Open (More or Less) Post on Covid 5

[ecosophia]

The semi-open posts  I've hosted here on the Covid-19 narrative, the inadequately tested experimental drugs for it, and the whole cascading mess surrounding them have continued to field a huge number of comments, so I'm opening another space for discussion. The rules are the same as before: 

1. If you plan on parroting the party line of the medical industry and its paid shills, please go away. This is a place for people to talk openly, honestly, and freely about their concerns that the party line in question is dangerously flawed and that actions being pushed by the medical industry et al. are causing injury and death. It is not a place for you to dismiss those concerns. Anyone who wants to hear the official story and the arguments in favor of it can find those on hundreds of thousands of websites.

2. If you plan on insisting that the current situation is the result of a deliberate plot by some villainous group of people or other, please go away. There are tens of thousands of websites currently rehashing various conspiracy theories about the Covid-19 outbreak and the vaccines. This is not one of them. What we're exploring is the likelihood that what's going on is the product of the same arrogance, incompetence, and corruption that the medical industry and its tame politicians have displayed so abundantly in recent decades. That possibility deserves a space of its own for discussion, and that's what we're doing here. 

3. If you don't believe in treating people with common courtesy, please go away. I have, and enforce, a strict courtesy policy on my blogs and online forums, and this is no exception. The sort of schoolyard bullying that takes place on so many other internet forums will get you deleted and banned here. No, I don't care if you disagree with that: my journal, my rules. 

With that said, the floor is open for discussion. 

Comments

Immune tolerance hypothesis

[(Anonymous)]

Something strange is clearly going on with regard to the vaccines, aside from the high risk of adverse effects. Despite evidence that they provide protection against symptomatic infection and severe illness, many countries with the highest vaccination rates have the highest illness and hospitalization rates, and the current wave of infection is both much stronger than would be expected in the northern hemisphere summer and also failing to drop off rapidly after a peak as occurred with past waves and the first Delta wave in India. In Israel, where a booster campaign is well underway, positive cases continued to rise even as hospitalizations leveled off, and the case rate is now among the highest of any country on Earth.


Over the past few days I have developed a hypothesis that could help to explain:

--High disease prevalence in regions with high uptake of genetic vaccines.

--Increasing disease prevalence following widespread booster vaccination in Israel.

--High ratios of unvaccinated to vaccinated hospital patients.

--Much better vaccine protection against severe illness than against infection.

--Maintained vaccine protection against severe illness over time despite waning immunity.

--Inferior vaccine protection against infection compared to natural immunity, despite comparable levels of neutralizing antibodies and T/B-cell activation.

--Higher rates of asymptomatic infection among vaccinated people despite limited testing.

--Political refusal to test asymptomatic vaccinated people for infection under most circumstances.


The hypothesis is that genetic vaccines are inducing partial immune tolerance to spike protein, likely through a regulatory T-cell response. If any commenters know immunologists or vaccinologists, I would be very interested to hear their thoughts with regard to this idea.


Tolerance is the collective term for a variety of mechanisms used by the human immune system to prevent autoimmunity. Primary tolerance occurs during immune cell development in the bone marrow, and acts to weed out developing immune cells that generate autoreactive antibodies or other autoimmune responses. Secondary tolerance, which is the main focus here, acts to mitigate the effects of autoreactive responses that are already in existence. One of the mechanisms of secondary tolerance is the development of regulatory T-cells, which act to tone down immune responses to particular antigens.


Viruses can exploit tolerance in order to evade the immune system, and this notably occurs with HIV. The viral envelope protein is sufficiently similar in form to a human protein (histone H2A) that an effective antibody response is blocked by tolerance mechanisms, and people with certain autoimmune conditions compromising these tolerance mechanisms actually mount a more effective antibody response against HIV. (https://www.sciencedirect.com/science/article/abs/pii/S0952791516301522)


Increasing tolerance to a pathogen can paradoxically decrease severe disease, when severe disease involves an immune overreaction/cytokine storm rather than actual viral tissue damage. Such is the case with most cases of severe Covid-19 that lead to hospitalization and death. (https://pubmed.ncbi.nlm.nih.gov/33391477/) However, this protective effect comes with trade-offs. When coronavirus-family infections were studied in mice, regulatory T-cells prevented severe immunogenic illness but increased the risk of viral persistence and chronic infection. Furthermore, regulatory T-cell activation can non-specifically dampen immune response to other pathogens, leading to increased incidence of secondary infections. (https://www.mdpi.com/1999-4915/4/5/833/htm)


The main biochemical difference between genetic vaccines and conventional vaccines is that the former present protein antigens to the immune system on the surface of human cells, while the latter present antigens on inactivated viruses or other inert injected particles. Furthermore, when genetic vaccines “infect” a large number of muscle cells, or vessel wall cells, or heart cells, causing them to produce spike protein, the immune system creates conflicting signals. The generated antibodies say “kill that foreign object!” while the self-recognition systems say “that thing just showed up on a bunch of our cells, must be OK!” For this reason, we might expect genetic vaccines to be more likely to induce anti-autoimmunity tolerance mechanisms.


Interestingly, there is an mRNA vaccine in development that is specifically designed to induce tolerance as a treatment for autoimmune disease through activation of regulatory T-cells. The Nature paper describing that work curiously includes the following paragraph: “Sahin and colleagues have clearly demonstrated the potential of RNA lipoplex vaccines to deliver a non-inflammatory form of an mRNA vaccine encoding a self antigen to prevent and limit autoimmune disease in mice. It is noteworthy that m1Ψ-containing mRNA is also used for the COVID-19 mRNA vaccine, indicating that the pro- versus anti-inflammatory nature of m1Ψ mRNA vaccines can be modulated depending on the specific antigen and specific encapsulating lipid formulation. In the case of the BNT162b2 vaccine for COVID-19, the antigen is a foreign protein formulated in an immunostimulatory lipid nanoparticle. In the present study, the antigen is a self protein delivered in a non-immunogenic lipoplex formulation, and an extra mRNA purification step removes any residual immunostimulatory molecules. This method allows antigen presentation in the absence of inflammation and co-stimulation, preferential expansion of pre-existing T(reg) cells, and possibly also their de novo development.” (https://www.nature.com/articles/s41587-021-00880-0)



In other words, they claim that the immune response to an mRNA vaccine can be switched between tolerance and immunity by choosing a self or foreign protein and selecting a pro- or anti-inflammatory lipid formulation for the encapsulation. I highly doubt that it’s that simple, and I strongly suspect that unintentional induction of partial tolerance is a likely side effect of any genetic vaccine.



Conveniently, in the case of Covid-19, it turns out that tolerance is protective against severe disease, and indeed some treatment efforts have focused specifically on enhancing immune tolerance (https://journals.ekb.eg/article_92759.html). However, immune tolerance may also be associated with prolonged virus shedding (https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30273-X/fulltext). If the genetic vaccines do indeed induce partial immune tolerance, that could help to explain their impressive efficacy against the sort of immune overreaction that leads to hospitalization and death, while also explaining their comparative weakness in preventing infection and transmission of the virus. If “long covid” is, as many scientists suspect, partially induced by autoreactive antibodies, then it would also make sense that genetic vaccines could reduce or eliminate those symptoms by inducing tolerance. This could help to explain the phenomenon that vaccination sometimes alleviates long covid, and also reduces the incidence of long covid in breakthrough infections.


This is an eminently testable hypothesis that can be explored by examining regulatory T-cell responses (or other immune tolerance responses) following vaccination. To date, I can find no evidence that anyone has done this, but I would hope that it will happen in the near future, and the results will be illuminating.


Tolerance is not an on/off phenomenon but rather a wide spectrum ranging from the complete immune acceptance of most of our own proteins to the extreme reactogenicity of a serious peanut or bee sting allergy. Tolerance mechanisms can coexist with immunity mechanisms, such that tolerance begins to become apparent as the level of neutralizing antibodies declines. And to be clear, I am not hypothesizing that the genetic Covid-19 vaccines function by virtue of inducing tolerance. It has been well-demonstrated that they induce a strong neutralizing antibody response. I am instead suggesting that they may *also* be inducing partial tolerance, and that this effect may help to explain strong protection against severe (immune overreaction) disease, high rates of illness transmission in high-vax areas, and possibly also significant declines in immunity after 4-6 months despite continuing high antibody levels.


If indeed the genetic Covid-19 vaccines are inducing partial tolerance, we can make certain predictions:



1. Genetic vaccines will be extremely effective at preventing severe disease, but much less effective in terms of preventing infection. (True)

2. As vaccine immunity wanes, protection against cytokine-storm-type severe disease will be maintained. (Seems to be true)

3. As vaccine immunity wanes, vaccinated people will increasingly carry and spread the virus, and population-level viral prevalence will rise in areas with a high uptake of genetic vaccines. (True) Vaccinated people will be more likely to be asymptomatic carriers. (True, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext)

4. This will lead to a significant wave of illness transmission which will disproportionately affect unvaccinated people (who are not protected against severe disease). (True right now across the US and much of the world)

5. Booster shots will further increase tolerance, leading to an increased level of disease prevalence across the population. (True in Israel)

6. As immunity wanes and new antibody-resistant variants emerge, vaccinated people will be more vulnerable to long-term/chronic infection with high viral loads. Due to the protective effects of tolerance this will likely manifest not as typical severe Covid-19 illness (pneumonia, ventilators, cytokine storms, multiorgan failure) but rather as spike protein toxicity. So we should watch for an increase in clotting, strokes, heart attacks, myocarditis, neurological problems, etc. Vaccinated patients dying of these conditions may not be tested for Covid-19 and so likely will not be counted as covid deaths, and the myth of vaccine efficacy may persist based on the original definition of “preventing severe Covid-19 disease” even as we experience a wave of mysterious illness and death. Furthermore, vaccinated people may be more vulnerable to other infections due to regulatory-T-cell mediated general immune suppression. Should ADE develop, with non-neutralizing antibodies facilitating enhanced infection or direct infection of immune cells, tolerance could well lead to further exacerbation. However tolerance could also provide protection against cytokine storm-type reactions and accelerate the evolution of SARS-CoV2 into an endemic human pathogen, so the long-term effect of tolerance is uncertain.

7. Contrary to the shrill claims of the fearful, vaccinated people will present a much greater danger than unvaccinated people in terms of asymptomatic transmission and evolution of new variants.

8. There are likely to be significant differences between the vaccines. In particular, the two-shot series would be expected to induce greater tolerance, and possibly also greater tolerance will be evident in countries with a shorter interval between the two shots. Countries that utilized inactivated-virus vaccines are probably less likely to see tolerance effects, although they may still encounter ADE or other problems down the road.


This hypothesis presents a scenario of vaccine failure that first appears as success (because tolerance prevents severe disease), that explains the trends currently observed (unexpectedly high illness rates in high-vax areas), and that potentially portends a troubling future without invoking the still-hypothetical ADE. As with JMG’s original hypothesis, time will tell…

Mark L

Re: Immune tolerance hypothesis

[ahriman]

Just a note: data out of England seems to suggest the while it might help protect against severe disease, it actually is quite bad with preventing death - severe disease numbers are better for vaxxed, but seem worse wrt deaths

Re: Immune tolerance hypothesis

[(Anonymous)]

Tolerance could cause that, I would think. Less severe pneumonia caused by immune overreaction but more death associated with uncontrolled viral replication.

Mark L

Re: Immune tolerance hypothesis

[(Anonymous)]

Yeah i saw that thx to you. So they ran headlines here about 30x more likely to go to the icu if unvaxxd and I wondered why not just say die or talk about mortality. But they were being truthful so they left out the part about 2x liklier to die. Celadon

Re: Immune tolerance hypothesis

[tunesmyth]

What is this “data out of England” suggesting increased mortality in vaxed vs unvaxed? If true and from a source widely considered reputable, it needs amplification.

Re: Immune tolerance hypothesis

[ahriman]

https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201

Re: Immune tolerance hypothesis

[(Anonymous)]

The consensus is they didnt adjust on over under 50 so factor that in. Older people more likely to vax and more likely to die independently of each other in at least basic aspect. But other than that adjustment the data shows more likely to DIE all cause mortality if vaxxd, and enough different cant just be the demographic component alone. that seemed last weeks consensus from those here that crunched it. Someone can correct me if i am misremembering. -Celadon

Re: Immune tolerance hypothesis

[(Anonymous)]

Is that actually corrected for age (and not just their stupid under-50 vs over-50)? Without that, it's impossible to draw meaningful conclusions.

Re: Immune tolerance hypothesis

[escorcher]

If I get you right this means indications of any increasing problem may not be particularly clear, at least to start, as the indicators won't be more ill people with serious CoVid and could very easily be waved away as unrelated.

Re: Immune tolerance hypothesis

[(Anonymous)]

Yes. If tolerance is occurring I would expect to see increasingly more infections in vaccinated people which would be associated with clotting problems and sudden deaths, but relatively few vaccinated people hospitalized with the classic low oxygen/pneumonia that leads to extended ICU stays on ventilators.

Without adequate testing of vaccinated people to verify infection and to classify deaths accordingly, this could easily be waved away or ignored.

Mark L

Re: Immune tolerance hypothesis

[escorcher]

This is useful to visualize excess mortality (all causes) from the several year average. e.g. UK tracking upwards a little to 15% above average mid August. U.S. about 5% above average - early August.

https://ourworldindata.org/grapher/excess-mortality-p-scores?country=USA~GBR

Re: Immune tolerance hypothesis

[(Anonymous)]

The basic scenario seems feasible to me.

I must say that all sides seem to expect the near-term future to be very ugly and are laying the groundwork to blame the Others for it. Right now some vaxxed people are saying that it's all the fault of the wicked unvaxxed that the hospitals are filling up, even though vaxxed people are also spreading covid. You describe this as "the shrill claims of the fearful," but then speculate about how the vaxxed will "present much greater danger" to the innocent unvaxxed by generating new variants, though just as much evolution occurs during replication in unvaxxed people. And goodness knows, the people who claim that you can get every disease in the book from passing a vaccinated person on the sidewalk could be called shrill and fearful.

Suppose that this time next year a lot of people, vaxxed and unvaxxed equally, are dying of the Omega strain. Will the whole discourse still be about assigning blame? The vaxxed saying the unvaxxed must have made it happen, and vice versa? A lot of this speculation seems to me to be about setting up that fight - which means that nobody on either side thinks next year it will just be common cold coronavirus #5, and they're all scrambling to set up scapegoats.

Re: Immune tolerance hypothesis

[(Anonymous)]

I am discovering that in this emotionally charged time, I must be very careful in my choice of words because everyone is hyper alert for evidence of judgment or blame.

I'm not really interested in blaming anyone, just in trying to understand what is going on. Which is to say that in no way did I formulate this hypothesis as an excuse to justify blaming vaccinated people for spreading covid.

Mark L

Re: Immune tolerance hypothesis

[(Anonymous)]

Regardless of what happens I expect the narrative on almost all sides to be about assigning blame.

Re: Immune tolerance hypothesis

[(Anonymous)]

...though just as much evolution occurs during replication in unvaxxed people

That's not quite my understanding. The key point is that vaxxed tend to encourage the survival of mutants with different spike proteins. Those mutants have, after all, a better chance of evading the imperfect immune response produced by the vaccines. There is no such advantage in the unvaxxed. There is an evolutionary pressure in anything but full sterilizing immunity.

The evolutionary mechanism seems much the same to me as what drives the development of antibiotic resistance.
(Apologies to Geert Van den Bossche if I've butchered anything too badly in this layperson's summary.)

*Ochre Harebrained Curmudgeon*

Re: Immune tolerance hypothesis

[(Anonymous)]

I think it's been "common cold coronavirus #5" all along. My concerns with it relate not to the virus itself, but the reaction to it: after this scale of panic, how do we ever return to normal without major crisis? And by normal, I don't mean "2019", but rather a state of affairs where governments tolerate Covid-19 infections and treat it like the respiratory virus that it is.

Re: Immune tolerance hypothesis

[(Anonymous)]

Which is an interesting point and seems like a tacit admission that vaccines don’t work or don’t work as advertised. After all if the vaccinated are getting it and dying of it in sufficient numbers to blame the unvaxxed…

Re: Immune tolerance hypothesis

[(Anonymous)]

“Though just as much evolution occurs during replication in unvaxxed people.”

While I will certainly agree with you that plenty of mutations will take place in either group, to me it’s a bit more like the theory of Antibiotic resistant tuberculosis being bred in Russian prisons. Not necessarily maliciously, just not enough meds to run a complete course on convicts. Just for example, say you had 50% of the antibiotics needed to treat an outbreak in a prison.
The options are:
A. divide the drugs evenly, even though it won’t cure people or
B. to withhold from some prisoners so that others can have the full course. The Russian authorities chose the former. (https://sciencecases.lib.buffalo.edu/files/tb_game.pdf) selected because it has a bibliography even though it’s a case study exercise.
In this particular case someone with a “Partial treatment” winds up breeding a stronger version of the infection.
Applying that to COVID if people with a partial protection (I.e. less severe infections but “leaky” vaccines) evolve a stronger virus than the ordinary path of evolution and mutations. Specifically because the virus is adapting to at least one form of protection.

Re: Immune tolerance hypothesis

[escorcher]

Had another thought Mark, and is basically the same point to consider as I posted on last week's discussion. Couldn't the difficulty in protection of the respiratory tract by vaccine induced antibodies(and probably to a lesser extent previous infection - IgA vs IgG) together with the increase of infectiousness associated with Delta explain what we're seeing? Difficulty in protecting respiratory tract discussed here:
https://www.abc.net.au/news/health/2020-04-17/coronavirus-vaccine-ian-frazer/12146616

Re: Immune tolerance hypothesis

[(Anonymous)]

That could be part of it certainly, but it doesn't explain why there would be more infections in areas with more genetic vaccinations relative to areas with fewer vaccinations. It really appears that these vaccines are acting to increase the overall level of viral transmission in the population, which is being blamed on the infectiousness of Delta - despite the fact that the Delta variant is present worldwide but is not causing the same level of illness in many less-vaccinated places.

I am trying to insert immune tolerance into the conversation, because I think it needs to be seriously considered along with ADE, OAS, and the other potential issues, and I think we might already have evidence that it is occurring.

Mark L

Re: Immune tolerance hypothesis

[(Anonymous)]

Although I wrote that no one has specifically investigated a regulatory T cell-mediated tolerance effect from the vaccines, I did discover one paper yesterday that has investigated Pfizer vaccine-responsive immune reprogramming in general and found some concerning results pointing toward potential tolerance responses.

"The induction of tolerance towards stimulation with TLR7/8 (R848) or TLR4 (LPS) ligands by BNT162b2 vaccination may indicate a more balanced inflammatory reaction during infection with SARS-CoV-2, and one could speculate whether such effect may be thus useful to regulate the potential over-inflammation in COVID-19, one of the main causes of death (Tang et al., 2020). On the other hand, inhibition of innate immune responses may diminish anti-viral responses."

"This may hamper the initial innate immune response against the virus, as defects in TLR7 have been shown to result in and increased susceptibility to COVID-19 in young males (Van Der Made et al., 2020). These results collectively demonstrate that the effects of the BNT162b2 vaccine go beyond the adaptive immune system and can also modulate innate immune responses."

"In conclusion, our data show that the BNT162b2 vaccine induces effects on both the adaptive and the innate branch of immunity and that these effects are different for various SARS-CoV-2 strains. Intriguingly, the BNT162b2 vaccine induces reprogramming of innate immune responses as well, and this needs to be taken into account: in combination with strong adaptive immune responses, this could contribute to a more balanced inflammatory reaction during COVID-19 infection, or it may contribute to a diminished innate immune response towards the virus."

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1.full-text

Mark L

Re: Immune tolerance hypothesis

[(Anonymous)]

Mark -- Could you explain more your reasoingn behind #8?

8. There are likely to be significant differences between the vaccines. In particular, the two-shot series would be expected to induce greater tolerance, and possibly also greater tolerance will be evident in countries with a shorter interval between the two shots. Countries that utilized inactivated-virus vaccines are probably less likely to see tolerance effects, although they may still encounter ADE or other problems down the road.

Would you also say there will be different levels of tolerance between those who stopped after the first round of shots, and those who keep choosing to get boosters?

Re: Immune tolerance hypothesis

[(Anonymous)]

I can't say anything for sure, however I would expect boosters to generally enhance tolerance. The human body doesn't actually want to kill the otherwise-healthy cells that express spike protein following genetic vaccination, and so it is likely to tone down the initial immune attack to counteract the effect of antibodies. That's my reasoning anyway, backed up by a very limited amount of data so far.

As for the interval hypothesis, that's based largely on my own personal experience with developing and being successfully treated for bee sting allergy through a series of injections, and reading up on the science in the process. It turns out in that case that 2-4 weeks between exposures maximizes a tolerance response, while longer intervals are less effective and can sometimes have the opposite effect.

Mark L

Re: Immune tolerance hypothesis

[(Anonymous)]

Mark, that's a thoughtful and thought provoking hypothesis. Would it be alright if I reposted it elsewhere (linking back to your comment here)?

Re: Immune tolerance hypothesis

[(Anonymous)]

Certainly.

Mark L