8 ms·

Vaccine-Induced Covid-19 Mimicry Syndrome

101 points by clon 5y ago

fxtentacle 5y ago
Isn't it too be expected that when you train people's immune response by injecting mimicry spike proteins that people will react very similar to when they receive actual spike proteins?
- rrmm 5y ago
  I think this research is seeking to explain the disparity between the AZ vaccine reactions and others.
- shlant 5y ago
  neither mRNA (Pfizer + Moderna) nor viral vector (AZ + J&J) vaccines "inject" spike proteins. They use different delivery mechanisms (lipid nanoparticles or adenoviruses) for the genetic code that is used to create the spike proteins. The article referenced is suggesting that the rare but serious clotting issues related to the adenovirus vaccines is caused by an errant processing of the spike gene which results in production of truncated spike protein that has soluble properties which results in it being excreted into the body. This soluble spike protein can then cause blood clotting issues when binding to endothelial cells in blood vessels. So to attempt to answer your question: we expect the vaccine to result in the production of the spike protein in the body which your body then builds an immune response to which protects you from future infection. However, either due to a problem with the vaccine or how the spike protein is created in the body (I'm am not sure which - someone let me know), in rare instances a truncated spike protein can be produced that is slightly different than expected and results in blood clotting issues.
rozab 5y ago
The (open!) comments section on there is probably the most advanced I've ever seen on the internet.
- ithkuil 5y ago
  probably because they are moderated
Angostura 5y ago
Just in case there are others out there who like me stumbled on the reference to 'codon optimized' in the abstract - here's a nice explanation: https://blog.addgene.org/to-codon-optimize-or-not-that-is-the-question https://blog.addgene.org/to-codon-optimize-or-not-that-is-th...
fsiefken 5y ago
What I want to know is if the transcription of the spike protein of the SARS-CoV-2 also leads to dangerous C-terminal truncated spike proteins or that SARS-CoV-2 transcription by definition doesn't lead to truncated spike proteins. If so than catching SARS-CoV-2 is equally risky on this front. From the abstract: "..transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels"
- usrusr 5y ago
  I was asking myself the same question because some of the wording used is quite suggestive to a layman reader like me. But after some Wikipedia my answer is: no, the actual virus carries its blueprint in RNA form that doesn't go through that transcription step where the errors occur. In JVM lingo, it's as if one was .class and the other was a single-class .jar and somehow certain byte sequences were less reliable during unzip than others. And as a consequence, those byte sequence are avoided by programs routinely distributed as .jar but used quite generously by those distributed as .class. Now they took some snippets from a codebase that is deeply rooted in the ".class" tradition and inserted it into a vector from the ".jar" side and the unzip errors happened to be rare enough to not light up during QA.
isoprophlex 5y ago
What a fantastic read. The title might be a bit cryptic; the authors propose a convincing hypothesis that explains why Astrazeneca and JNJ vaccines cause rare but fatal blood clotting incidents. TLDR: mRNA vaccines turn their payload into proteins in the cytosol. Conversely, DNA vaccines (astrazeneca, JNJ) must first use the nucleus to turn their DNA into mRNA. This incurs so-called post-~translational~ (edit: post-transcriptional) modification to the genetic material prior to protein synthesis. As it turns out, some of these unforseen modifications create soluble spike protein fragments that bind to epithelial cells. This in turn causes inflammatory, and coagulant, activity, which leads to the lethal side effects that are sometimes observed.
- linuxftw 5y ago
  This is why you don't skip the animal trials.
  - arrrg 5y ago
    Why do you say that? As far as I know the vector vaccines were tested on animals. Nothing was skipped. The issue is more that this side effect is so rare that it didn’t register even during the quite large phase 3 trials. This is to be expected. If side effects are rare enough you just won’t find them during trials. That’s why it’s important to monitor the vaccine rollout for all vaccines.
    - linuxftw 5y ago
      We don't know the side effects are rare because the reporting mechanism for side effects is nearly non existent. If you want to use the VAERS data, the side effects, include death, are not really that rare, in fact, these are the most dangerous vaccines ever produced based on that data. If that data isn't good enough, you'll have to provide data that is.
      - hedora 5y ago
        Link?
vlovich123 5y ago
Does this only apply to the adenovirus vaccine or could this happen with the mRNA ones too? It sounds like only the adenovirus, in which case the naming of the syndrome is… unfortunate in the middle of a stalling vaccine rollout. It will sow confusion I think.
- nerdponx 5y ago
  The article is pretty clear that this is not problem with the mRNA vaccines.
- linuxftw 5y ago
  It can happen in the mRNA ones too, but this misfolding will happen in the lab rather than in your cells. What percentage of an mRNA shot that is being mass produced is random biological material? We don't know, there's no kind of independent laboratory testing these things.
- hedora 5y ago
  No; the paper says the problem occurs in the cell nucleus, and the mRNA vaccines don’t enter the nucleus: https://www.pfizer.com/news/hot-topics/the_facts_about_pfizer_and_biontech_s_covid_19_vaccine https://www.pfizer.com/news/hot-topics/the_facts_about_pfize...
giantg2 5y ago
You know, my father in law had some kind of stroke about 2 weeks after his first shot. I thought maybe it was more than coincidence since there were reports of increased occurence of stroke with the virus. Hard to say if it's just coincidence or not, but this paper is making me wonder if it may have been an adverse event. The really frustrating part is that most doctors don't report things like this to VAERS. How can we have good data to analyze and find correlations if most doctors do only the legal minimum reporting?! They are only requires to report the types of known adverse events listed in the packet insert. This doesn't help identify new types of adverse events. This is the second time in as many years that I've witnessed something that has the potential to be a rare but serious issue related to vaccines not be entered by the doctors. I had to report one myself, and it looks like this other one will simply go unreported.
- axiak 5y ago
  this paper is discussing mechanisms limited to the J&J and Astrazeneca vaccines
  - giantg2 5y ago
    Are the mechanisms limited to those, or did they only investigate the proteins specific to those vaccines? My understanding is that they only looked at the spike proteins for those vaccines and did not evaluate the others. My understanding is that the proteins in the others have the potential to interact similarly with the ACE2 mechanism but were not evaluated.
    - ericbarrett 5y ago
      The issue seems to be with the DNA -> mRNA transcription required by the adenovirus vector of the J&J and AstraZeneca vaccines, leading to mutated spike proteins which can cause clots. The Pfizer/Moderna shots don't use this mechanism so weren't the subject of the paper. (This is not my specialty at all, just summarizing the abstract & what other commenters wrote since nobody replied to you yet) I'm sorry about your father-in-law.
Santosh83 5y ago
Has anybody similarly investigated the reports of cardiac inflammation following the administration of the mRNA vaccines, particularly the Pfizer one? What explains that?
- jb1991 5y ago
  > Finally, EMA has received reports of Comirnaty recipients developing myocarditis and pericarditis. “There is no indication at the moment that these cases are due to the vaccine,” wrote PRAC. https://www.raps.org/news-and-articles/news-articles/2021/5/prac-investigates-heart-inflammation-reports-with https://www.raps.org/news-and-articles/news-articles/2021/5/...
- xattt 5y ago
  This could also be a cause: https://www.theguardian.com/media/2021/may/25/influencers-say-russia-linked-pr-agency-asked-them-to-disparage-pfizer-vaccine https://www.theguardian.com/media/2021/may/25/influencers-sa...
Santosh83 5y ago
Also would a similar phenomenon be possible in an inactivated SARS-CoV2 virus vaccine?
novaRom 5y ago
TL;DR: They have found first computationally then experimentally, a high number of potential splice sites in genetic code of AstraZeneca and J&J adeno viruses. This means instead of producing Spike protein, its shorter versions may be produced by cells infected with these adenoviruses. Those short proteins can cause rare sever side effects. Quote: Here, we present first molecular evidence that vector-based vaccines encoding the Spike protein exhibit a problem that is completely absent in mRNA-based vaccines. This is due to the fact that during the vaccination step, the adenoviral DNA enters the nucleus and use the host machinery to transcribe its (trans)genes inside the nucleus. However, RNA viruses have evolved in the absence of any post-transcriptional modification systems that are usually enabled to process the primary RNA transcripts of nuclear encoded genes. In this study, we experimentally validated our assumption that potential splice events cause the production of Spike protein variants that have lost the important membrane anchor, resulting in secreted, soluble Spike protein variants.
- gmac 5y ago
  I am way outside my domain here, but the key thing I didn't quite get is why, since 20%+ of the mRNA in the mRNA vaccines is truncated sequences (https://www.bmj.com/content/372/bmj.n627 https://www.bmj.com/content/372/bmj.n627), some of those sequences don't similarly get translated into soluble proteins with similar bad effects. But I guess it has something to do with particular splice sites causing particular irregular proteins that cause the issue — and since the mechanism of mRNA truncation in the mRNA vaccines is not splicing, I guess there may be a much wider array of random truncated sequences, most of which are harmless?
jamiemchale 5y ago
Can anyone explain how long they expect this potential effect to last? The vaccine DNA presumably breaks down / dissipates after a period of time? And the spike protein fragments too? What might that period of time be?
- daanlo 5y ago
  This very rare side effect, typically happens in the first 2-3 weeks after the vaccination. Src (in German): https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Downloads-COVID-19-Vektorimpfstoff/Aufklaerungsbogen-de.pdf?__blob=publicationFile https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Down... Symptoms of the thrombosis include: extreme headaches and/or bruises (without actually hurting yourself). Src: my (potentially inaccurate) recollection of my doctor telling me about this.
  - wincy 5y ago
    I had the worst headache of my life a few days after getting the J&J vaccine, and went to the emergency room because my wife was worried I’d had Ana aneurysm or something. The ER visit happened the day before the news broke about blood clots and whatnot. The doctor told me it was absolutely unrelated to the vaccine. They did a scan with some contrast dye, said everything looked fine, and discharged me. I couldn’t do strenuous activity for over a week because I’d feel the headache again, almost like a part of the inside of my skull had been scraped, I don’t know how else to describe it.
mapgrep 5y ago
After my J&J shot, for weeks, my legs and feet would frequently feel “asleep.” Especially on waking but often during the day as well. The effect seems to have diminished (and I think mostly resolved) ~6 weeks later. No idea if it’s related to this. (This is on top of the usual reaction of chills/fatigue the first night or two. I will say the fatigue seemed to go on for a while at some modestly higher than usual baseline but I can’t really quantify it or prove it. )
deleted 5y ago
[deleted]
doggodaddo78 5y ago
I had reservations about J&J and AZ because of their complicated nature. I had more confidence in mRNA vaccines (Pfizer and Moderna) as simpler and more elegant to produce the desired immune response. Anytime there are extra steps, there's added risks something can go wrong and cause unknown or horrible side-effects.
stefantalpalaru 5y ago
> an older immune system displays more immune senescence which means that young people exhibit stronger immune reactions than elderly people, and women even stronger than men Non sequitur. Why would women have stronger immune systems than men? Also, if this theoretical mechanism is valid, why is the incidence of thromboembolism the same as before the vaccination campaign? See https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00762-5/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... > all mRNA-based vaccines should represent safe products, because the delivered mRNA will only be translated into surface antigen, without having any possibility to participate in nuclear splice events Not so fast. There's that little detail of lipid nanoparticles being highly inflammatory: https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1.full https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1....
IYasha 5y ago
What a great example of ridiculousness of web 3.0 researchsquare.com loads and then "An unexpected error has occurred." fullscreen. Disabling JS and CSS makes it worse. So un-scientific.

101 points by clon 5y ago

Isn't it too be expected that when you train people's immune response by injecting mimicry spike proteins that people will react very similar to when they receive actual spike proteins?

rrmm 5y ago
I think this research is seeking to explain the disparity between the AZ vaccine reactions and others.
shlant 5y ago
neither mRNA (Pfizer + Moderna) nor viral vector (AZ + J&J) vaccines "inject" spike proteins. They use different delivery mechanisms (lipid nanoparticles or adenoviruses) for the genetic code that is used to create the spike proteins. The article referenced is suggesting that the rare but serious clotting issues related to the adenovirus vaccines is caused by an errant processing of the spike gene which results in production of truncated spike protein that has soluble properties which results in it being excreted into the body. This soluble spike protein can then cause blood clotting issues when binding to endothelial cells in blood vessels. So to attempt to answer your question: we expect the vaccine to result in the production of the spike protein in the body which your body then builds an immune response to which protects you from future infection. However, either due to a problem with the vaccine or how the spike protein is created in the body (I'm am not sure which - someone let me know), in rare instances a truncated spike protein can be produced that is slightly different than expected and results in blood clotting issues.

rozab 5y ago

The (open!) comments section on there is probably the most advanced I've ever seen on the internet.

ithkuil 5y ago
probably because they are moderated

Angostura 5y ago

Just in case there are others out there who like me stumbled on the reference to 'codon optimized' in the abstract - here's a nice explanation: https://blog.addgene.org/to-codon-optimize-or-not-that-is-the-question https://blog.addgene.org/to-codon-optimize-or-not-that-is-th...

fsiefken 5y ago

What I want to know is if the transcription of the spike protein of the SARS-CoV-2 also leads to dangerous C-terminal truncated spike proteins or that SARS-CoV-2 transcription by definition doesn't lead to truncated spike proteins. If so than catching SARS-CoV-2 is equally risky on this front. From the abstract: "..transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels"

usrusr 5y ago
I was asking myself the same question because some of the wording used is quite suggestive to a layman reader like me. But after some Wikipedia my answer is: no, the actual virus carries its blueprint in RNA form that doesn't go through that transcription step where the errors occur. In JVM lingo, it's as if one was .class and the other was a single-class .jar and somehow certain byte sequences were less reliable during unzip than others. And as a consequence, those byte sequence are avoided by programs routinely distributed as .jar but used quite generously by those distributed as .class. Now they took some snippets from a codebase that is deeply rooted in the ".class" tradition and inserted it into a vector from the ".jar" side and the unzip errors happened to be rare enough to not light up during QA.

isoprophlex 5y ago

What a fantastic read. The title might be a bit cryptic; the authors propose a convincing hypothesis that explains why Astrazeneca and JNJ vaccines cause rare but fatal blood clotting incidents. TLDR: mRNA vaccines turn their payload into proteins in the cytosol. Conversely, DNA vaccines (astrazeneca, JNJ) must first use the nucleus to turn their DNA into mRNA. This incurs so-called post-~translational~ (edit: post-transcriptional) modification to the genetic material prior to protein synthesis. As it turns out, some of these unforseen modifications create soluble spike protein fragments that bind to epithelial cells. This in turn causes inflammatory, and coagulant, activity, which leads to the lethal side effects that are sometimes observed.

linuxftw 5y ago
This is why you don't skip the animal trials.
- arrrg 5y ago
  Why do you say that? As far as I know the vector vaccines were tested on animals. Nothing was skipped. The issue is more that this side effect is so rare that it didn’t register even during the quite large phase 3 trials. This is to be expected. If side effects are rare enough you just won’t find them during trials. That’s why it’s important to monitor the vaccine rollout for all vaccines.
  - linuxftw 5y ago
    We don't know the side effects are rare because the reporting mechanism for side effects is nearly non existent. If you want to use the VAERS data, the side effects, include death, are not really that rare, in fact, these are the most dangerous vaccines ever produced based on that data. If that data isn't good enough, you'll have to provide data that is.
    - hedora 5y ago
      Link?

vlovich123 5y ago

Does this only apply to the adenovirus vaccine or could this happen with the mRNA ones too? It sounds like only the adenovirus, in which case the naming of the syndrome is… unfortunate in the middle of a stalling vaccine rollout. It will sow confusion I think.

nerdponx 5y ago
The article is pretty clear that this is not problem with the mRNA vaccines.
linuxftw 5y ago
It can happen in the mRNA ones too, but this misfolding will happen in the lab rather than in your cells. What percentage of an mRNA shot that is being mass produced is random biological material? We don't know, there's no kind of independent laboratory testing these things.
hedora 5y ago
No; the paper says the problem occurs in the cell nucleus, and the mRNA vaccines don’t enter the nucleus: https://www.pfizer.com/news/hot-topics/the_facts_about_pfizer_and_biontech_s_covid_19_vaccine https://www.pfizer.com/news/hot-topics/the_facts_about_pfize...

giantg2 5y ago

You know, my father in law had some kind of stroke about 2 weeks after his first shot. I thought maybe it was more than coincidence since there were reports of increased occurence of stroke with the virus. Hard to say if it's just coincidence or not, but this paper is making me wonder if it may have been an adverse event. The really frustrating part is that most doctors don't report things like this to VAERS. How can we have good data to analyze and find correlations if most doctors do only the legal minimum reporting?! They are only requires to report the types of known adverse events listed in the packet insert. This doesn't help identify new types of adverse events. This is the second time in as many years that I've witnessed something that has the potential to be a rare but serious issue related to vaccines not be entered by the doctors. I had to report one myself, and it looks like this other one will simply go unreported.

axiak 5y ago
this paper is discussing mechanisms limited to the J&J and Astrazeneca vaccines
- giantg2 5y ago
  Are the mechanisms limited to those, or did they only investigate the proteins specific to those vaccines? My understanding is that they only looked at the spike proteins for those vaccines and did not evaluate the others. My understanding is that the proteins in the others have the potential to interact similarly with the ACE2 mechanism but were not evaluated.
  - ericbarrett 5y ago
    The issue seems to be with the DNA -> mRNA transcription required by the adenovirus vector of the J&J and AstraZeneca vaccines, leading to mutated spike proteins which can cause clots. The Pfizer/Moderna shots don't use this mechanism so weren't the subject of the paper. (This is not my specialty at all, just summarizing the abstract & what other commenters wrote since nobody replied to you yet) I'm sorry about your father-in-law.

Santosh83 5y ago

Has anybody similarly investigated the reports of cardiac inflammation following the administration of the mRNA vaccines, particularly the Pfizer one? What explains that?

jb1991 5y ago
> Finally, EMA has received reports of Comirnaty recipients developing myocarditis and pericarditis. “There is no indication at the moment that these cases are due to the vaccine,” wrote PRAC. https://www.raps.org/news-and-articles/news-articles/2021/5/prac-investigates-heart-inflammation-reports-with https://www.raps.org/news-and-articles/news-articles/2021/5/...
xattt 5y ago
This could also be a cause: https://www.theguardian.com/media/2021/may/25/influencers-say-russia-linked-pr-agency-asked-them-to-disparage-pfizer-vaccine https://www.theguardian.com/media/2021/may/25/influencers-sa...

Santosh83 5y ago

Also would a similar phenomenon be possible in an inactivated SARS-CoV2 virus vaccine?

novaRom 5y ago

TL;DR: They have found first computationally then experimentally, a high number of potential splice sites in genetic code of AstraZeneca and J&J adeno viruses. This means instead of producing Spike protein, its shorter versions may be produced by cells infected with these adenoviruses. Those short proteins can cause rare sever side effects. Quote: Here, we present first molecular evidence that vector-based vaccines encoding the Spike protein exhibit a problem that is completely absent in mRNA-based vaccines. This is due to the fact that during the vaccination step, the adenoviral DNA enters the nucleus and use the host machinery to transcribe its (trans)genes inside the nucleus. However, RNA viruses have evolved in the absence of any post-transcriptional modification systems that are usually enabled to process the primary RNA transcripts of nuclear encoded genes. In this study, we experimentally validated our assumption that potential splice events cause the production of Spike protein variants that have lost the important membrane anchor, resulting in secreted, soluble Spike protein variants.

gmac 5y ago
I am way outside my domain here, but the key thing I didn't quite get is why, since 20%+ of the mRNA in the mRNA vaccines is truncated sequences (https://www.bmj.com/content/372/bmj.n627 https://www.bmj.com/content/372/bmj.n627), some of those sequences don't similarly get translated into soluble proteins with similar bad effects. But I guess it has something to do with particular splice sites causing particular irregular proteins that cause the issue — and since the mechanism of mRNA truncation in the mRNA vaccines is not splicing, I guess there may be a much wider array of random truncated sequences, most of which are harmless?

jamiemchale 5y ago

Can anyone explain how long they expect this potential effect to last? The vaccine DNA presumably breaks down / dissipates after a period of time? And the spike protein fragments too? What might that period of time be?

daanlo 5y ago
This very rare side effect, typically happens in the first 2-3 weeks after the vaccination. Src (in German): https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Downloads-COVID-19-Vektorimpfstoff/Aufklaerungsbogen-de.pdf?__blob=publicationFile https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Down... Symptoms of the thrombosis include: extreme headaches and/or bruises (without actually hurting yourself). Src: my (potentially inaccurate) recollection of my doctor telling me about this.
- wincy 5y ago
  I had the worst headache of my life a few days after getting the J&J vaccine, and went to the emergency room because my wife was worried I’d had Ana aneurysm or something. The ER visit happened the day before the news broke about blood clots and whatnot. The doctor told me it was absolutely unrelated to the vaccine. They did a scan with some contrast dye, said everything looked fine, and discharged me. I couldn’t do strenuous activity for over a week because I’d feel the headache again, almost like a part of the inside of my skull had been scraped, I don’t know how else to describe it.

mapgrep 5y ago

After my J&J shot, for weeks, my legs and feet would frequently feel “asleep.” Especially on waking but often during the day as well. The effect seems to have diminished (and I think mostly resolved) ~6 weeks later. No idea if it’s related to this. (This is on top of the usual reaction of chills/fatigue the first night or two. I will say the fatigue seemed to go on for a while at some modestly higher than usual baseline but I can’t really quantify it or prove it. )

deleted 5y ago

[deleted]

doggodaddo78 5y ago

I had reservations about J&J and AZ because of their complicated nature. I had more confidence in mRNA vaccines (Pfizer and Moderna) as simpler and more elegant to produce the desired immune response. Anytime there are extra steps, there's added risks something can go wrong and cause unknown or horrible side-effects.

stefantalpalaru 5y ago

> an older immune system displays more immune senescence which means that young people exhibit stronger immune reactions than elderly people, and women even stronger than men Non sequitur. Why would women have stronger immune systems than men? Also, if this theoretical mechanism is valid, why is the incidence of thromboembolism the same as before the vaccination campaign? See https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00762-5/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... > all mRNA-based vaccines should represent safe products, because the delivered mRNA will only be translated into surface antigen, without having any possibility to participate in nuclear splice events Not so fast. There's that little detail of lipid nanoparticles being highly inflammatory: https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1.full https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1....

IYasha 5y ago

What a great example of ridiculousness of web 3.0 researchsquare.com loads and then "An unexpected error has occurred." fullscreen. Disabling JS and CSS makes it worse. So un-scientific.