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I'm vaccinated but I think it's hindsight bias to say the mRNA vaccines are obviously safe. We had to wait for clinical trials to show that. There has been a gr

I'm vaccinated but I think it's hindsight bias to say the mRNA vaccines are obviously safe. We had to wait for clinical trials to show that. There has been a great deal of research and development on the delivery of the mRNA, what kind of molecule to wrap it in, for example. Additionally, and someone correct me if I'm wrong, but with e.g. the Spanish Flu, the morbidity was not from the flu, per se, but the immune response to it (cytokine storm, which I believe is implicated in Covid somewhat, too). If that's the case, could the proteins coded by the mRNA potentially have kicked off such a response? I know we see that it doesn't, but could it have?

radpl 5y ago
Not really, because your muscle where you got shot was mostly producing spike proteins. When you get the virus, it replicates in your lungs, immunity response happens there and if it’s too strong, it can destroy your lung tissue and cause death.
outworlder 5y ago
> If that's the case, could the proteins coded by the mRNA potentially have kicked off such a response? Why would they? And more specifically, why would they cause lung issues? Because that's the main problem with COVID. The virus like to bind to cells that have a specific receptors, with the vast majority contained in lung tissue. You would expect to see major damage near the injection site if your cytokine storm theory had weight, but not much else. If there is a mechanism that will cause side effects on mRNA vaccines, then such mechanism will also be presented in the virus. Except it's a localized, self-limited amount, as mRNA cannot replicate. Viruses can.
- jfkgktjjj 5y ago
  > If there is a mechanism that will cause side effects on mRNA vaccines, then such mechanism will also be presented in the virus. You're forgetting about the lipids the vaccine mRNA is put into. One big reason it took so long to create mRNA vaccines was finding a suitable lipid mix. They need to have a specific property, they need to be electrically charged in a certain way, and pretty much all lipids with that property are extremely toxic. The equivalent lipids in the virus don't have this problem because they come from the human cell membrane and they use the spike protein to fuse. Since the vaccine doesn't have a spike protein, it needs that special charge property to be able to spill it's mRNA. The question now is, if it took sooo long to find those lipids, just what the safety margin on them is? https://pubmed.ncbi.nlm.nih.gov/27433582/ https://pubmed.ncbi.nlm.nih.gov/27433582/ https://cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8 https://cen.acs.org/pharmaceuticals/drug-delivery/Without-li...
  - deleted 5y ago
    [deleted]
  - sergiosgc 5y ago
    Just for reference, for those that won't read the articles you link to: The conclusion of the article is that these lipids are safe, with a recommendation for further study. The article is from 2016, no ill effects were found since then
  - kaba0 5y ago
    While medicine doesn’t work like this, but what is the proposed mechanism from any sort of side effect from the minuscule amount of lipids, probably largely derived from already known substances?
  - zaarn 5y ago
    Consider how little is actually injected into the human body (sub milligram dose mixed with saline solution), even if it was toxic, I doubt it would have any effect at this scale. And btw, there is no difference between lipids we can make and lipids that our cells make. It's the same chemical composition.
- losvedir 5y ago
  > Except it's a localized, self-limited amount, as mRNA cannot replicate. Well, hence my question about cytokine storm, since by definition that's an out of control feedback loop prompted by other cytokines and not the underlying virus any more. My question was about whether it's possible that just the spike protein could conceivably have induced that effect. Good point about the localization of it. Though, I do feel like I read somewhere you see the Spike proteins mostly around the shoulder and in the liver, so it does travel through the blood somewhat. Also, I was under the misunderstanding that cytokines were part of the adaptive immune system, and hence produced – I think? – in the bone marrow. If that were true, it wouldn't matter so much where the antigens were, since the B/T-Cells (getting confused on which is which) are produced elsewhere and have to make their way there anyway. And if that's the case, they'd be visiting the lungs. And, being adaptive, I thought it was something about the shape of covid and hence the antibodies that kicked off the storm in the lungs, and not necessarily the quantity or prevalence of the antigen in the lungs. But, turns out it's part of the innate immune system, and seems like cytokines are mostly produced near the infection itself.
MikeKusold 5y ago
They are not "obviously safe". The mRNA vaccines just had an article today that exposed a link to heart inflammation. The AstraZeneca vaccine also has some side effects that didn't show up in their abbreviated trials. I understand why someone would be hesitant to get a vaccine that only has Emergency Use Authorization. That said, I personally believe that the benefits outweigh the potential side-effects. If I weren't already vaccinated this news would not have have changed my decision to get a mRNA vaccine. "Heart inflammation in young men higher than expected after Pfizer, Moderna vaccines -U.S. CDC" - https://www.reuters.com/world/us/cdc-heart-inflammation-cases-ages-16-24-higher-than-expected-after-mrna-covid-19-2021-06-10/ https://www.reuters.com/world/us/cdc-heart-inflammation-case...
- deleted 5y ago
  [deleted]
  - fastball 5y ago
    Eh, my problem is that it's a bit of a tragedy of the commons situation. Yes, of course it's the best case scenario for an individual if 1. we eradicate COVID 2. they don't need to get vaccinated. The problem is if we allow that sort of mentality to propagate unchallenged, then everyone wants to be one of the select few who take on zero personal risk but see all the benefit of an immunized herd. And then you don't end up with an immunized herd and society loses, tragedy-of-the-commons style.
- jonhohle 5y ago
  I'm concerned, especially in the tech community, that there is so much aggravation toward a group that wants more data before making a decision that could have long term repercussions. The CDC has a page describing past vaccine safety issues, the most recent being 2013[0]. Errors include unexpected side effects or complicates and manufacturing issues. The treatment being offered is unlike any other mainstream protocol, has not completed the FDA approval process that every other vaccine that's given to the general population (in the US) has gone through. Add to that counter-intuitive advice being given by medical professionals. When I was young, I had chicken pox. I was never offered the vaccine that my children have received. However, previously infected people are being urged to undergo this treatment. I could do the primary research to determine _why_ that is the case, or those urging everyone to participate can explain clearly why it's different this time. I don't like the language chosen, which, to me, obscures the idea that what is being offered is like a yearly flu vaccine or any other dead/disabled/controlled viral vaccine. I've read that there are vaccines for SARS-CoV2 that are similar to what normally comes to mind, but they are not available in my country. mRNA research is awesome. The technique is very cool, but beyond the theoretical best case scenario, what are the failure cases for these treatments? What if the mRNA is damaged along the way. What if there are unknown issue with the delivery mechanism. Ultimately, I am the primary income for our family and in a not-at-risk category if I were to get infected. At this time, I've decided that is a safer position for my family. I'm hoping that as FDA approval is granted and longer term affects are well known that I'll be comfortable going forward, but at this point I am not. I'm not anti-vax, but not keen to be an early adopter for new treatment option when I'm not at danger of what I'm being protected from. There's the additional argument about protecting those that can't be vaccinated, but I'm happy to follow other hygiene protocols that have been used in practice for much longer. 0 - https://www.cdc.gov/vaccinesafety/concerns/concerns-history.html https://www.cdc.gov/vaccinesafety/concerns/concerns-history....
kaba0 5y ago
> the Spanish Flu, the morbidity was not from the flu, per se, but the immune response to it Sorry for being pedantic, but it’s the same as “you don’t die from being shot, but from the resulting blood loss”. Also, we did absolutely have clinical trials — only some aspect of it was allowed to begin sooner than it otherwise would have due to the urgency. Also, the mRNA tech was in development for a decade now.
- losvedir 5y ago
  > Sorry for being pedantic, but it’s the same as “you don’t die from being shot, but from the resulting blood loss”. I think I wasn't clear then. With the Spanish Flu, the virus took hold in the host and multiplied. As part of the immune response, the body released cytokines, which normally help with the situation. But for reasons I don't understand, the Spanish Flu often prompted a "cytokine storm", which is an uncontrolled and excessive release of these molecules, even after the virus was cleared. Ultimately, it was these cytokines, not the virus, that overwhelmed the body and killed the patient. So what we saw with the Spanish Flu was that younger people with stronger immune systems, died more than older people with weaker ones. But the relevance here is that the mRNA vaccines inject a ton of mRNA to induce the body to produce Spike protein, a piece of Covid, in order to teach the adaptive immune system to recognize it and produce antibodies. And so my question is, could it have been the case that these Spike proteins would induce a cytokine storm? (We see now that they don't, but I'm not sure that was clear a priori.) In other words, I think it's important to draw the distinction between the "gun shot" and the "blood loss". With Spanish Flu, a lot of the mortality came from the blood loss. However, with Covid, it appears the "gun shot" does more damage (i.e. patients who die form Covid, continue to have high viral loads; it's not a case that the immune system is what kills them). But none of this was clear in advance. > Also, we did absolutely have clinical trials Yes, I said that.

radpl 5y ago

Not really, because your muscle where you got shot was mostly producing spike proteins. When you get the virus, it replicates in your lungs, immunity response happens there and if it’s too strong, it can destroy your lung tissue and cause death.

outworlder 5y ago

> If that's the case, could the proteins coded by the mRNA potentially have kicked off such a response? Why would they? And more specifically, why would they cause lung issues? Because that's the main problem with COVID. The virus like to bind to cells that have a specific receptors, with the vast majority contained in lung tissue. You would expect to see major damage near the injection site if your cytokine storm theory had weight, but not much else. If there is a mechanism that will cause side effects on mRNA vaccines, then such mechanism will also be presented in the virus. Except it's a localized, self-limited amount, as mRNA cannot replicate. Viruses can.

jfkgktjjj 5y ago
> If there is a mechanism that will cause side effects on mRNA vaccines, then such mechanism will also be presented in the virus. You're forgetting about the lipids the vaccine mRNA is put into. One big reason it took so long to create mRNA vaccines was finding a suitable lipid mix. They need to have a specific property, they need to be electrically charged in a certain way, and pretty much all lipids with that property are extremely toxic. The equivalent lipids in the virus don't have this problem because they come from the human cell membrane and they use the spike protein to fuse. Since the vaccine doesn't have a spike protein, it needs that special charge property to be able to spill it's mRNA. The question now is, if it took sooo long to find those lipids, just what the safety margin on them is? https://pubmed.ncbi.nlm.nih.gov/27433582/ https://pubmed.ncbi.nlm.nih.gov/27433582/ https://cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8 https://cen.acs.org/pharmaceuticals/drug-delivery/Without-li...
- deleted 5y ago
  [deleted]
- sergiosgc 5y ago
  Just for reference, for those that won't read the articles you link to: The conclusion of the article is that these lipids are safe, with a recommendation for further study. The article is from 2016, no ill effects were found since then
- kaba0 5y ago
  While medicine doesn’t work like this, but what is the proposed mechanism from any sort of side effect from the minuscule amount of lipids, probably largely derived from already known substances?
- zaarn 5y ago
  Consider how little is actually injected into the human body (sub milligram dose mixed with saline solution), even if it was toxic, I doubt it would have any effect at this scale. And btw, there is no difference between lipids we can make and lipids that our cells make. It's the same chemical composition.
losvedir 5y ago
> Except it's a localized, self-limited amount, as mRNA cannot replicate. Well, hence my question about cytokine storm, since by definition that's an out of control feedback loop prompted by other cytokines and not the underlying virus any more. My question was about whether it's possible that just the spike protein could conceivably have induced that effect. Good point about the localization of it. Though, I do feel like I read somewhere you see the Spike proteins mostly around the shoulder and in the liver, so it does travel through the blood somewhat. Also, I was under the misunderstanding that cytokines were part of the adaptive immune system, and hence produced – I think? – in the bone marrow. If that were true, it wouldn't matter so much where the antigens were, since the B/T-Cells (getting confused on which is which) are produced elsewhere and have to make their way there anyway. And if that's the case, they'd be visiting the lungs. And, being adaptive, I thought it was something about the shape of covid and hence the antibodies that kicked off the storm in the lungs, and not necessarily the quantity or prevalence of the antigen in the lungs. But, turns out it's part of the innate immune system, and seems like cytokines are mostly produced near the infection itself.

MikeKusold 5y ago

They are not "obviously safe". The mRNA vaccines just had an article today that exposed a link to heart inflammation. The AstraZeneca vaccine also has some side effects that didn't show up in their abbreviated trials. I understand why someone would be hesitant to get a vaccine that only has Emergency Use Authorization. That said, I personally believe that the benefits outweigh the potential side-effects. If I weren't already vaccinated this news would not have have changed my decision to get a mRNA vaccine. "Heart inflammation in young men higher than expected after Pfizer, Moderna vaccines -U.S. CDC" - https://www.reuters.com/world/us/cdc-heart-inflammation-cases-ages-16-24-higher-than-expected-after-mrna-covid-19-2021-06-10/ https://www.reuters.com/world/us/cdc-heart-inflammation-case...

deleted 5y ago
[deleted]
- fastball 5y ago
  Eh, my problem is that it's a bit of a tragedy of the commons situation. Yes, of course it's the best case scenario for an individual if 1. we eradicate COVID 2. they don't need to get vaccinated. The problem is if we allow that sort of mentality to propagate unchallenged, then everyone wants to be one of the select few who take on zero personal risk but see all the benefit of an immunized herd. And then you don't end up with an immunized herd and society loses, tragedy-of-the-commons style.
jonhohle 5y ago
I'm concerned, especially in the tech community, that there is so much aggravation toward a group that wants more data before making a decision that could have long term repercussions. The CDC has a page describing past vaccine safety issues, the most recent being 2013[0]. Errors include unexpected side effects or complicates and manufacturing issues. The treatment being offered is unlike any other mainstream protocol, has not completed the FDA approval process that every other vaccine that's given to the general population (in the US) has gone through. Add to that counter-intuitive advice being given by medical professionals. When I was young, I had chicken pox. I was never offered the vaccine that my children have received. However, previously infected people are being urged to undergo this treatment. I could do the primary research to determine _why_ that is the case, or those urging everyone to participate can explain clearly why it's different this time. I don't like the language chosen, which, to me, obscures the idea that what is being offered is like a yearly flu vaccine or any other dead/disabled/controlled viral vaccine. I've read that there are vaccines for SARS-CoV2 that are similar to what normally comes to mind, but they are not available in my country. mRNA research is awesome. The technique is very cool, but beyond the theoretical best case scenario, what are the failure cases for these treatments? What if the mRNA is damaged along the way. What if there are unknown issue with the delivery mechanism. Ultimately, I am the primary income for our family and in a not-at-risk category if I were to get infected. At this time, I've decided that is a safer position for my family. I'm hoping that as FDA approval is granted and longer term affects are well known that I'll be comfortable going forward, but at this point I am not. I'm not anti-vax, but not keen to be an early adopter for new treatment option when I'm not at danger of what I'm being protected from. There's the additional argument about protecting those that can't be vaccinated, but I'm happy to follow other hygiene protocols that have been used in practice for much longer. 0 - https://www.cdc.gov/vaccinesafety/concerns/concerns-history.html https://www.cdc.gov/vaccinesafety/concerns/concerns-history....

kaba0 5y ago

> the Spanish Flu, the morbidity was not from the flu, per se, but the immune response to it Sorry for being pedantic, but it’s the same as “you don’t die from being shot, but from the resulting blood loss”. Also, we did absolutely have clinical trials — only some aspect of it was allowed to begin sooner than it otherwise would have due to the urgency. Also, the mRNA tech was in development for a decade now.

losvedir 5y ago
> Sorry for being pedantic, but it’s the same as “you don’t die from being shot, but from the resulting blood loss”. I think I wasn't clear then. With the Spanish Flu, the virus took hold in the host and multiplied. As part of the immune response, the body released cytokines, which normally help with the situation. But for reasons I don't understand, the Spanish Flu often prompted a "cytokine storm", which is an uncontrolled and excessive release of these molecules, even after the virus was cleared. Ultimately, it was these cytokines, not the virus, that overwhelmed the body and killed the patient. So what we saw with the Spanish Flu was that younger people with stronger immune systems, died more than older people with weaker ones. But the relevance here is that the mRNA vaccines inject a ton of mRNA to induce the body to produce Spike protein, a piece of Covid, in order to teach the adaptive immune system to recognize it and produce antibodies. And so my question is, could it have been the case that these Spike proteins would induce a cytokine storm? (We see now that they don't, but I'm not sure that was clear a priori.) In other words, I think it's important to draw the distinction between the "gun shot" and the "blood loss". With Spanish Flu, a lot of the mortality came from the blood loss. However, with Covid, it appears the "gun shot" does more damage (i.e. patients who die form Covid, continue to have high viral loads; it's not a case that the immune system is what kills them). But none of this was clear in advance. > Also, we did absolutely have clinical trials Yes, I said that.