Hey look, serotypes!

I have to point this out. About half a year ago, I said that you’re probably going to end up with SARS2 serotypes, simply because it was unlikely by now that something new that emerges would be superior enough to completely eradicate the XBB lineages. Immunity would first be reoriented against the new serotype and that would then create a landscape within which the old serotype could re-emerge.

Well guess what happened. It turns out there’s an XBB lineage with a weird insertion at 212 that emerged in Canada and spread around the globe. So now you have two versions of the virus, both with insertions in different parts of the NTD. They’re both going to be under pressure to change the NTD in different ways. For JN.1 it’s straightforward to start deleting stuff around the first loop, due to the insertion at 16. We see it happening in multiple JN.1 lineages, a deletion at 31, just after the first immunogenic loop and a bit after the insertion, that allows a new glycan to be added at 30. But this XBB variant would have more of an incentive to delete chunks further along in the NTD.

Remember, it’s when deletions and new glycans emerge in the NTD, that the last antibodies that neutralize the virus in most of the population are going to fail. You will end up with very fusogenic variants, that spread by moving from one cell into another, without ever being in reach of the antibodies. The antibody response against the RBD is already pretty much useless by now.

The important thing to keep in mind is that once you have multiple of these highly fusogenic serotypes circulating in the population, you can’t vaccinate anymore. Most of the population already has high concentrations of antibodies, vaccination under these conditions won’t improve the population’s protection, it will merely favor one serotype at the cost of the other. By now it’s clear that the BA.2.86* Spike doesn’t do a clean sweep: It stays stuck around 93%, so it doesn’t completely wipe out the other lineages.

There are probably other serotypes out there too, we just don’t see them because sequencing is down by 99%. There’s a weird one in France, but nobody knows how widespread it is. There’s also a derivative of the original Omicron still circulating in Nebraska, infecting multiple people.

I know you’ve probably seen it argued there will be some sudden new doomsday variant this summer that leads to overnight vaccine failure. I don’t think this is likely, although it is inherently impossible to rule out.

In the coming weeks we can expect S:R346T, S:F456L, S:S31del to grow globally dominant.

Right now, adding the whole thing together suggests a 117% growth advantage.

What seems far more likely to me unfortunately, is that we’re gradually going to see different serotypes emerge: XBB lineages and BA.2.86 lineages, along with lineages based on whatever else is still out there.

Those lineages will undergo deletions in the immunogenic loops of the N-Terminal Domain, facilitated by the rare insertions they tend to develop in the NTD. These deletions will increase fusogenicity and thereby increase the intrinsic virulence of the virus.

That ultimately results in a virus that behaves more like the original SARS.

The reason this is happening

So why did this happen? Well, allow me to show you something.

There is a notable difference by now between vaccinated and unvaccinated people, in regards to the regions their T cell receptors look for. This has been studied, in people who were infected in the first half of 2022.

Among the unvaccinated, they found strong overrepresentation of the S673-699 epitope. On the other hand, among the vaccinated, they found strong overrepresentation of these four regions:

S135-177, S264-276, S319-350, and S448-472.

The first of these four is easy to understand: It’s the N3 loop of the NTD. The other three regions are also in the NTD, but don’t correspond neatly to any of the known immunogenic loops.

But here’s the whole picture, which tells the story in my opinion:

I would argue it’s pretty obvious what’s going on here. The unvaccinated adaptive immune response tends to focus on regions in S2. The vaccinated adaptive immune response tends to focus on the N-Terminal Domain. We also see it strongly preferentially focuses on the region around 180, which is an infection enhancing site. The N5 loop also seems to be preferred.

So it seems straightforward, to expect that the NTD is going to undergo radical changes now, now that antibodies against the RBD have become useless. As the loops in the NTD grow shorter, by deletion mutations, you end up with a virus that behaves more like SARS1.

The entire Spike protein is covered by glycans, with the exception of the receptor binding domain. But now that the RBD evades the antibodies, we’re reaching the point where the antibody response depends on those last few regions of the NTD not covered by glycans, where antibodies can still bind to neutralize viral particles.

You also have to keep in mind: As more and more of the Spike protein becomes inaccessible to the T-cells, whether due to evolution to resemble our own proteins, deletions, steric hindrance, or glycans that are added, you’re going to see people’s lungs populated by an increasingly homogeneous population of T-cells.

With every breakthrough infection, the immunological abnormalities further escalate. That’s why you now see a very different antibody response against JN.1, when comparing vaccinated and unvaccinated people, as the vaccinated keep recalling antibodies against recessive epitopes in the NTD. This is what leads to the current situation, in which people suffer constantly elevated levels of respiratory disease. A lung environment populated with T cells looking for SARS2 has little room for other T cells looking for unrelated respiratory pathogens.

Through vaccination, you put abnormal antibody pressure on the Spike protein. This abnormal antibody pressure leads to affinity escape (escaping low affinity antibodies by increasing ACE2 affinity). But now that the abnormal antibody pressure is so strongly concentrated on the NTD, you’re encouraging the immunogenic loops of the NTD to grow shorter, which is known to dramatically increase fusogenicity. In other words, you are selecting more virulent variants.

It’s very simple: You want to see a small number of high affinity antibodies, against select regions of the Spike protein, in people who suffered severe infections. Those antibodies will be against regions that are associated with virulence. As a result, people will gradually offer a selective advantage to variants of this virus that are less virulent. What you don’t want to see, is this yellow line in the whole population:

This is what happened to the four hCovs in our species: We had a pandemic long ago (including one in the 19th century), a bunch of people died, then it gradually grew less virulent. But here’s what’s happening to SARS2:

It has been gradually growing more virulent since the first Omicron, but we don’t really notice it yet, as the most vulnerable people have already died by now. This happens, because the population is unable to select against virulence, because there is an antibody response against regions of the Spike protein that would normally not be targeted.

The previous failed vaccination experiment

I think this is just genuinely going to escalate dramatically.

Why?

Well, we can look at the attempt to vaccinate chickens against influenza in Asia. These vaccines began selecting new variants, they ended up breeding versions of influenza that are extremely deadly and focus on infecting the brain rather than the lungs. Those versions have now spread around the world and killed millions of wild birds, entire species have had more than half their population die in a single season.

SARS2 is happily proceeding along the same path, with vaccine resistant versions emerging that are getting better at infecting the brain and increasingly competent at fusing cells together. In both cases we’re dealing with a virus that has an abnormal polybasic cleavage site, allowing it to infect endothelial cells.

If we’ve tried the exact same experiment of vaccinating against rapidly mutating respiratory viruses in another species and ended up breeding deadly viruses that decimate wild bird populations, wouldn’t you expect that performing the same experiment in our own species also results in deadly viruses that decimate our population?

You might argue to me that people now have immunity against proteins other than Spike too. But I don’t think it’s going to be very relevant, because you can only neutralize viral particles through Spike.

Immunity from interfering defective viral particles

So what about the unvaccinated? Well, I have explained most of the puzzle a few times.

But there’s one element I’ve never addressed: interfering defective viral particles. This is not difficult to understand. When a cell is infected with the virus and does not get killed, but tries to get rid of the virus on its own, it will contain defective viral proteins or viral RNA. When it then gets infected again later on with a new variant, it will produce defective viral particles, that stimulate the immune system without being able to complete the viral cycle. These defective particles interfere in the normal particles replicating.

NK cells are aggressive upon a first infection, destroying infected cells. Upon subsequent infections however, they tend to prefer telling infected cells to solve the problem themselves. They have receptors they can use, to detect large chunks of weird RNA, which they will then delete. This means you end up with some persistent broken RNA in those cells, only activated again upon reinfection.

That’s a normal part of how immunity is supposed to work. It has a small protective effect on unrelated viruses, but a major protective effect on closely related viruses. Once you vaccinate people, you tend to break this immune mechanism, as the cells capable of producing defective viral particles will get killed.

Once you make the antibodies and T cells do the job of dealing with this virus, you set the immune system up for failure, relying entirely on these two mechanisms that are very vulnerable to the effects of mutations to the Spike protein. Such failure could come very suddenly and unpredictably, as changes to cysteine bridges can cause the whole NTD to fold differently, thereby evading most antibodies.

So all these studies, arguing that the virus never leaves your body, are not discovering something shocking. They’re just discovering how the immune system works: It encourages infected cells to store broken genetic material of viruses, that interferes with their replication next time the virus shows up.

Sometimes this means the virus fails to spread in your own body, sometimes it means you pass on versions of a virus with reduced fitness. Vaccinate everyone with inactivated vaccines and you break this mechanism.

Solving the problem

The tragedy is that the immune reprogramming after vaccination is effectively permanent, it is merely recalled with every subsequent infection. The antibodies that bind to new versions of the Spike protein prohibit NK cells and other elements of the innate immune system from learning to properly do their job during subsequent infections. You can look at the antibody response to the newest JN.1 strain here:

Adults with two shots of mRNA:

Unvaccinated adults:

The immune system is still stuck with an abnormally elevated antibody response to this virus. As a result, the virus continues to be under pressure to shorten its immunogenic NTD loops and increase its fusogenicity.

In contrast, the innate immune system will have to do the job among unvaccinated adults. These are mechanisms that select against virulence.

The situation we’re dealing with, is one where the intrinsic virulence of this virus will continue to rise, until the antibody pressure exerted by the vaccinated is diminished.

Everything I’m saying here is a natural outgrowth of how the immune system works.

The main purpose of antibodies is to exert selection against virulence associated epitopes. That’s why survivors of the 1918 influenza pandemic have antibodies that react with the 1918 pandemic, but not with modern influenza strains. These people who built up natural immunity, with antibodies against select virulence-associated epitopes, are the reason the 1918 strain of influenza was replaced over time by more benign strains: Their immune systems would only pass on more benign versions of influenza.

We broke that mechanism for our own short-term self-interest and made a handful of people billionaires in the process.

36 Comments

  1. Thanks for another update, I’ll leave a more detailed comment later on today when I have more time, but for now, with regards to the following quote:

    “So all these studies, arguing that the virus never leaves your body, are not discovering something shocking. They’re just discovering how the immune system works: It encourages infected cells to store broken genetic material of viruses, that interferes with their replication next time the virus shows up.”

    This is a relief. I remember Kareninca was referencing a doctor (sorry can’t remember his name) who was claiming that there were viral reservoirs in the bodies of not just the vaccinated (which would make sense considering that IgG4 antibodies encourage chronic/persistent infections) BUT ALSO IN THE UNVACCINATED.

    So hopefully this “interfering defective viral particles” phenomenon/mechanism that you described debunks the claims of that doctor.

    • Oh I’m sure there are unvaccinated people with persistent infections. A persistent infection is just an infection that lasts for a long time. But it’s a rapidly mutating RNA virus. Within any single individual, it rapidly loses fitness. It rapidly tends to lose its furin cleavage site for example, without person-to-person transmission.

      Eventually, unless you’re severely immunocompromised (in which case you have more pressing concerns), such persistent infections decay into defective interfering viral particles, that are only activated during a reinfection.

      If we had not vaccinated and had not practiced social distancing, we would have seen this phenomenon take place on a global scale: A gradual decay in the intrinsic fitness of the virus, as chunks of RNA are irreversibly lost, the signal drowning in the noise.

      After all, MERS and SARS1 don’t just keep spreading around the globe forever either.

      • > But it’s a rapidly mutating RNA virus. Within any single individual, it rapidly loses fitness.

        This is closely related to the subject of my next comment.

        I am interested in learning more about this phenomenon where chronic/persistent infections suddenly take a turn for the worse. You’ve used the example of feline coronavirus transitioning to feline infectious peritonitis in cats.

        Similarly, you’ve worryingly predicted that we will see more and more instances of persistent COVID infections within a host which will eventually cause deletions in the three immunogenic loops of the N-Terminal Domain, which will dramatically increase virulence through improved fusogenicity. So, variants that will be very good at spreading WITHIN a host, at the cost of being relatively poorly transmissible between different hosts. Dr. Geert Vanden Bossche has published similar predictions:

        “This progression inevitably culminates in a final stage where the immune pressure on the virus’s capacity to propagate and survive rises to an extent that it is compelled to spread massively within the host rather than from one host to another. I have no doubt that this evolution will result in a rapid dissemination of the virus from the upper respiratory tract to all organs, leading to swift and extensive mortality in these populations.”

        https://voiceforscienceandsolidarity.substack.com/p/how-will-the-ongoing-immune-escape

        And you yourself wrote last August (“BA.2.86: The next Serotype”):

        “In a chronic infection, a virus can develop mutations that help it to survive in your body, at the cost of its ability to spread through the air, pass through the mucous membranes and infect another person.”

        “BA.2.86 doesn’t have a lot of new threonine and serine mutations that would enable complete antibody evasion. However, it may be very good at establishing persistent infections, that eventually lead to such mutations that cover the Spike protein in sugar molecules and make the antibodies powerless.”

        And you have also described a third mechanism of complete antibody evasion, where cysteine bridges change the shape of the entire protein.

        So, with regards to these three potential mechanisms of complete antibody evasion in the vaccinated (NTD deletions, spike glycosylation and cysteine bridges), my question is:

        Just how common will these 3 mechanisms be observed in the vaccinated segment of the population? I mean, if in a years time we have variants that are REALLY GOOD at establishing persistant infections, you’re saying that the antibody selection pressure on these viral regions will be SO STRONG that this will be very commonly observed? It’s really plausible and consistent with evolutionary theory?

        • Just some additional clarification to try and make my comment more clear:

          If we define the classical Darwinian view of evolution as:

          – Random mutations are occurring (as always)

          – Specific mutations that offer a fitness advantage will be selected for

          So of course it seems inevitable that some of or all 3 mechanisms described above will eventually happen (as you described in those hospitalised patients in South Africa) due to there being billions of ‘Petri dishes’ all around the world incubating such mutated variants.

          But I’m still somewhat struggling to understand that we will see these variants arise on a WIDE SCALE in huge swathes of the population. You and Geert are saying that once the immune pressure rises to an extremely high level it is inevitable that this will happen?

    • I think that nearly everyone who has caught covid has reservoirs of multiplying virus in the brain and in the gut and in the bone marrow. Not just bits of virus, but actual replicating virus that is presently being kept under control by the immune system, but eventually won’t be. Prove me wrong. Or rather, prove Daniel Brittain Dugger wrong, since I am a midwit and have trouble understanding how it is possible to distinguish between the presence of viral bits and the presence of replicating virus (especially when the virus is under control). Anyway, here is a good popular press article: https://www.wsws.org/en/articles/2023/09/12/vbai-s12.html. It links to the Nature Immunology article that it is based on.

  2. Awesome. Could we get your take on the lab leak vs. zoonotic origin? I was leaning toward lab leak, but am now not sure given that SARS-CoV-2 apparently does not carry the hallmarks of recombinant DNA technologies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117112/. And On the other hand can you really anything produced by JHU? But Astral Codex Ten has also dismissed the lab leak hypothesis: https://www.astralcodexten.com/p/practically-a-book-review-rootclaim. Yet, I would have thought that it is prima facie suspicious that SARS-COV-2 was immediately so infectious to humans? But hey, what do I know – I’m just an unvaccinated tin foil hat wearing conspiracy theorist after all.

    • Of course it leaked from a lab. That’s why the lab shut down, that’s why they removed their database from the Internet.

      It was passed through humanized mice, before eventually being set loose. We know this from the 6 and 7 amino acid length peptides, which resemble only mice and human proteins. You can just tell by looking at the sequence.

      What most likely seems to have happened is that the cage within which the humanized mice were held had some defect that led to researchers being exposed to the virus. I quote:

      https://www.propublica.org/article/senate-report-covid-19-origin-wuhan-lab

      On Dec. 11, a team of WIV researchers submitted a patent application in China for a device to filter and contain hazardous gases inside a biological chamber, like the ones it used to transport infected animals. The application, which Vanity Fair and ProPublica reviewed, noted that defective air hoses on animal carriers can lead to “multi-stage” risks when airborne pathogens are involved, and warned that a “stable high-efficiency filtering device” and corrosion-resistant frame were “urgently needed.” The following year, in November 2020, the WIV applied for a patent for a new disinfectant compound that it argued would reduce “the corrosion effect to metal, especially stainless steel material,” the interim report says.

      The patent application, which listed seven inventors, including Yuan Zhiming, vividly describes concerns related to its prior disinfectant:

      Long-term use will lead to corrosion of metal components such as stainless steel, thereby reducing the protection of … facilities and equipment. It can not only shorten its service life and cause economic losses, but also lead to the escape of highly pathogenic microorganisms into the external environment of the laboratory, resulting in loss of life and property and serious social problems.

      In the words of one China analyst who serves as an adviser to Western companies, when Chinese officials “describe the solution to a problem, that’s how you find out what went wrong.”

      That’s what the documents suggest happened. It’s extremely banal, but it is what it is.

      They toyed with things they should not have toyed with. They should have never produced rodents with humanized lungs and they should have absolutely never infected them with SARS viruses. It’s something so stupid, it was bound to go wrong.

      Anyone who tells you it emerged naturally is a dishonest actor.

  3. Thanks for simplifying not so easy to comprehend science.

    I am curious on your take for the mRNA injections they are creating for cancers. Do you think the original mRNA injections taken by those with cancer will help or hurt the antigens they are producing for the various cancer types?

    • When you develop cancer, your own immune system has to fight the cancer. In the vast majority of cases, it succeeds at that quite well, so you never find out you had (pre)cancerous cells. Some cancers are kept under control so long that you actually die of something else (commonly seen with prostate cancer).

      Sometimes you’ll need autoantibodies, antibodies targeting your own proteins, to tag these cancerous cells so your immune system knows they need to be killed.

      The problem is that IgG4 antibodies don’t instruct the immune system to kill a cell when they bind to it. In fact it’s even worse than that, they interfere with other antibodies binding to those same cell, they stop those other antibodies from properly instructing the immune system to kill a cell.

      So that’s basically the main reason why there’s a worry that the IgG4 antibody response seen after mRNA vaccination could result in rapidly progressing cancer.

      I know there are more esoteric mechanisms proposed as well, but this to me seems the main concern.

      How big of a problem this is would need to be studied. But studying it would first require acknowledging that something went wrong and we’re still stuck trying to get the system to acknowledge that simple fact.

      • Most waxxxxine turbo-cancers are DNA mismatch cancers.

        Easy to see why.

        Look at the 4 x sales increase of immunotherapy drugs like Keytruda.

  4. If your scenario is true (and it seems a lot more plausible to me than Geert’s hivicron doom) then the medical community is going to come up with a 4-in-1 mRNA supervax targeting the 4 circulating known serotypes, right?
    Which I suppose will lead to further immune escape and more serotypes.

    We never should have gotten on this treadmill. I had a very bad feeling about it from the beginning.

  5. You seem to be sure it leaked from a lab.

    In which case, was it a deliberate leak, or a leak due to negligence?

    Evil monsters are obviously doing what they should not be doing.

    Could you not provide a super easy guide that all including LSWMs could easily understand?

    • Rintrah’s already written articles discussing the various different potential possibilities. See:

      – In defence of the WEF-phobic conspiracy theorists: The case against bureaucratic incompetence

      – Plan B: A national address to the population

      And for articles specifically discussing the origins of the virus:

      – Yes, of course it came from a lab

      – They left the stitches in: The lab origins of SARS-COV-2

      • It came from a lab, but nothing leaked. The Wuhan Chinese, all that they had was the blank version of the universal epitope carrier spike protein backbone – from UNC and Baric with that simp EcoHealth guy acting as the bagman. The real virus was dumped in China just like everywhere else.

        The Coof is also engineered to act as a bacteriophage and this is how the original 2019 dispersal was done (via ready to eat foods). Every retard was wearing masks, when those same retards were in fact catching it in their food. The virus then kicks the game off via dis-regulating the gut-lung axis, then hitting up the lungs from the inside out with macrophages eating up all the syncytia and then the pulmonary edema.

        • It was a deliberate leak, not accidental?

          If only Rad would present the whole episode in a simple way without going into the technical details.

  6. Does the serotype development raise the prospect that everyone will initially be sicker when they catch a strain from a serotype they haven’t had before? Like with dengue? And it’s just how well you eventually fight it off that differs?

    • >Does the serotype development raise the prospect that everyone will initially be sicker when they catch a strain from a serotype they haven’t had before? Like with dengue?

      Once you have different serotypes, there’s a fair chance they evolve to abuse the antibody response induced by the other serotypes, as happened with Dengue.

      This is why you don’t want to vaccinate young people against a virus like this with inactivated vaccines.

  7. This analysis and the implied end state (as well as by GVB, I believe) assume just two groups, vaccinated and unvaccinated. Essentially, all vaccinated will die early, etc.

    But isn’t vaccination / vaccination response a continuum? Some had two shots, some 8. Some got hot lots, some got essentially saline, some were infected prior and may have a more natural response. Does this mitigate the most dire scenarios? Or is the evidence pointing to and all or nothing status re. vaccines?

    • Of course. There are endless nuances to it all.

      I care about explaining, based on actual evidence from the literature, what the problem is.

      People have this realization, at a deep guttural level, that this vaccine was a terrible idea. It’s like the sort of instinctive terror you feel when you visit a house where a horrible murder happened.

      But they’re not able to comprehend rationally what the problem is.

      That’s what I try to explain: It’s a violation of the laws of nature.

      • I am a pureblood, no throat or nose swabs either, working in a company in a blue part of the US with probably 95% co-workers being jabbed. Nobody suspects I am not jabbed.

        I am the only one who has not been sick since I joined seven months ago.

        Nobody, I mean nobody is talking about the jabs any longer. Any mention of covid gets quickly ignored and buried. They want to forget about the whole thing. If a tree falls in the forest and nobody hears it, did it really fall?

        • I haven’t had the shots, but I do test weekly since I am required to for my volunteer position since I am not jabbed. I haven’t been sick since the pandemic started, but that is not surprising since I try hard not to get sick since I have a very old person at home. I have been reading about how many coughing people there are, but only now, after a cross country flight yesterday, did I hear the coughs. The guy who drove me to the airport asked me if I had allergies too as he sniffled. The person ten seats ahead of me on the flight. And especially depressing, the very young lady who was next to me; she intermittently had a very deep cough, poor kid.

          There is right now a big, big sewage spike in the SF Bay Area, in one of the non-county wastewater monitoring systems; a university system. I assume the county systems will follow suit.

          I am not sure that vaccinated people want to forget. I think they largely have forgotten. I don’t think they can think about covid and shots even if they try.

          • “There is right now a big, big sewage spike in the SF Bay Area, in one of the non-county wastewater monitoring systems; a university system.”

            That’s interesting. In The Netherlands, levels of SARS2 in sewage are extremely low right now:

            https://www.rivm.nl/corona/actueel/weekcijfers

            It looks to be “The Vanishing Act Part 2” which is very worrying. A quote from Radagast:

            “And it seems to me we’re moving towards the worst of all possible scenarios as a result: The Vanishing Act.

            The vanishing act is what happens when the virus recedes and thereby allows the wall of antibodies to recede as well. It would become hard to monitor the ongoing evolution of the virus.

            And then eventually, you notice the rise of a cocktail of highly immune evasive variants, that can silently spread in our bodies for a long time without recalling the antibody response. They would be intrinsically highly virulent and that would be further enhanced in practice by the waning of the antibodies.”

            (Evolution towards increased interferon suppression, June 2023)

          • The high concentration one is Stanford’s CODIGA. Look at data.wastewaterscan.org (may be hard to view on a small phone screen). Select SARS-CoV-2 on the left menu. With no specific reason why Stanford should lead in time, it’s just an outlier, possible measurement error.

          • Stanford always has its results up about a week before anyone else in the region. So it wouldn’t be leading in time; it would just be results tested and posted earlier. The last time this happened it was a real signal. I would not expect a measurement error, but we can hope.

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The patients in the mental ward have had their daily dose of xanax and calmed down it seems, so most of your comments should be automatically posted again. Try not to annoy me with your low IQ low status white male theories about the Nazi gas chambers being fake or CO2 being harmless plant food and we can all get along. Have fun!

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