"The prevailing situation is that most of the authors warning about a Marek’s disaster for SARS-CoV-2, and reading the tea-leaves of government statistics to divine whether it has already arrived, do not seem deeply curious about actual virology or the immune system"
As someone who actually writes and fixes software I do not have the liberty to say "this bug is clearly another example of Original Antigenic Sin or a case of Antibody Dependent Enhancement!"
I actually have to understand what is going wrong and fix it and there does seem to be a lot of handwaving out there without reference to actual mechanisms.
"However, they also showed that the vaccine altered the production of inflammatory cytokines by innate immune cells following stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli.
Following vaccination, innate immune cells had a reduced response to toll-like receptor 4 (TLR4), TLR7 and TLR8 – all ligands that play an important role in the immune response to viral infection.
Neta and colleagues also found that cytokine responses to fungi were increased following vaccination."
* the current narrow spectrum vaccines will induce rapid evolution triggering a rapid never ending series of related pandemics
* rapid escape evolution increases the probability of worse variants and extinguishes variants that may be more mild and currently somewhat protective.
* in normal evolution no preference is made between large and small mutations but with vaccines, the mutations that confer survival become much more important and require complete escape.
* As a matter of fact, vaccines never allow the small changes that might promote co-existence with virus, because the vaccines remove these variants from the milieu.
Which seems weird to me, as surely if you only need to circumvent spike-based antibodies, the changes are only to the spike, and thus small changes?
I must be missing something more than a degree in microbiology / virology.
You wrote about Forever Spike about 3 weeks ago. Does this current article contradict that—has your thinking evolved?
I think there's no question that humanity has shown amazing hubris in regards to its attempted manipulations, of the immune system which is so incredibly complex. I struggle to stay above water with a lot of this stuff, despite having spent the last 12 years reading everything I can about the immune system after having been diagnosed with a mystery neuropathy that is thought to be autoimmune.
The idea of Immune Equilibrium is fascinating and I'll read about that next. I'm already open to the concept through familiarity with intentional self-infection with helminths (parasitic worms) in order to stimulate the immune system.
At age 67, I'm very glad that I had all the measles and chickenpox as a kid. The worst result for me of chickenpox was that I missed a trip to Disneyland. Now I wonder if my immune system might be compromised because I never managed to get the mumps (only half kidding.)
Thanks for this perspective. I have always found the Marek's outcome unlikely, and I have made some similar arguments albeit not from an immune equilibrium perspective.
In addition to the points that you make, a Marek's situation is an outlier: we have been vaccinating humans and animals with leaky vaccines against all manner of diseases for decades and Marek's is the only one that has become lethal in response. In a sense this is analogous to the outlier position of smallpox - a virus that was uniquely eradicable and is being used to suggest that SARS-CoV2 or other viruses will follow a similar trajectory to eradication if only we vaccinate hard enough.
Fear is rampant, and both sides want something to be afraid of. It's not difficult to see what this looks like from the mainstream perspective, but in the alternative camp it is taking the form of giving far more credence to the scariest conceivable outcome (a virus that kills unvaccinated people, vaccine treadmill forever, oh my!) than is justified by the facts on the ground.
Was this essay in response to el gato malo's latest?
Also: is the basic premise of your essay that the vaccine really targets only the spike, so that's pretty much all that's evolving, which means there's not really any pressure on making it more virulent. And because natural immunity hits as many viral proteins as it can it will continue to develop a robust, ongoing response to any evolved variants?
As someone commented below I will need to re-read this a couple of times. This is my first attempt at confirming understanding.
Let us think of the multicellular organism as a hotel.
I started writing an essay and went with "world". I prefer your optimism to the marek doomsayers, and wonder how hard nocebo would work in this environment so deeply steeped in fear and propaganda.
Excellent, well-written and helps my understanding of how viruses propagate and evolve. I find this more accessible than the previous articles. Thanks!
I also have not been concerned about the unvaccinated-for-covid in terms of Marek's-like evolution and losing immunity, both because of the broad antibody memory to prior encounters, and because of treatments which will continue to work. Even unvaccinated chickens are claimed to survive Marek's when treated so as to slow down the viral replication (e.g. with lysine).
For the covid-vaccinated, though, it seems like ADE and OAS are real possibilities, or am I missing something?
I liked this statement a great deal:
"The prevailing situation is that most of the authors warning about a Marek’s disaster for SARS-CoV-2, and reading the tea-leaves of government statistics to divine whether it has already arrived, do not seem deeply curious about actual virology or the immune system"
As someone who actually writes and fixes software I do not have the liberty to say "this bug is clearly another example of Original Antigenic Sin or a case of Antibody Dependent Enhancement!"
I actually have to understand what is going wrong and fix it and there does seem to be a lot of handwaving out there without reference to actual mechanisms.
Not sure where I got this link, but it's very well written, very readable and pretty sure supports what you've written here:
https://www.juliusruechel.com/2021/09/the-snake-oil-salesmen-and-covid-zero.html
Let me know if this is inappropriate to comment but I found this interesting also:
https://www.news-medical.net/news/20210510/Research-suggests-Pfizer-BioNTech-COVID-19-vaccine-reprograms-innate-immune-responses.aspx
Pre-print study:
"However, they also showed that the vaccine altered the production of inflammatory cytokines by innate immune cells following stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli.
Following vaccination, innate immune cells had a reduced response to toll-like receptor 4 (TLR4), TLR7 and TLR8 – all ligands that play an important role in the immune response to viral infection.
Neta and colleagues also found that cytokine responses to fungi were increased following vaccination."
Sounds like a confused immune system to me?
Interesting twitter thread here: https://twitter.com/letsthinkdeeply/status/1447755555938967561
His argument (unsupported IMO):
* the current narrow spectrum vaccines will induce rapid evolution triggering a rapid never ending series of related pandemics
* rapid escape evolution increases the probability of worse variants and extinguishes variants that may be more mild and currently somewhat protective.
* in normal evolution no preference is made between large and small mutations but with vaccines, the mutations that confer survival become much more important and require complete escape.
* As a matter of fact, vaccines never allow the small changes that might promote co-existence with virus, because the vaccines remove these variants from the milieu.
Which seems weird to me, as surely if you only need to circumvent spike-based antibodies, the changes are only to the spike, and thus small changes?
I must be missing something more than a degree in microbiology / virology.
You wrote about Forever Spike about 3 weeks ago. Does this current article contradict that—has your thinking evolved?
I think there's no question that humanity has shown amazing hubris in regards to its attempted manipulations, of the immune system which is so incredibly complex. I struggle to stay above water with a lot of this stuff, despite having spent the last 12 years reading everything I can about the immune system after having been diagnosed with a mystery neuropathy that is thought to be autoimmune.
The idea of Immune Equilibrium is fascinating and I'll read about that next. I'm already open to the concept through familiarity with intentional self-infection with helminths (parasitic worms) in order to stimulate the immune system.
At age 67, I'm very glad that I had all the measles and chickenpox as a kid. The worst result for me of chickenpox was that I missed a trip to Disneyland. Now I wonder if my immune system might be compromised because I never managed to get the mumps (only half kidding.)
OK, bottom line for the rest of us; is it worthwhile to get vaxxed?
An interesting example of the sorts of things you're discussing here - looks like (?) RSV hides + gets reactivated by COVID or vaccine - Japan major RSV outbreak: https://twitter.com/GreatBillDixon/status/1446626420839616516
Thanks for this perspective. I have always found the Marek's outcome unlikely, and I have made some similar arguments albeit not from an immune equilibrium perspective.
In addition to the points that you make, a Marek's situation is an outlier: we have been vaccinating humans and animals with leaky vaccines against all manner of diseases for decades and Marek's is the only one that has become lethal in response. In a sense this is analogous to the outlier position of smallpox - a virus that was uniquely eradicable and is being used to suggest that SARS-CoV2 or other viruses will follow a similar trajectory to eradication if only we vaccinate hard enough.
Fear is rampant, and both sides want something to be afraid of. It's not difficult to see what this looks like from the mainstream perspective, but in the alternative camp it is taking the form of giving far more credence to the scariest conceivable outcome (a virus that kills unvaccinated people, vaccine treadmill forever, oh my!) than is justified by the facts on the ground.
Was this essay in response to el gato malo's latest?
Also: is the basic premise of your essay that the vaccine really targets only the spike, so that's pretty much all that's evolving, which means there's not really any pressure on making it more virulent. And because natural immunity hits as many viral proteins as it can it will continue to develop a robust, ongoing response to any evolved variants?
As someone commented below I will need to re-read this a couple of times. This is my first attempt at confirming understanding.
Let us think of the multicellular organism as a hotel.
I started writing an essay and went with "world". I prefer your optimism to the marek doomsayers, and wonder how hard nocebo would work in this environment so deeply steeped in fear and propaganda.
Excellent, well-written and helps my understanding of how viruses propagate and evolve. I find this more accessible than the previous articles. Thanks!
I also have not been concerned about the unvaccinated-for-covid in terms of Marek's-like evolution and losing immunity, both because of the broad antibody memory to prior encounters, and because of treatments which will continue to work. Even unvaccinated chickens are claimed to survive Marek's when treated so as to slow down the viral replication (e.g. with lysine).
For the covid-vaccinated, though, it seems like ADE and OAS are real possibilities, or am I missing something?
Nice write up. I am going to have to re-read this at least 2 or 3 times!