isn't still ongoing...
Excellent read Chris… well done!
BTW I know you or your friends will write back w/ all the real world data that supposedly proves your case, but I think you're missing my point. If your story is that an elephant walked through a crowded room, then I would expect that EVERYONE would have noticed - you wouldn't have trouble rounding up witnesses to an elephant walking through the room. And that's my point: the evidence for the safety and efficacy of a vaccine that BILLIONS of people took should be impossible to miss; the fact that this evidence isn't obvious is the problem. I should be struggling to find ANY unvaxx'd population that's doing better than the vaxxed, not the other way around. So I'm not arguing the particulars of your evidence; rather, I'm arguing a larger point: the evidence isn't what we'd expect, and that's a problem.
Look, if you told me an elephant walked through a crowded room, the fact that you could find a FEW witnesses who saw the elephant wouldn't reassure me at all. If 3 or 4 out of 100 potential witnesses saw that elephant, I'd doubt those witnesses - I wouldn't assume that they were more perceptive.
To illustrate my point by analogy, if I developed a safe & effective vaccine for cancer, you wouldn't be struggling to explain why cancer deaths hadn't dropped, nor would you struggle to explain why deaths hadn't fallen. Granted, COVID's never been as dangerous as cancer, so I admit some of it is that we were lied to about COVID in the first place, but the idea that we've been lied to isn't particularly reassuring now is it? I mean if they lied to us about COVID why should I trust them about the vaccines?
The problem here is that you're telling me an elephant walked through a crowded room and only 3 or 4 people noticed because you know elephants - it's hard to notice when they walk through crowded rooms. Your story doesn't make sense. What should be clear and obvious is obscure...WHY?
It's interesting how you devote so much of your time to insulting your opposition; they don't do anything like that at all (in fact, they speak respectfully of you & link to your cite). In your experience, does the guy who's hurling all the insults have the better of the argument?
More importantly, I'm interested in the structure of the argument. If vaccines are safe and effective, then why do you have to go to such lengths to prove it? Shouldn't you simply be able to say, "Here's the COVID death rate and overall death rate in vaccinated populations and here's the COVID death rate and overall death rate in unvaccinated populations; now, it's not true that the former always beats the latter, but the trend's clear - it's not a correlation of 1, but it's awfully close"?
Instead, it's all sorts of excuses about why the expected correlation can't be found. (You didn't know that Israel is just a much healthier place to live? You do now!)
Again, is that the hallmark of the truth? Is your struggle to find POPULATION level data that proves your claims just something we should ignore? Should we fail to notice that you have to speculate over and over again as to why the POPULATION data doesn't fit your theory? You can tell me all the problems w/ the various studies; you can point to studies that "prove" your point, but you can't point to any real-world population level data (because that's messy or filled w/ confounding variables or whatever).
Sure, your story is possible, but is it truly plausible?
The unvaccinated aren't dead. Or dying. The vaccinated aren't living. Or healthy. At least, there's no discernible trend on each side's health. It's impossible to id a high vax or low vax population merely from their COVID deaths or overall death. If anything, low vax = better health as the African countries have great COVID #'s and low vax rates. (Again, not claiming this proves vax is bad; just saying that there's a disturbing lack of evidence for your side where there should be evidence for your side.)
Do see the problem? It takes - according to you - an extraordinary amount of expertise to see the benefits of vaccination, which doesn't make any sense. Your side should be obvious; my side should be struggling to find real-world proof.
Long and short, why are you struggling to explain the UK? Shouldn't that be obvious? (Like the general trend (which favors the vax) isn't seen here because everybody knows tea kills and they love tea or some other UK specific explanation).
I mean from my perspective your entire analysis fails the obvious counter: the UK keeps better stats and has publicized them more. Since there's every reason to believe Israel either doesn't know (worse stats) or lies (same stats but less transparency), why isn't THAT the explanation? The fact that you don't even mention the stats issue but talk about Israel's climate instead tells me that you were driving to support a specific conclusion.
To me, this is sort of a who are you going to believe - your lying eyes or me, the expert - situation. The real world should confirm your theories; it doesn't, so you keep trying to "explain" why the real world isn't as reliable as your theories. I have a problem w/ elevating theories and lab results above the real world.
"your immune response has ceased to be trainable"
Even if true, the author appears to have misplaced the caveat "for this specific virus". Sneaky sneaky!
"a new pathogen with more than 30 mutations on the S protein evoked NO new immune response"
I read somewhere (I think it was up to Delta variant) that the T-cell epitopes had not changed at all. Cannot find that page / study now, but searching for omicron t-cell epitopes turns up
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8764507/
T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant
where they observe, " In the Omicron variant, 80.4% (74/92) and 94.7% (178/188) of epitopes from the spike and nonspike proteins, respectively, were fully conserved, and 90.0% (252/280) of CD4+ T cell epitopes were completely conserved. These results indicate that the majority of T cell epitopes are considerably conserved in the Omicron variant."
Mentioning "30 mutations on the S protein" is all well and good but if said mutations do not change the epitopes the infected / phagocytic cells present to T cells via MHC then it's pretty much irrelevant.
My understanding is, B cells most reliably respond to **new** threats via T-cell co-stimulus. If T-cell stimulus remains largely unchanged (because the epitopes are pretty much the same), then to my way of thinking, "NO new immune response" is exactly what you'd expect.
I didn't meant to imply that the author was in full-blown VIAIDS territory, just that "ceased to be trainable in the context of this virus" is already absurd to claim based on... 8 monkeys that demonstrate the opposite of the claim anyway. Maybe I'll add a disclaimer so that I don't appear to be strawmanning.
Skipping to your last graph - and likewise, that is what would be expected if so-so antibodies reduce immune stimulation. IRL, the term for this is "immunity." But in IRL IRL, the immune system is not centralized so there's never any "one" response. Both antibodies and T Cells are leaky barriers, so there's a permissiveness, as well as a paper rock scissors interplay once you throw in innate immunity with the fascinating result that memory immunity takes a "back seat" after antibodies fade (antibodies (expire)-> innate immunity (if fail)-> resident t cells (if fail)-> ramped up antibodies and new gc-trained immune response) but the implications of this are not generalizable (since every pathogen is different) beyond the statement that "it allows for a lot of different dynamics."
Of course, (variant) vaccination circumvents the middle two stages, and more promptly activates the first part of the fourth stage, reducing the activation of the second part. However, even this is not generalizable. The omicron-boosted macaques defied OAS by not re-upping their WA1 response as much as the 1273-boosted.
Ironically, it feels like many people who have clung to OAS have themselves become a one trick pony. I think we need to come to terms that Substack operates no differently than any other forms of media such as YouTube or Twitter, and because of that people have typecasted themselves to continue to cover topics that they believe provide them with a lot of attention. It's likely why OAS has sprouted up all over the place as a justification for what's happening with these vaccines, mostly because it may provide them some position in the dissenting COVID narrative. I think because of this they may not be able to let it go instead of examining studies and taking a more cautionary approach.
Indeed - that was the theme of my Groundhog Day allusion! Besides the social media engagement-chasing aspect, both of the authors I have taken aim at here pass notes with each other and so there's a groupthink aspect. And just like both could probably read one sentence I write and tell I don't understand statistics / whatever it is that the other one does, it is obvious that neither reads much immunology research.
I will admit that immunology is so far above me that I generally struggle with much of these antibody and vaccine studies, so I do appreciate your ability to look into the methodology and raise pertinent questions. It's really the methodology that provides evidence as to the generality of the study.
And if you're wondering why I'm responding 3 months later, it's because I've been looking into OAS again to reexamine a few points. Although my position hasn't changed I'm seeing OAS pop up in the mainstream in regards to these new Omicron subvariants. What an interesting turn of events, even though I don't find the evidence to be all that convincing in favor of OAS.
I think I've been noticing the same thing, but I am barely keeping track of my own reading. I'm aware Mobeen highlighted another totally statistically fabricated prior-coronavirus-imprinting study from this winter, but at least seems to stay on topic RE "perpetual variant vaccines" which is the only context in which prior immunity can be portrayed as a "negative."
"Bartram" highlighted https://www.science.org/doi/10.1126/science.abq1841 which is just a load of nonsense - no unvaccinated Omicron infected set to actually compare with, yet tons of impossible to even parse conclusions about the effect of vaccination. *edit: Ok I was too hard on the paper, in that it isn't trying to make too much of its own results; it's still weird that the unvaxxed HCWs weren't compared in general and that Fig S5B doesn't compare the Wuhan+Omicron response to even a single other type of +Omicron response.
It's infuriatingly stupid on a really fundamental level. Like just a basic inability to be logical and persistent intentional lack of precision in language in all the OAS lit (except for maybe Yewdell's review). Just to get something published.
Boy that's a chunky paper, and so is the supplemental material (which I usually miss!). I am finding it hard to figure out some of these issues. It only came up because I wrote a post on the widely cited chicken study and a few commenters were discussing OAS.
Then I went scouring a bit and didn't realize the level of "immune imprinting" papers that have been released. Aside from the nonsensical inclusion of the N protein in the analysis of OAS, I find it strange that pro-OAS people haven't addressed the role of seasonal colds in OAS. I mean most of us here are adults so it's far more likely that we came across the common cold before COVID. At the time that we are blaming continuous vaccinations why is no one blaming the cold they got when they were 3 years old on imprinting those spike antibodies?
But like I said, your analysis of these immunological papers far exceed my own so I just decided to go digging into your old posts to see if there was something I was missing.
Wow substack supports jump-links by default now, very cool - https://moderndiscontent.substack.com/i/60311971/transmissionvirulence-trade-off-hypothesis - guess it's the end of my year of manually creating footnotes as link anchors.
I wrote about Marek's, my comments are similar to Bull, J. J. & Antia, R.'s point 4 - https://unglossed.substack.com/p/crackpot-corner-marekspocalypse-edition
I also like your point that MDV seemed to already be gaining virulence spontaneously. And history is full of such spontaneous changes in "virulence" (as measured by the constantly changing instrument of the host species's health). Hopefully I'll be getting back into that kind of evolutionary / immune equilibrium theorizing soon.
Ah, I'll take a look at that paper! I'm writing one on reinfections, and I'm ashamed to say I think a bit of immunological trickery may have been afoot with the messaging about immunity. I blame a lot of this on the use of "novelty" in describing this virus and for us believing that a natural infection would lead to permanent immunity when respiratory infections have never done so.
Yeah the MDV part was mentioned directly in the study. I don't find it reasonable to argue that vaccines may have been the cause when the authors mentioned that lymphomas were emerging almost 2 decades before they initiated any chicken vaccination campaign. But to steelman the authors, they do argue that the imperfect vaccination may not have drive the virulence, but may have helped maintain it by increasing the survivability of the infected chickens.
I love how you get annoyed on things I would not even notice. I keep coming reading you because I really don't know what your position will be on anything until I read your position.
Haha, well I'm pretty predictable on the OAS subject. On other stuff I am sure I appear wildly ambivalent - but mostly I'm just trying to not pretend the replication crisis suddenly isn't still ongoing...