Apr 30, 2022·edited Apr 30, 2022Liked by Brian Mowrey
I haven’t been following you so I have no idea what your track record is. Not that it matters because I am only commenting on this post.
I think you are right. At the same time, the risk that you may not be is sufficiently appreciable for the vaccine rollout policy to have been reckless, regardless of what eventually transpired.
Personally I strongly suspect that numerous respiratory viruses are currently circulating for reasons more related to lockdown policies and related reactions than to either Covid or the vaccines.
I hypothesise that people getting tested to exclude a Covid reinfection are mostly getting false positive PCRs due to the earlier infection. Is there any reason not to entertain this hypothesis?
I don’t believe the current “Covid” numbers at all.
Do you mean "right / may not be right" RE OAS? On this one very limited "risk," the burden of proof was never on the Covid vaccines per se anyway, because it was essentially a total speculation, not actually a known unknown but an imagined unknown, which is the same as an unknown unknown. In other words, there's no evidence OAS is real, so it is not a known risk.
But that doesn't matter, because unknown unknowns are also a valid reason not to launch mass medical experiments on humanity. So the fight to legitimize mythical OAS and then peg it onto the Covid vax misses the point, or is more like wishful thinking as far as how easy it is going to be to identify and prove the harms caused by the vax, as if it can actually show up in an assay as simple as "N antibody +/-." Won't be that easy. What are the harms from older vaxs? Oh yeah, it's really hard to identify. But they're probably legion.
I agree PCR+ <90 days after previous should be considered likely false+ due to the high rate of false+ and low rate of true+. Even a sequence resulting in a putative reinfection could just be detecting an abortive reexposure / reinfection and associated symptoms could be from something else. PCR seems to actually work ok as a diagnostic during waves and not otherwise or for reinfection.
Thanks for your reply. Yes, I meant right in arguing that the data is being misinterpreted by some to find evidence of OAS, and that such evidence as there presently is, is not supportive of such a finding as it has other, more natural interpretations.
I was not aware that it was disputed whether OAS was a phenomenon at all, happy to learn more.
There isn't dispute, there's just plenty of evidence on the "no OAS" side (refuting a hypothesis means the hypothesis is false, that should be the end of the discussion) and a lack of "yes OAS" evidence that exceeds "defining immunity as OAS." So you prime someone, then show that later they don't just literally totally erase that immune response, you say "look it's OAS." What? That's just immunity. Essentially the same gimmick in https://unglossed.substack.com/p/even-steven
Not on either side are the papers about OAS in the mid-20th (Francis, who coined the idiotic term as if merely to "blame" the immune system for his decades of failure to make a flu vaccine) which don't actually test the theory. Then you have the attempts to test the theory in the recent revival of interest (why? why suddenly try to prove an relatively ancient theory that wasn't apparently relevant in any of the intervening decades? this is not normal in biology) the results of which are summed up by JW Yewdell in Table 1 of http://perspectivesinmedicine.cshlp.org/content/11/5/a038786.long Note that this paper doesn't frame itself as "disputing" OAS, and calls Francis's coinage of the term "brilliant." Ha.
For subtext, Yewdell is an NIAID lifer who has been researching influenza forever, and this is the only paper, I would guess, where he even mentions OAS. *edit: He turned out be on a paper mentioning / testing imprinting in 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360521/ in Fig 7C, which is monstrously difficult to read but turns out to refute OAS RE 8 of 8 flu HA antigens in two 4-mutant infection followed by wild type vaccination experiments.
Some points you may or may not be aware of. Vaccines meh at best. Clean drinking water and a proper sewage system fixes most of what vaccines purport to do without the side effects. Remember the guy with swollen balls? Known possible outcome of the mumps vaccine as it's protection wanes in young adult males. More properly known as the adult reaction to getting the mumps in young males. Mumps is nonlethal as is chicken pox. Smallpox outbreaks are tiny and overblown. Polio and Ebola are passed by feces. The HPV vaccine are causing cancer clusters in young girls.
HIV is a well documented scam. The mRNA virus appears in half the population randomly and is not harmful on its own. AIDS should more properly be called oxidation poisoning. As that was the cause of the initial few cases. The organ failure and death in non oxygen poisoned individuals is caused by the approved treatments. The tests to get you into treatment are entirely subjective.
I am aware of those points, yes. This is why I don't frame my discussion of the Covid vaccines as "they aren't like those other really good ones," "they are leaky, unlike previous vaccines, and thus will have unprecedented effects," etc. All vaccines except maybe Sabin polio are probably net negatives imo.
Obviously, you'll tell me that COVID really isn't that dangerous to people in my age category; in other words, you'll tell me that nothing the media or government said about COVID was true. Uh, so why should I trust what those same sources are saying about the vaccines?
Literally, your argument is that I should trust the vaccines because I should distrust everything the same sources told me about COVID.
My question, therefore, is were you lying then or are you lying now? Or were you merely stupid then, but now you've figured it out?
Look, the fact that I'm unvaccinated & alive means that SOMETHING you COVIDIOTS told me was wrong, either because you were idiots or because you were lying.
Neither explanation comforts me.
At this point, based solely on the evidence, I have to infer that you either don't know what you're talking about or you do, but you're lying. Either way, I have to presume you're wrong.
At the very least, you need some serious mea culpas here.
Having been wrong about EVERYTHING for 2 years now, a little modesty is in order.
Because just as you're now basically conceding that COVID was NEVER that dangerous, I don't want to be back here in a few years when you have to concede the vaccines were never as safe & effective as you claimed.
You've got to be careful with the UKHSA / SIREN reinfections data -- they specifically excluded BA.1 as being a reinfection candidate (ie, if they had a sample with BA.1 more than 20 days after BA.1 initial infection it was regarded as the test finding remnants of the original infection, not a reinfection). They didn't find much in the way of BA.2 because there wasn't much of it in the country at the time.
This isn't 'proof' -- just shows that it is necessary to do the investigations properly.
OK I see where the Flu report uses variant differentiation for the possible/probable distinction (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1072072/Weekly_Flu_and_COVID-19_report_w17_v2.pdf) but that's for the 90+ day PCR+ reinfection set, it's not clear that it would apply to the VOC analysis. The text of the VOC analysis suggests that there were no censored sequence events. "Preliminary analysis of 496,228 cases of PCR confirmed SARS-CoV-2 infection between 27 December 2021 and 16 January 2022, when Omicron BA.1 was predominant, identified 186,896 BA.1 confirmed cases with genome sequencing. Thirty-one of these cases had another subsequent sequenced sample with an interval of at least 20 days after a previous positive test, with a maximum follow-up period of 72 days."
Thanks, I’ll review the document and add a note. Presumably a censored BA1 reinfection value can be estimated using the BA2 number, which should still show a fairly unconcerning rate
I’m sick of skimming long articles full of scientific jargon so I’m just going to assume you’re controlled opposition on the payroll of Pfizer. I guess we’ll know for certain once the vaccinated are decimated by OAS this winter.
I’m tired of reading glowing compliments so I’m just going to assume this is another glowing compliment, as to do so can’t present any possible risk of misinterpreting you on a fundamental level. Thanks, that’s very kind!
Have you seen this (just published last week): https://rdcu.be/cLc7b ("SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells")?
From the abstract: "Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory."
It seems to me that these findings further refute the hypothesis of OAS (at least pre-omicron). Just wanted to call it to your attention.
Fantastic - "individuals after breakthrough infection mount vigorous non-spike-specific responses." That's the UKHSA N protein comment blown to bits. N antibodies are higher for the breakthrough set than for naive infected in Ext Fig 1a. Thanks for the tip!
I'm not sure that expanding and differentiating spike memory should be assumed to be a positive (there's always such a thing as overkill), but it's also not a surprising result given Röltgen, et al.'s Fig 4.
Long time reader, first time commenter here. I tend to agree with your take on OAS and your theory of innate immune suppression. It jibes with what G.V. Bossche says, plus it jibes with what I've been observing anecdotally. Two things:
1) Have you seen this most recent study out of Germany: https://www.biorxiv.org/content/10.1101/2022.04.01.486695v1. It's entitled "Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation." They found that Omicron post-vaccination infection mediated a robust B-cell recall response, and primarily expanded preformed memory B-cells that recognized epitopes shared broadly by different variants, rather than inducing new B-cells against strictly Omicron-specific epitopes. Wouldn't this study be more evidence that OAS is not what is occurring?
2) Re: spike protein shedding of vaxxed onto unvaxxed. In the past you've discussed this phenomenon. I have observed (and experienced) it anecdotally. In light of our innate immune suppression theory, could it be that the unvaxxed who experience cold-like symptoms after being around the vaxxed are not having a reaction to shed spike protein, but rather are experiencing an innate immune response to omicron itself? If the vaxxed have suppressed innate immune systems, they could be infected (to varying degrees) with omicron but aren't experiencing the mucousal (innate) compartment response (i.e. no symptoms). Thus, the unvaxxed, especially one who had a previous infection and has innate immunity memory intact, would experience an innate immune response after having close/extended contact with an infected vaxxed individual (who is ignorant of it). I could elaborate more, but wanted to run it by you.
1 - I've seen it, yes! It certainly refutes OAS, though not with a perfect setup. For example comparing 2d+Omicron breakthrough to 2d+1d proves the variant doesn't just "recall" the vax response, though I would like to see results for 2d+pre-Omicron breakthrough for a better comparison. Also it was orchestrated by BioNTech, pretty big conflict of interest haha. Still I'm working on a writeup.
2 - That model is technically plausible. There is someone who employs it frequently, I forget who. For me, I'm a bit skeptical that innate immune suppression would drive asymptomatic-ness, rather than the opposite. Robust innate immunity drives asymptomatic-ness. If the virus is replicating then it is destroying cells and activating inflammatory pathways. So the general dogma that the "immune response causes symptoms" has always struck me as blaming the firemen for the fire.
As for the unvaccinated, they may be in a grey area between innate and adaptive response + small doses of virus, and in that grey area you could model a recurring innate immune stress/training scenario. But... I'm inclined to think that the memory immune system has built-in ways to insinuate into innate immune response even before said response is "overwhelmed." For example lymph nodes are lined with CD169+ macrophages, a very passive immune cell that can culture viruses to promote their growth within the lymph node and make antigen presentation and germinal center formation more likely (https://www.frontiersin.org/articles/10.3389/fimmu.2018.02472/full) - so contra GvB, it does not seem like evolution wants to do everything it can to prevent formation of tailored antibodies to respiratory viruses.
Again, it's still a plausible model. But my guess is that repeat exposure to the virus would tend to generate antibodies in the unvaccinated and then the virus would stop being a bother at low doses.
An alternate model is that exposure to expressed spike would act as a respiratory toxin regardless of antibodies, the same as LPS (organic dust) in constant doses. Toxic stress on respiratory cells could lead to positive feedback loops with the microbiome where you get to dysregulation (bacteria converting to more pathogenic phenotypes, or disruption of bacterial antiviral-immune-promotion - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381240/), and so now even the unvaccinated are more susceptible to colds, or scratchy throat, or who knows what. But I'm not sure if that's convincing. Expressed spike could be more akin to an irritant / allergen unless in super-high doses, who knows.
1) Agreed. I would like to see results for 0d + Omicron infection or previous infection + Omicron breakthrough. But, they probably wouldn't like those results: that would show natural immunity is more robust. ha ha
2) Agreed. However, what is interesting with the anecdotal evidence I've observed is that the unvaxxed experience cold-like symptoms a few days after or into intense/prolonged exposure to the (triple) vaxxed, yet are not testing positive (e.g. my daughter is a previously infected unvaxxed RN, who in Jan and Feb (when omicron was severe here) would get "sick" the last day of her 3 day shift but would be fine after a few days off, only to repeat the cycle when she returned to work again a week later (and she never tested positive for covid)). Would such a delay in "symptoms" comport with the alternate model you suggested? Or, could such a delay be possibly due to the innate immune system (non adaptive) B cells taking a few days to produce new/more IgM abs in response to the re-infection? From what I understand, these IgM abs are short-lived and would disappear once the infection is cleared (and theoretically would re-appear when an omicron antigen is once again detected in the nasal or throat passage).
Actually, that setup is partly contained in the Austria Omicron study (https://unglossed.substack.com/p/the-austria-omicron-study). Here the small sample size seems to drive unexpected results, but either way it also refutes OAS. Both injection and previous infection outperform the naive group in post-Omicron anti-Omicron-neutralization.
2 - Yes, that would fit in a "spike as toxin" model if the part about toxicity->microbiome dysregulation->downregulation of antiviral (or even anti-fungal) innate immunity turned out to be the perfect solution. After exposure to the spike goes away it takes a few days for inflammation to settle down and microbiome promotion of tissue repair to turn back on. But once again the "innate stressor" model also works, it's just that I tend to think adaptive immunity would kick in in that case. Essentially my instinct is that adaptive immunity / antibodies are designed to give the innate immune system a rest from the virus-of-the-season for exactly this reason, you don't want to stress it long term.
You may be right about IgM, my understanding was that the mechanism of generating IgM is not well understood but that could be a gap in research on my part. Note that natural IgM also participates in directing antigens to germinal centers (https://www.jimmunol.org/content/jimmunol/194/1/13.full.pdf) which again implies that evolution wants the adaptive immune system to insinuate into innate antiviral response as much as possible.
1. Right! I remembered that study shortly after I replied. [BTW, you're analysis of it was excellent!]
2. Thanks for the followup explanation. I guess the whole phenomena can be put into the "who really knows??" category. FWIW, I have not observed that phenomena since March 1--round about the time omicron cases radically dropped off here in Ohio AND/OR three months after most Ohioans got their booster (although only 30% got boostered). So, my anecdotal evidence could support both models: either a) the vaxxed finally cleared the virus and are not re-infecting others, including the unvaxxed (the "innate stressor" model); or b) with the booster waning, the spike proteins levels in the vaxxed have significantly dropped (the "spike as toxin" model).
Notwithstanding the cause of said phenomena, there is something we've both touched on that I think needs to be explored (and also ties back into your original post): the role of IgM and (mucousal) Secretory IgA (SIga) abs in the innate immune system. Is it possible those abs are being suppressed in the vaxxed (which is causing the issue in the UK right now)?
It is my understanding that both are part of the innate immune system--they are not custom-made abs in response to a specific antigen (and therefore are not considered adaptive), but rather show polyspecificity (i.e. they weakly bind to to a large variety of epitopes in a variety different antigens).
Studies have shown that the vaccines produce little (if any) SIgA abs. Is this (partly) why they are getting (re-)infected? And, could it be that their B1 cells are not expressing/secreting IgM abs (which you explained here: https://unglossed.substack.com/p/neg?s=r), so that their first line of defense against omicron has been effectively disarmed?
The "my take at GvB's nAb theory" model in Neg proposed that residual leaked IgG (circulatory IgG leaks passively from plasma to mucosa, which is why the injection produce short-term infection efficacy when plasma IgG is really high) was outcompeting nAbs and thus leaving innate cellular immunity in the dark. This doesn't really fly since it turns out IgG cross-engages with innate immune cells; so there shouldn't be any point during IgG fadeout where you get to negative efficacy via out-competition. So, pending more research, I'm hewing to the KISS model of innate immune suppression: the vaccine just makes recipients unhealthy. It wears down their bodies and exhausts their immune systems. Same as the party lifestyle of the original 80s AIDS crowd.
A little anecdote which may support your KISS model:
Prior to a third (booster) jab in mid-December, a friend (who is fit & healthy; rarely sick) had a WBC of 7.67 and a lymphocyte count of 1.69. In mid-March, those numbers increased to 10.3 and 2.8, respectively. Other than a week of cold-like symptoms (perhaps a mild bout with BA1 or some other cold) in early February, there was no appearance of any infection or sickness (i.e. asymptomatic) at the time of the CBC test in March. While 10.3 and 2.8 are not high enough to be in the leukocytosisis and lymphocytosis categories, they are on the high end, indicating (to me) that the immune system is fighting some sort of infection (even though there are no symptoms of infection).
Could this be a signal of the body getting worn down and immune system getting exhausted? Makes me wonder.
So leaving all the acronyms aside, what do you project might happen if people got a measles vaccine every three months for a couple of years? Would the immune system stop recognizing measles as a threat? Maybe see it as part of the larger organism? Then what might happen if there were a slight mutation to the virus...nothing too obvious to the immune system but enough to make a significant impact to the organism?
Artificially induced immune tolerance is largely a theoretical subject, so all I can do is theorize. But I would bet on very little long term immune impact. Essentially the immune system at the end of the two-year course would be the same place as if it had received just a single dose close to the end of the same two year period (and didn't encounter the virus in the wild in the meantime). For the young there would be some long-lived memory B Cells that will last forever, and a short-term high antibody level that will fade out over time regardless of how many shots one had before the end of the course.
Essentially what I would assume is that during each boost, the previous memory B Cells and antibodies continue to be such a good match that no new immune response is generated. When existing IgG antibodies are a good match for a circulating antigen, it outcompetes IgM, preventing the antigen+IgM+C3 complex which activates the "switch" that tells B Cells to traffic the antigen to germinal centers FDCs to say "hey make a better immune response to this." So the re-injected Measles antigens are handled by the previous immune program and things don't devolve back to the executive level (antigen presenting cells and germinal centers) where a new immune response can be formed. Likewise, since the gut microbiome isn't involved, there's little risk of inducing tolerance. On the other hand, a little bit of "spillover" into novel executive-directed immune response leading to autoimmunity for some recipients, sure, maybe; and there could be direct autoimmunity from constant high anti-measles antibodies leading to immune response against whatever self-proteins they resemble, etc. So that's there, but I wouldn't rate it as likely a universal danger.
An mRNA / DNA measles vax might be different, because maybe it would be cells in the GI tract that express the proteins, maybe that could cause some cross-wiring and tolerance, who knows. And so same for the Covid vaccine boosters, maybe there is a good risk of tolerance. But for an "inactivated" virus vaccine, I wouldn't bet on it.
So a difference between a sterile and living vaccine? I also wonder about chemotherapy. It often works very well at first but after time tolerance occurs and the mutated cells no longer respond (by dying) and in fact may even accelerate replication. Adaptation and tolerance seems to be a response to all kind of organisms vs molecules. (antibiotics) not beneficial. I know I am rambling but trying to understand the difference here.
A little bit. A "live" vaccine is really just a functional virus. I also misspoke because the Measles vax isn't "inactivated," just super-attenuated and a bit cell-culture-evolved (it targets slightly different receptors than the wild type). But at the same time, "inactivated" is just a euphemism for chemically treated (and possibly still infectious), so all you can really say in general is that you don't want something that is injected into the blood to have too much kick.
Whereas the main vaccine we would think of as a "live attenuated" is the Sabin polio, which is delivered to the GI tract so it pretty much mimics natural polio infection. Sorry for muddying that up, I should have just used "whole" injected virus.
The distinction I really meant to draw is that the mRNA vaccines don't "wear" their own antigen, so anti-spike antibodies don't prevent the LNPs from getting into cells and making the cells produce more spike. This might lead to tolerance or autoimmunity for a variety of reasons. But a "whole" injected virus wears the antigen, and so when it is reinjected, antibodies block it from entering cells. Memory B Cells ramp up even more antibodies, but there's no or very little "new" immune response.
Apr 5, 2022·edited Apr 5, 2022Liked by Brian Mowrey
While I agree with most of your concerns about the validity of the N seropositivity data (it would be better to get a more explicitly uniform sample), I would also point out that the higher seropositivity by age tracks very well with the lower vaccine uptake by age. For example, the 17-30 age group is probably around 65% vaxed, and the uptake has risen fairly recently - so the lower uptake combined with the odds that they were infected prior to vax would seem to comport with the data on N positivity. At this point, as it appears that 10% of the UK population seem to have C19 at any given time, isn't it surprising that N positivity still remains down under 40%?
As for why UK seems worse than New England - I think the high vax rates in New England are biased along socioeconomic lines - in the highest density areas, higher likelihood of vax corresponds with higher likelihood of remote work. In my workplace it's got to be close to 99% (myself being the only refusenik I'm aware of) and the office is probably 20% occupancy on a busy day. These people don't live in the denser areas - and most of the poor folk who do already got infected last year, and are on balance less likely to take the vax (hey - they aren't overeducated idiots after all!)
The UK is overall 3.5x more densely populated than New England, and NE may have a bias in vax uptake to more wealthy suburban, zoom class populations. Some other differences include UK having a more homogenous population, substantially higher latitude, and a different mix of vax types, with higher prevalence of Astrazenica. I would also point out that while less dramatic, the Mass. new case rate has not hit 0 since July 2021, the lowest new case rate since then has been 30/100K after Omicron swept through. So basically the problem does exist there too.
Your point about the network effect is very important. I think this is also an important factor in your disagreement with the "worry window" concept. You point out that the worry window / immune suppression is a small effect. This is true. But it does exist - and I submit that this small effect, when combined with the network effect, leads rollouts to create outbreaks. This produces the very obvious signal in the data that people latch onto, and sometimes then want to over-estimate the actual effect of the immune suppression.
it was a good intro to the impact of pseudouridine which I found very enlightening. I still need to read the source papers to understand it more fully. One thing I remain puzzled about though - the effect described here seems like an intra-cellular effect as a result of the transfection - so once those cells get killed off in the immune response, why would this effect persist for longer? Maybe the answer is, it doesn't persist. But then why do we seem to continue to see signs of long term immune suppression? Psuedouridine does not seem to explain the whole story here.
So, that goes back to part i of the original UKHSA comment in October, which is the part that correctly explained the trend - the donor sample is not reflective of real world vax rate. Donors are “do our bit” types. Note that overall S seropositivity is already near-100% by mid-2021. So there were almost no unvaxxed donors after mid-2021 and so the low N-rate would appear to be a portrait of what is happening to the vaxxed (when in fact it is only what is happening to the infection-negative vaxxed). Likewise, there are no apparent dips in S seropositivity in the last months so the upswing isn’t a result of any dirty, selfish unvaxxed reentering the donor pool. Now for the youngest group almost half of (vaxxed) donors are N-positive. Besides residual selection bias there’s probably also antibody fadeout (whereas S seropositivity is propped up by boosting even among the not-recently-infected), and a lot depends on whether the “positive” threshold for both assays is equally sensitive.
Yes, I agree with all of those points about New England, and have noticed the MA persistency but hesitate to rule out a testing artifact given that NY isn’t in agreement.
As for worry window, the converse Network Effect interaction is that swings in innate/adaptive immunity are happening all the time, in fact that is a plausible mechanism for explaining seasonality. So if you send a ripple through the network when innate/adaptive immunity is rising (as at the end of a wave), you don’t make a difference, and likewise if you send a ripple at the beginning of a wave (the wave was going to happen anyway). And the “window” is a ripple by definition since it is short. You would have to introduce the ripple into a equipoised system to make a difference, and in reality there is no equipoise, only equilibrium. Besides that, the evidence for the ripple itself isn’t even strong, imo.
Right, I think the pseudouridine doesn’t explain persistent effect and the “60 day mystery” solves why it is detected in germinal centers. So we can assume a short half-life. Long term effects, including immune suppression, are probably a lot less elaborate in mechanism. Ok, you’ve got endothelial inflammation, fibrosis here and there, long-term metabolic dysfunction - so the immune system is worn down. Same as for long-term drug use in the 80s leading to AIDS when combined with network effect (and spilling over to non-users in the same network once the critical mass was reached).
Apr 5, 2022·edited Apr 5, 2022Liked by Brian Mowrey
Hi Brian. I just woke up (will go back to sleep asap) and saw your article! Love the controversy and your, as always, politely stated and carefully argued opinion.
This is what the debate should always be, as opposed to abuse or attempts to "cancel" their opponents.
That said, you make two statements:
1) OAS is not real
2) The UK's endless Covid is "immune suppression" driven, saying that there is a network of immune suppressed persons, that is big enough to drive a wave of endless cases.
I want to leave 1) aside for now because I need to go back to sleep.
However, regarding 2), you are likely to be completely right and spot-on in identifying ANOTHER problem in the UK: a critical mass of generally immune suppressed people having colds from hell, endless covids, and soon everything else, and endlessly infecting each other.
It is not just the UK's (or "the isles") problem. In Germany, the endless covid is even worse than in the UK, or perhaps the Germans do more tests, but clearly Germany has a endless covid problem also. Israel's graph of cases this year is similar to UK's. The only no-longer-important difference between UK and Israel is last November.
The US seems to be the exception. It may be so because the US is especially bad at keeping national statistics, but it could also be for other important reasons. We'll explore it later.
The bottom line is your immune suppression story is not something I am objecting to, and in fact I support it 100%. There is immune suppression indeed and we are seeing it. After three vax doses and three covids, the immune systems of such unlucky people will likely be severely suppressed, which is kind of what I kept on saying and screaming about too comparing Covid with AIDS.
Not sure how many spike protein transfections (vax or Covid illness) is enough to cause immune suppression, it could depend on luck of specific persons, but clearly, the more the worse, and the effect is cumulative, leaving people worse off after every episode.
We have a health emergency that is likely real and likely will end up badly, and we need to warn as many people as we can about it.
The ability of chronic stress to undermine the innate immune system could be a factor. There have been studies on this in students showing those under stress are more susceptible to colds (I think it was somebody called Cohen who did this research). What have we been subjected to over the last 2 years? Fear! Fear of the virus, fear of being forced to get injections, fear of loss jobs etc. The population has been chronically stressed for the last 2 years. I can attest to my own health, which is by no means bad, still being worse since this pandemic kicked off despite not being vaccinated nor testing positive for COVID. I just seem to get minor infections whereas I didn't used to do. hardly at all. This is despite taking active measures, more so than I have ever done before, to bolster my immune system with supplements etc.
Thanks - actually, I wasn’t sure whether I should add repeat-dosing to the theory. It may be the case that the UK would be in the same boat if everyone stopped at 1 dose, or at least there may be “diminishing negative returns” on the later injections. It remains good advice to stop the injections ASAP either way! However, using the building analogy, the only solution (if there really is an emergency of innate immune deficiency going on in the UK and now maybe West Europe) besides getting out of the building is for everyone to try to improve their innate immunity. Doubt either thing will ever happen.
Good catch RE Israel - I hadn’t looked at cases there in a week or so. I might have to fix my text.
Thank you, I really appreciate it when substackers give a different views from one another. It keeps my mind open, and we all get better information. 👍🏽💕
There's a lot to say about the constant re-iteration of OAS. Just like I have said previous (and you have mentioned) it's like those ardent supporters of OAS are stuck within their own proverbial OAS. It just feels like something I've been increasingly concerned about where it feels like people are collecting information but generalizing further than they are allowed based on the evidence presented. It also doesn't quite make sense why OAS keeps being used to argue the immunological effects of targeting a completely different antigen.
One thing for people to keep in mind is that the concept of the N line being flat is "relative" and is likely affected by the scaling to accommodate the S curve- if you compare it from the start of measures you can see that it doubles.
The higher increase within the younger demographics is also to be reflective of older people being vaccinated first and the younger group not having it available for several months. All this suggests to me that, because the N protein is sequestered within the virus, it may be that the host is not experience the full exposure of the virus' antigens such that the anti-S spike may be removing the virus before the N protein can make itself known.
And quite frankly, I'm getting rather tired of the seeing this large dependency on case numbers. I thought many people have, rightfully, criticized the veracity and accuracy of these tests. Why do these people then rely so much on this as evidence for their narrative or ideas? Either PCR tests are faulty and we don't rely on them or they are accurate and we can trust their results. They can't have it both ways.
As noted in my reply to Jon, I’m usually careful that the case trends I discuss are of decent fidelity but leave out discussion of my methods here since it would be tedious for the reader. Besides that, I’ve actually been pretty bullish on PCR+ as a proxy for viral challenge since July, so there’s no “having it both ways” in Unglossed World, haha. I am provisionally not as sure if the same proxy is as valid for the Omicron siblings as for the Wuhan strains, however.
Right, lack of N antibody wouldn’t be OAS or even necessarily suggestive of a deficient post-breakthrough immune response anyway. Is N antibody even functional, or just a correlate for broader immune recognition? If the latter, then the correlate may simply turn out not to be as valid for the breakthrough immune response. All that matters is reinfection and afaik the best view of what’s going on there is still Goldberg, et al. - https://unglossed.substack.com/p/darmok-and-the-spike-protein-at-tanagra?s=w#footnote-8 - there is only a truly tiny increase in reinfections which can be attributed to the early breakthrough “mildness discount.”
Many of my grievances are not in your direction Brian as I can trust that you engage in a lot of sourcing and critical thinking! But it's more of the fact that even to this day it appears that case rates are still being plastered all over the place. If it's being used to validate the ineffectiveness of these vaccines then at this point that becomes redundant since that was figured out months ago. Are the same people who continue to utilize case rates the same people who have been critical of the accuracy of these tests? In which case I question why this double standard is occurring.
Right, you can notice that tension in a lot of the worry window / negative efficacy theorizing for example. One minute the injections are responsible for any and every upswing in cases, the next minute "severe efficacy" is a secret illusion created by the fact that the vaxxed "get severe Covid" without testing positive. Ok... sure...
Yupp, it's making me consider writing about this and opening up discussion. I guess it bothers me because it introduces a lot of noise into the discussion and clouds my ability to assess things properly. I just wish more people were consistent.
It's definitely the reason I don't ascribe to the "endless COVID" argument. If the intent is to gauge endless COVID based on PCR positivity then we would need to trace PCR tests back to an adequate number of people, see their positivity rates, see their severity of illness, and see their immune response. There's a lot more to it than just reading case rate graphs, and considering so many people have been critical about them in the first place I have to wonder why people have jumped onto them now.
I used to do PCR testing for COVID and my argument has usually been that it's OK for symptomatic people but in no ways should have been used for widespread testing and especially for asymptomatic people. I've been very critical of the mass testing and like you said greater testing means more incidences of false positive. This also really muddied the waters for what constitutes "Asymptomatic"- over 40% of people being asymptomatic seems more like the inclusion of a lot of noise rather than actual signals.
And like you said PCR tests have always been confirmatory, not diagnostic, which is also the biggest issue again with PCR it should not be used as the only assessment for positivity.
Right, I’m usually running envelope-math validations of any case trends I talk about at this point, and just not mentioning case trends that appear to be in false positive territory if I don’t have to. It would be very tedious to show my work here, but the gist is that unless the per-test positivity rate goes down than a corresponding upswing in cases is not an artifact of increased testing + false positives.
Right, and one reason for “walking away” from the UK stats was the possibility that it’s a test behavior artifact, despite the solid positivity rates since summer (which were solid despite rampant school testing). Here again the change in West Europe argues for taking the UK stats just a bit more seriously again. Ironically, at the same time they have just ended free testing for low risk groups so the forever wave will possibly die out anyway.
Echoing ForkInSocket, the pre-summer trend was that waves went to zero (though there was still a double wave in autumn/winter 2020 so I think we can grant double-waves as the geographic norm (some kind of effect of the UK’s super-suburban layout, combined again with lower baseline innate immunity than continental Europe); and then the spring 2021 lull was propped up by the happy valley of infection efficacy, and since July they’ve been living in the “infection purgatory.”
However, I want to be careful that the evidence is both circumstantial and heterogenous. The SARS-CoV-2 case rates don’t tell us how many “colds” people are getting, just the anecdotes. So explaining the case rates with innate immunity can’t rule out other factors; it’s just the one that’s consistent with the anecdotes.
I haven’t been following you so I have no idea what your track record is. Not that it matters because I am only commenting on this post.
I think you are right. At the same time, the risk that you may not be is sufficiently appreciable for the vaccine rollout policy to have been reckless, regardless of what eventually transpired.
Personally I strongly suspect that numerous respiratory viruses are currently circulating for reasons more related to lockdown policies and related reactions than to either Covid or the vaccines.
I hypothesise that people getting tested to exclude a Covid reinfection are mostly getting false positive PCRs due to the earlier infection. Is there any reason not to entertain this hypothesis?
I don’t believe the current “Covid” numbers at all.
Do you mean "right / may not be right" RE OAS? On this one very limited "risk," the burden of proof was never on the Covid vaccines per se anyway, because it was essentially a total speculation, not actually a known unknown but an imagined unknown, which is the same as an unknown unknown. In other words, there's no evidence OAS is real, so it is not a known risk.
But that doesn't matter, because unknown unknowns are also a valid reason not to launch mass medical experiments on humanity. So the fight to legitimize mythical OAS and then peg it onto the Covid vax misses the point, or is more like wishful thinking as far as how easy it is going to be to identify and prove the harms caused by the vax, as if it can actually show up in an assay as simple as "N antibody +/-." Won't be that easy. What are the harms from older vaxs? Oh yeah, it's really hard to identify. But they're probably legion.
I agree PCR+ <90 days after previous should be considered likely false+ due to the high rate of false+ and low rate of true+. Even a sequence resulting in a putative reinfection could just be detecting an abortive reexposure / reinfection and associated symptoms could be from something else. PCR seems to actually work ok as a diagnostic during waves and not otherwise or for reinfection.
Thanks for your reply. Yes, I meant right in arguing that the data is being misinterpreted by some to find evidence of OAS, and that such evidence as there presently is, is not supportive of such a finding as it has other, more natural interpretations.
I was not aware that it was disputed whether OAS was a phenomenon at all, happy to learn more.
There isn't dispute, there's just plenty of evidence on the "no OAS" side (refuting a hypothesis means the hypothesis is false, that should be the end of the discussion) and a lack of "yes OAS" evidence that exceeds "defining immunity as OAS." So you prime someone, then show that later they don't just literally totally erase that immune response, you say "look it's OAS." What? That's just immunity. Essentially the same gimmick in https://unglossed.substack.com/p/even-steven
Not on either side are the papers about OAS in the mid-20th (Francis, who coined the idiotic term as if merely to "blame" the immune system for his decades of failure to make a flu vaccine) which don't actually test the theory. Then you have the attempts to test the theory in the recent revival of interest (why? why suddenly try to prove an relatively ancient theory that wasn't apparently relevant in any of the intervening decades? this is not normal in biology) the results of which are summed up by JW Yewdell in Table 1 of http://perspectivesinmedicine.cshlp.org/content/11/5/a038786.long Note that this paper doesn't frame itself as "disputing" OAS, and calls Francis's coinage of the term "brilliant." Ha.
For subtext, Yewdell is an NIAID lifer who has been researching influenza forever, and this is the only paper, I would guess, where he even mentions OAS. *edit: He turned out be on a paper mentioning / testing imprinting in 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360521/ in Fig 7C, which is monstrously difficult to read but turns out to refute OAS RE 8 of 8 flu HA antigens in two 4-mutant infection followed by wild type vaccination experiments.
Some points you may or may not be aware of. Vaccines meh at best. Clean drinking water and a proper sewage system fixes most of what vaccines purport to do without the side effects. Remember the guy with swollen balls? Known possible outcome of the mumps vaccine as it's protection wanes in young adult males. More properly known as the adult reaction to getting the mumps in young males. Mumps is nonlethal as is chicken pox. Smallpox outbreaks are tiny and overblown. Polio and Ebola are passed by feces. The HPV vaccine are causing cancer clusters in young girls.
HIV is a well documented scam. The mRNA virus appears in half the population randomly and is not harmful on its own. AIDS should more properly be called oxidation poisoning. As that was the cause of the initial few cases. The organ failure and death in non oxygen poisoned individuals is caused by the approved treatments. The tests to get you into treatment are entirely subjective.
I am aware of those points, yes. This is why I don't frame my discussion of the Covid vaccines as "they aren't like those other really good ones," "they are leaky, unlike previous vaccines, and thus will have unprecedented effects," etc. All vaccines except maybe Sabin polio are probably net negatives imo.
I'm unvaccinated, so why am I not dead?
Obviously, you'll tell me that COVID really isn't that dangerous to people in my age category; in other words, you'll tell me that nothing the media or government said about COVID was true. Uh, so why should I trust what those same sources are saying about the vaccines?
Literally, your argument is that I should trust the vaccines because I should distrust everything the same sources told me about COVID.
My question, therefore, is were you lying then or are you lying now? Or were you merely stupid then, but now you've figured it out?
Look, the fact that I'm unvaccinated & alive means that SOMETHING you COVIDIOTS told me was wrong, either because you were idiots or because you were lying.
Neither explanation comforts me.
At this point, based solely on the evidence, I have to infer that you either don't know what you're talking about or you do, but you're lying. Either way, I have to presume you're wrong.
At the very least, you need some serious mea culpas here.
Having been wrong about EVERYTHING for 2 years now, a little modesty is in order.
Because just as you're now basically conceding that COVID was NEVER that dangerous, I don't want to be back here in a few years when you have to concede the vaccines were never as safe & effective as you claimed.
Thanks.
You've got to be careful with the UKHSA / SIREN reinfections data -- they specifically excluded BA.1 as being a reinfection candidate (ie, if they had a sample with BA.1 more than 20 days after BA.1 initial infection it was regarded as the test finding remnants of the original infection, not a reinfection). They didn't find much in the way of BA.2 because there wasn't much of it in the country at the time.
This isn't 'proof' -- just shows that it is necessary to do the investigations properly.
OK I see where the Flu report uses variant differentiation for the possible/probable distinction (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1072072/Weekly_Flu_and_COVID-19_report_w17_v2.pdf) but that's for the 90+ day PCR+ reinfection set, it's not clear that it would apply to the VOC analysis. The text of the VOC analysis suggests that there were no censored sequence events. "Preliminary analysis of 496,228 cases of PCR confirmed SARS-CoV-2 infection between 27 December 2021 and 16 January 2022, when Omicron BA.1 was predominant, identified 186,896 BA.1 confirmed cases with genome sequencing. Thirty-one of these cases had another subsequent sequenced sample with an interval of at least 20 days after a previous positive test, with a maximum follow-up period of 72 days."
Thanks, I’ll review the document and add a note. Presumably a censored BA1 reinfection value can be estimated using the BA2 number, which should still show a fairly unconcerning rate
OAS is real and at play.
No, and no.
I’m sick of skimming long articles full of scientific jargon so I’m just going to assume you’re controlled opposition on the payroll of Pfizer. I guess we’ll know for certain once the vaccinated are decimated by OAS this winter.
I’m tired of reading glowing compliments so I’m just going to assume this is another glowing compliment, as to do so can’t present any possible risk of misinterpreting you on a fundamental level. Thanks, that’s very kind!
Have you seen this (just published last week): https://rdcu.be/cLc7b ("SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells")?
From the abstract: "Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory."
It seems to me that these findings further refute the hypothesis of OAS (at least pre-omicron). Just wanted to call it to your attention.
Fantastic - "individuals after breakthrough infection mount vigorous non-spike-specific responses." That's the UKHSA N protein comment blown to bits. N antibodies are higher for the breakthrough set than for naive infected in Ext Fig 1a. Thanks for the tip!
I'm not sure that expanding and differentiating spike memory should be assumed to be a positive (there's always such a thing as overkill), but it's also not a surprising result given Röltgen, et al.'s Fig 4.
I am happy you are giving your opinion, a different opinion than most people on the topic. THIS is good dialog. Much love
Thank you!
Hi Brian,
Long time reader, first time commenter here. I tend to agree with your take on OAS and your theory of innate immune suppression. It jibes with what G.V. Bossche says, plus it jibes with what I've been observing anecdotally. Two things:
1) Have you seen this most recent study out of Germany: https://www.biorxiv.org/content/10.1101/2022.04.01.486695v1. It's entitled "Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation." They found that Omicron post-vaccination infection mediated a robust B-cell recall response, and primarily expanded preformed memory B-cells that recognized epitopes shared broadly by different variants, rather than inducing new B-cells against strictly Omicron-specific epitopes. Wouldn't this study be more evidence that OAS is not what is occurring?
2) Re: spike protein shedding of vaxxed onto unvaxxed. In the past you've discussed this phenomenon. I have observed (and experienced) it anecdotally. In light of our innate immune suppression theory, could it be that the unvaxxed who experience cold-like symptoms after being around the vaxxed are not having a reaction to shed spike protein, but rather are experiencing an innate immune response to omicron itself? If the vaxxed have suppressed innate immune systems, they could be infected (to varying degrees) with omicron but aren't experiencing the mucousal (innate) compartment response (i.e. no symptoms). Thus, the unvaxxed, especially one who had a previous infection and has innate immunity memory intact, would experience an innate immune response after having close/extended contact with an infected vaxxed individual (who is ignorant of it). I could elaborate more, but wanted to run it by you.
Thoughts?
1 - I've seen it, yes! It certainly refutes OAS, though not with a perfect setup. For example comparing 2d+Omicron breakthrough to 2d+1d proves the variant doesn't just "recall" the vax response, though I would like to see results for 2d+pre-Omicron breakthrough for a better comparison. Also it was orchestrated by BioNTech, pretty big conflict of interest haha. Still I'm working on a writeup.
2 - That model is technically plausible. There is someone who employs it frequently, I forget who. For me, I'm a bit skeptical that innate immune suppression would drive asymptomatic-ness, rather than the opposite. Robust innate immunity drives asymptomatic-ness. If the virus is replicating then it is destroying cells and activating inflammatory pathways. So the general dogma that the "immune response causes symptoms" has always struck me as blaming the firemen for the fire.
As for the unvaccinated, they may be in a grey area between innate and adaptive response + small doses of virus, and in that grey area you could model a recurring innate immune stress/training scenario. But... I'm inclined to think that the memory immune system has built-in ways to insinuate into innate immune response even before said response is "overwhelmed." For example lymph nodes are lined with CD169+ macrophages, a very passive immune cell that can culture viruses to promote their growth within the lymph node and make antigen presentation and germinal center formation more likely (https://www.frontiersin.org/articles/10.3389/fimmu.2018.02472/full) - so contra GvB, it does not seem like evolution wants to do everything it can to prevent formation of tailored antibodies to respiratory viruses.
Again, it's still a plausible model. But my guess is that repeat exposure to the virus would tend to generate antibodies in the unvaccinated and then the virus would stop being a bother at low doses.
An alternate model is that exposure to expressed spike would act as a respiratory toxin regardless of antibodies, the same as LPS (organic dust) in constant doses. Toxic stress on respiratory cells could lead to positive feedback loops with the microbiome where you get to dysregulation (bacteria converting to more pathogenic phenotypes, or disruption of bacterial antiviral-immune-promotion - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381240/), and so now even the unvaccinated are more susceptible to colds, or scratchy throat, or who knows what. But I'm not sure if that's convincing. Expressed spike could be more akin to an irritant / allergen unless in super-high doses, who knows.
Thanks for the reply.
1) Agreed. I would like to see results for 0d + Omicron infection or previous infection + Omicron breakthrough. But, they probably wouldn't like those results: that would show natural immunity is more robust. ha ha
2) Agreed. However, what is interesting with the anecdotal evidence I've observed is that the unvaxxed experience cold-like symptoms a few days after or into intense/prolonged exposure to the (triple) vaxxed, yet are not testing positive (e.g. my daughter is a previously infected unvaxxed RN, who in Jan and Feb (when omicron was severe here) would get "sick" the last day of her 3 day shift but would be fine after a few days off, only to repeat the cycle when she returned to work again a week later (and she never tested positive for covid)). Would such a delay in "symptoms" comport with the alternate model you suggested? Or, could such a delay be possibly due to the innate immune system (non adaptive) B cells taking a few days to produce new/more IgM abs in response to the re-infection? From what I understand, these IgM abs are short-lived and would disappear once the infection is cleared (and theoretically would re-appear when an omicron antigen is once again detected in the nasal or throat passage).
Interesting things to contemplate.
Actually, that setup is partly contained in the Austria Omicron study (https://unglossed.substack.com/p/the-austria-omicron-study). Here the small sample size seems to drive unexpected results, but either way it also refutes OAS. Both injection and previous infection outperform the naive group in post-Omicron anti-Omicron-neutralization.
2 - Yes, that would fit in a "spike as toxin" model if the part about toxicity->microbiome dysregulation->downregulation of antiviral (or even anti-fungal) innate immunity turned out to be the perfect solution. After exposure to the spike goes away it takes a few days for inflammation to settle down and microbiome promotion of tissue repair to turn back on. But once again the "innate stressor" model also works, it's just that I tend to think adaptive immunity would kick in in that case. Essentially my instinct is that adaptive immunity / antibodies are designed to give the innate immune system a rest from the virus-of-the-season for exactly this reason, you don't want to stress it long term.
You may be right about IgM, my understanding was that the mechanism of generating IgM is not well understood but that could be a gap in research on my part. Note that natural IgM also participates in directing antigens to germinal centers (https://www.jimmunol.org/content/jimmunol/194/1/13.full.pdf) which again implies that evolution wants the adaptive immune system to insinuate into innate antiviral response as much as possible.
1. Right! I remembered that study shortly after I replied. [BTW, you're analysis of it was excellent!]
2. Thanks for the followup explanation. I guess the whole phenomena can be put into the "who really knows??" category. FWIW, I have not observed that phenomena since March 1--round about the time omicron cases radically dropped off here in Ohio AND/OR three months after most Ohioans got their booster (although only 30% got boostered). So, my anecdotal evidence could support both models: either a) the vaxxed finally cleared the virus and are not re-infecting others, including the unvaxxed (the "innate stressor" model); or b) with the booster waning, the spike proteins levels in the vaxxed have significantly dropped (the "spike as toxin" model).
Notwithstanding the cause of said phenomena, there is something we've both touched on that I think needs to be explored (and also ties back into your original post): the role of IgM and (mucousal) Secretory IgA (SIga) abs in the innate immune system. Is it possible those abs are being suppressed in the vaxxed (which is causing the issue in the UK right now)?
It is my understanding that both are part of the innate immune system--they are not custom-made abs in response to a specific antigen (and therefore are not considered adaptive), but rather show polyspecificity (i.e. they weakly bind to to a large variety of epitopes in a variety different antigens).
Studies have shown that the vaccines produce little (if any) SIgA abs. Is this (partly) why they are getting (re-)infected? And, could it be that their B1 cells are not expressing/secreting IgM abs (which you explained here: https://unglossed.substack.com/p/neg?s=r), so that their first line of defense against omicron has been effectively disarmed?
The "my take at GvB's nAb theory" model in Neg proposed that residual leaked IgG (circulatory IgG leaks passively from plasma to mucosa, which is why the injection produce short-term infection efficacy when plasma IgG is really high) was outcompeting nAbs and thus leaving innate cellular immunity in the dark. This doesn't really fly since it turns out IgG cross-engages with innate immune cells; so there shouldn't be any point during IgG fadeout where you get to negative efficacy via out-competition. So, pending more research, I'm hewing to the KISS model of innate immune suppression: the vaccine just makes recipients unhealthy. It wears down their bodies and exhausts their immune systems. Same as the party lifestyle of the original 80s AIDS crowd.
And that KISS model may be correct.
A little anecdote which may support your KISS model:
Prior to a third (booster) jab in mid-December, a friend (who is fit & healthy; rarely sick) had a WBC of 7.67 and a lymphocyte count of 1.69. In mid-March, those numbers increased to 10.3 and 2.8, respectively. Other than a week of cold-like symptoms (perhaps a mild bout with BA1 or some other cold) in early February, there was no appearance of any infection or sickness (i.e. asymptomatic) at the time of the CBC test in March. While 10.3 and 2.8 are not high enough to be in the leukocytosisis and lymphocytosis categories, they are on the high end, indicating (to me) that the immune system is fighting some sort of infection (even though there are no symptoms of infection).
Could this be a signal of the body getting worn down and immune system getting exhausted? Makes me wonder.
So leaving all the acronyms aside, what do you project might happen if people got a measles vaccine every three months for a couple of years? Would the immune system stop recognizing measles as a threat? Maybe see it as part of the larger organism? Then what might happen if there were a slight mutation to the virus...nothing too obvious to the immune system but enough to make a significant impact to the organism?
Artificially induced immune tolerance is largely a theoretical subject, so all I can do is theorize. But I would bet on very little long term immune impact. Essentially the immune system at the end of the two-year course would be the same place as if it had received just a single dose close to the end of the same two year period (and didn't encounter the virus in the wild in the meantime). For the young there would be some long-lived memory B Cells that will last forever, and a short-term high antibody level that will fade out over time regardless of how many shots one had before the end of the course.
Essentially what I would assume is that during each boost, the previous memory B Cells and antibodies continue to be such a good match that no new immune response is generated. When existing IgG antibodies are a good match for a circulating antigen, it outcompetes IgM, preventing the antigen+IgM+C3 complex which activates the "switch" that tells B Cells to traffic the antigen to germinal centers FDCs to say "hey make a better immune response to this." So the re-injected Measles antigens are handled by the previous immune program and things don't devolve back to the executive level (antigen presenting cells and germinal centers) where a new immune response can be formed. Likewise, since the gut microbiome isn't involved, there's little risk of inducing tolerance. On the other hand, a little bit of "spillover" into novel executive-directed immune response leading to autoimmunity for some recipients, sure, maybe; and there could be direct autoimmunity from constant high anti-measles antibodies leading to immune response against whatever self-proteins they resemble, etc. So that's there, but I wouldn't rate it as likely a universal danger.
An mRNA / DNA measles vax might be different, because maybe it would be cells in the GI tract that express the proteins, maybe that could cause some cross-wiring and tolerance, who knows. And so same for the Covid vaccine boosters, maybe there is a good risk of tolerance. But for an "inactivated" virus vaccine, I wouldn't bet on it.
So a difference between a sterile and living vaccine? I also wonder about chemotherapy. It often works very well at first but after time tolerance occurs and the mutated cells no longer respond (by dying) and in fact may even accelerate replication. Adaptation and tolerance seems to be a response to all kind of organisms vs molecules. (antibiotics) not beneficial. I know I am rambling but trying to understand the difference here.
A little bit. A "live" vaccine is really just a functional virus. I also misspoke because the Measles vax isn't "inactivated," just super-attenuated and a bit cell-culture-evolved (it targets slightly different receptors than the wild type). But at the same time, "inactivated" is just a euphemism for chemically treated (and possibly still infectious), so all you can really say in general is that you don't want something that is injected into the blood to have too much kick.
Whereas the main vaccine we would think of as a "live attenuated" is the Sabin polio, which is delivered to the GI tract so it pretty much mimics natural polio infection. Sorry for muddying that up, I should have just used "whole" injected virus.
The distinction I really meant to draw is that the mRNA vaccines don't "wear" their own antigen, so anti-spike antibodies don't prevent the LNPs from getting into cells and making the cells produce more spike. This might lead to tolerance or autoimmunity for a variety of reasons. But a "whole" injected virus wears the antigen, and so when it is reinjected, antibodies block it from entering cells. Memory B Cells ramp up even more antibodies, but there's no or very little "new" immune response.
While I agree with most of your concerns about the validity of the N seropositivity data (it would be better to get a more explicitly uniform sample), I would also point out that the higher seropositivity by age tracks very well with the lower vaccine uptake by age. For example, the 17-30 age group is probably around 65% vaxed, and the uptake has risen fairly recently - so the lower uptake combined with the odds that they were infected prior to vax would seem to comport with the data on N positivity. At this point, as it appears that 10% of the UK population seem to have C19 at any given time, isn't it surprising that N positivity still remains down under 40%?
As for why UK seems worse than New England - I think the high vax rates in New England are biased along socioeconomic lines - in the highest density areas, higher likelihood of vax corresponds with higher likelihood of remote work. In my workplace it's got to be close to 99% (myself being the only refusenik I'm aware of) and the office is probably 20% occupancy on a busy day. These people don't live in the denser areas - and most of the poor folk who do already got infected last year, and are on balance less likely to take the vax (hey - they aren't overeducated idiots after all!)
The UK is overall 3.5x more densely populated than New England, and NE may have a bias in vax uptake to more wealthy suburban, zoom class populations. Some other differences include UK having a more homogenous population, substantially higher latitude, and a different mix of vax types, with higher prevalence of Astrazenica. I would also point out that while less dramatic, the Mass. new case rate has not hit 0 since July 2021, the lowest new case rate since then has been 30/100K after Omicron swept through. So basically the problem does exist there too.
Your point about the network effect is very important. I think this is also an important factor in your disagreement with the "worry window" concept. You point out that the worry window / immune suppression is a small effect. This is true. But it does exist - and I submit that this small effect, when combined with the network effect, leads rollouts to create outbreaks. This produces the very obvious signal in the data that people latch onto, and sometimes then want to over-estimate the actual effect of the immune suppression.
BTW have you read this: https://rwmalonemd.substack.com/p/when-is-mrna-not-really-mrna?s=r
it was a good intro to the impact of pseudouridine which I found very enlightening. I still need to read the source papers to understand it more fully. One thing I remain puzzled about though - the effect described here seems like an intra-cellular effect as a result of the transfection - so once those cells get killed off in the immune response, why would this effect persist for longer? Maybe the answer is, it doesn't persist. But then why do we seem to continue to see signs of long term immune suppression? Psuedouridine does not seem to explain the whole story here.
So, that goes back to part i of the original UKHSA comment in October, which is the part that correctly explained the trend - the donor sample is not reflective of real world vax rate. Donors are “do our bit” types. Note that overall S seropositivity is already near-100% by mid-2021. So there were almost no unvaxxed donors after mid-2021 and so the low N-rate would appear to be a portrait of what is happening to the vaxxed (when in fact it is only what is happening to the infection-negative vaxxed). Likewise, there are no apparent dips in S seropositivity in the last months so the upswing isn’t a result of any dirty, selfish unvaxxed reentering the donor pool. Now for the youngest group almost half of (vaxxed) donors are N-positive. Besides residual selection bias there’s probably also antibody fadeout (whereas S seropositivity is propped up by boosting even among the not-recently-infected), and a lot depends on whether the “positive” threshold for both assays is equally sensitive.
Yes, I agree with all of those points about New England, and have noticed the MA persistency but hesitate to rule out a testing artifact given that NY isn’t in agreement.
As for worry window, the converse Network Effect interaction is that swings in innate/adaptive immunity are happening all the time, in fact that is a plausible mechanism for explaining seasonality. So if you send a ripple through the network when innate/adaptive immunity is rising (as at the end of a wave), you don’t make a difference, and likewise if you send a ripple at the beginning of a wave (the wave was going to happen anyway). And the “window” is a ripple by definition since it is short. You would have to introduce the ripple into a equipoised system to make a difference, and in reality there is no equipoise, only equilibrium. Besides that, the evidence for the ripple itself isn’t even strong, imo.
Right, I think the pseudouridine doesn’t explain persistent effect and the “60 day mystery” solves why it is detected in germinal centers. So we can assume a short half-life. Long term effects, including immune suppression, are probably a lot less elaborate in mechanism. Ok, you’ve got endothelial inflammation, fibrosis here and there, long-term metabolic dysfunction - so the immune system is worn down. Same as for long-term drug use in the 80s leading to AIDS when combined with network effect (and spilling over to non-users in the same network once the critical mass was reached).
Hi Brian. I just woke up (will go back to sleep asap) and saw your article! Love the controversy and your, as always, politely stated and carefully argued opinion.
This is what the debate should always be, as opposed to abuse or attempts to "cancel" their opponents.
That said, you make two statements:
1) OAS is not real
2) The UK's endless Covid is "immune suppression" driven, saying that there is a network of immune suppressed persons, that is big enough to drive a wave of endless cases.
I want to leave 1) aside for now because I need to go back to sleep.
However, regarding 2), you are likely to be completely right and spot-on in identifying ANOTHER problem in the UK: a critical mass of generally immune suppressed people having colds from hell, endless covids, and soon everything else, and endlessly infecting each other.
It is not just the UK's (or "the isles") problem. In Germany, the endless covid is even worse than in the UK, or perhaps the Germans do more tests, but clearly Germany has a endless covid problem also. Israel's graph of cases this year is similar to UK's. The only no-longer-important difference between UK and Israel is last November.
The US seems to be the exception. It may be so because the US is especially bad at keeping national statistics, but it could also be for other important reasons. We'll explore it later.
The bottom line is your immune suppression story is not something I am objecting to, and in fact I support it 100%. There is immune suppression indeed and we are seeing it. After three vax doses and three covids, the immune systems of such unlucky people will likely be severely suppressed, which is kind of what I kept on saying and screaming about too comparing Covid with AIDS.
Not sure how many spike protein transfections (vax or Covid illness) is enough to cause immune suppression, it could depend on luck of specific persons, but clearly, the more the worse, and the effect is cumulative, leaving people worse off after every episode.
We have a health emergency that is likely real and likely will end up badly, and we need to warn as many people as we can about it.
More about OAS later.
The ability of chronic stress to undermine the innate immune system could be a factor. There have been studies on this in students showing those under stress are more susceptible to colds (I think it was somebody called Cohen who did this research). What have we been subjected to over the last 2 years? Fear! Fear of the virus, fear of being forced to get injections, fear of loss jobs etc. The population has been chronically stressed for the last 2 years. I can attest to my own health, which is by no means bad, still being worse since this pandemic kicked off despite not being vaccinated nor testing positive for COVID. I just seem to get minor infections whereas I didn't used to do. hardly at all. This is despite taking active measures, more so than I have ever done before, to bolster my immune system with supplements etc.
Thanks - actually, I wasn’t sure whether I should add repeat-dosing to the theory. It may be the case that the UK would be in the same boat if everyone stopped at 1 dose, or at least there may be “diminishing negative returns” on the later injections. It remains good advice to stop the injections ASAP either way! However, using the building analogy, the only solution (if there really is an emergency of innate immune deficiency going on in the UK and now maybe West Europe) besides getting out of the building is for everyone to try to improve their innate immunity. Doubt either thing will ever happen.
Good catch RE Israel - I hadn’t looked at cases there in a week or so. I might have to fix my text.
Thank you, I really appreciate it when substackers give a different views from one another. It keeps my mind open, and we all get better information. 👍🏽💕
Thanks!
There's a lot to say about the constant re-iteration of OAS. Just like I have said previous (and you have mentioned) it's like those ardent supporters of OAS are stuck within their own proverbial OAS. It just feels like something I've been increasingly concerned about where it feels like people are collecting information but generalizing further than they are allowed based on the evidence presented. It also doesn't quite make sense why OAS keeps being used to argue the immunological effects of targeting a completely different antigen.
One thing for people to keep in mind is that the concept of the N line being flat is "relative" and is likely affected by the scaling to accommodate the S curve- if you compare it from the start of measures you can see that it doubles.
The higher increase within the younger demographics is also to be reflective of older people being vaccinated first and the younger group not having it available for several months. All this suggests to me that, because the N protein is sequestered within the virus, it may be that the host is not experience the full exposure of the virus' antigens such that the anti-S spike may be removing the virus before the N protein can make itself known.
And quite frankly, I'm getting rather tired of the seeing this large dependency on case numbers. I thought many people have, rightfully, criticized the veracity and accuracy of these tests. Why do these people then rely so much on this as evidence for their narrative or ideas? Either PCR tests are faulty and we don't rely on them or they are accurate and we can trust their results. They can't have it both ways.
As noted in my reply to Jon, I’m usually careful that the case trends I discuss are of decent fidelity but leave out discussion of my methods here since it would be tedious for the reader. Besides that, I’ve actually been pretty bullish on PCR+ as a proxy for viral challenge since July, so there’s no “having it both ways” in Unglossed World, haha. I am provisionally not as sure if the same proxy is as valid for the Omicron siblings as for the Wuhan strains, however.
Right, lack of N antibody wouldn’t be OAS or even necessarily suggestive of a deficient post-breakthrough immune response anyway. Is N antibody even functional, or just a correlate for broader immune recognition? If the latter, then the correlate may simply turn out not to be as valid for the breakthrough immune response. All that matters is reinfection and afaik the best view of what’s going on there is still Goldberg, et al. - https://unglossed.substack.com/p/darmok-and-the-spike-protein-at-tanagra?s=w#footnote-8 - there is only a truly tiny increase in reinfections which can be attributed to the early breakthrough “mildness discount.”
Many of my grievances are not in your direction Brian as I can trust that you engage in a lot of sourcing and critical thinking! But it's more of the fact that even to this day it appears that case rates are still being plastered all over the place. If it's being used to validate the ineffectiveness of these vaccines then at this point that becomes redundant since that was figured out months ago. Are the same people who continue to utilize case rates the same people who have been critical of the accuracy of these tests? In which case I question why this double standard is occurring.
Right, you can notice that tension in a lot of the worry window / negative efficacy theorizing for example. One minute the injections are responsible for any and every upswing in cases, the next minute "severe efficacy" is a secret illusion created by the fact that the vaxxed "get severe Covid" without testing positive. Ok... sure...
Yupp, it's making me consider writing about this and opening up discussion. I guess it bothers me because it introduces a lot of noise into the discussion and clouds my ability to assess things properly. I just wish more people were consistent.
I've been thinking the same thing, that case rates cannot be counted on for accurate info.
It's definitely the reason I don't ascribe to the "endless COVID" argument. If the intent is to gauge endless COVID based on PCR positivity then we would need to trace PCR tests back to an adequate number of people, see their positivity rates, see their severity of illness, and see their immune response. There's a lot more to it than just reading case rate graphs, and considering so many people have been critical about them in the first place I have to wonder why people have jumped onto them now.
I used to do PCR testing for COVID and my argument has usually been that it's OK for symptomatic people but in no ways should have been used for widespread testing and especially for asymptomatic people. I've been very critical of the mass testing and like you said greater testing means more incidences of false positive. This also really muddied the waters for what constitutes "Asymptomatic"- over 40% of people being asymptomatic seems more like the inclusion of a lot of noise rather than actual signals.
And like you said PCR tests have always been confirmatory, not diagnostic, which is also the biggest issue again with PCR it should not be used as the only assessment for positivity.
Right, I’m usually running envelope-math validations of any case trends I talk about at this point, and just not mentioning case trends that appear to be in false positive territory if I don’t have to. It would be very tedious to show my work here, but the gist is that unless the per-test positivity rate goes down than a corresponding upswing in cases is not an artifact of increased testing + false positives.
Right, and one reason for “walking away” from the UK stats was the possibility that it’s a test behavior artifact, despite the solid positivity rates since summer (which were solid despite rampant school testing). Here again the change in West Europe argues for taking the UK stats just a bit more seriously again. Ironically, at the same time they have just ended free testing for low risk groups so the forever wave will possibly die out anyway.
Echoing ForkInSocket, the pre-summer trend was that waves went to zero (though there was still a double wave in autumn/winter 2020 so I think we can grant double-waves as the geographic norm (some kind of effect of the UK’s super-suburban layout, combined again with lower baseline innate immunity than continental Europe); and then the spring 2021 lull was propped up by the happy valley of infection efficacy, and since July they’ve been living in the “infection purgatory.”
However, I want to be careful that the evidence is both circumstantial and heterogenous. The SARS-CoV-2 case rates don’t tell us how many “colds” people are getting, just the anecdotes. So explaining the case rates with innate immunity can’t rule out other factors; it’s just the one that’s consistent with the anecdotes.
But, the earlier waves there went back down to 0. Right up until the vax rollout..