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Does anyone understand why the FDA and other experts seem very unconcerned about long term side effects? The safety profile in the 0-2 month timeframe is very

Does anyone understand why the FDA and other experts seem very unconcerned about long term side effects? The safety profile in the 0-2 month timeframe is very easy to understand: they tested it, so they have actual data. But it seems for longer than 2 or 3 months you would need to make an argument based on animal trials or just biological reasoning. But I can't find anyone talking about it at all.

TheAdamAndChe 6y ago
They are concerned, but it's a balancing act. COVID itself is a new virus with unknown long term side effects, and it's killing millions while causing massive economic harm triggering political destabilization in some areas. The vaccine is new and may cause issues, but current data doesn't indicate it will cause issues and it prevents death and sickness by COVID very effectively.
throw9678 6y ago
As mentioned in the Nature article and in another poster's comment[1], MRNA vaccines have been known for a while now (decade+ ?), and studied on animals, with some limited phase I / phase II human studies. But nobody's gone through a full phase III before covid hit, so that kind of a wide fan-out is new and exceptional because of the emergency nature of the disease. But I don't think they're unconcerned. I think it's a combination of lack of decades-long longitudinal studies, and also that previous phase I / II studies haven't throw up significant red flags. [1] https://news.ycombinator.com/item?id=25403560 https://news.ycombinator.com/item?id=25403560
- reader_1000 6y ago
  > But nobody's gone through a full phase III before covid hit, Do you know why nobody did not conduct phase III before? Is it because of safety concerns or lack of necessity since concerned disease disappeared?
  - detaro 6y ago
    AFAIK some of the breakthroughs in the delivery mechanisms are relatively new. Some of the companies now making a covid vaccine were talking about running a trial for a flu vaccine in the next few years, but obviously that was far less urgent and all the steps (getting permission, getting participants, actually running the study without "unlimited" money, ...) would take longer. (mRNA would be a good candidate for a flu vaccines because they are fast to produce, which in theory reduces the amount of guessing needed to make the "right" flu vaccine for the year, but of course a) flu vaccines already are a thing even if sometimes wrong and b) a flu vaccine isn't given as high priority overall)
Exmoor 6y ago
In addition to your other responses, I'll add this. There's not really a plausible mechanism that could cause problems to happen long after the fact. Although it sounds exotic, the mRNA vaccine is just using the same process every cold or flu you've ever had used, but in a more limited way since the proteins created by the vaccine cannot reproduce. By 2 months all traces of vaccine are long gone and you're just left with an immune system trained to fight COVID (just like millions of people have already had happen naturally). So, while everybody has their eyes open, nobody can really explain the mechanism where something might happen.
- crazydoggers 6y ago
  > There's not really a plausible mechanism that could cause problems to happen long after the fact. Well there are some limited circumstances, but I don’t think they justify not going forward with the vaccine. For instance there is a possibility in some individuals that the mRNA itself (not just the spike protein) as well as the lipid encasing it to protect it and transport it into the cell can cause an immune response. It’s theoretically possible that in some individuals that could result in auto immune responses to other forms of messenger RNA in their cells. [1] 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ From the article “A possible concern could be that some mRNA-based vaccine platforms induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity”
  - reader_1000 6y ago
    Compared to old traditional vaccines, is mRNA-based vaccine safer considering long term side effects?
mchusma 6y ago
They discussed this in the approval meeting. There was only one case ever in any vaccine or trial of a side effect showing up after 6 weeks, it was over 50 years ago in a live virus polio vaccine on an immunocompromised person. Given the many billions of vaccines given of various types, it is about as close to certain as we get in this world to not expecting long term side effects ever. The reason they aren't concerned about it is for good reason, not because they "haven't looked into it". You have to look at relative risk. This decision to lift the total ban on this vaccine was probably the easiest decision the FDA ever had to make. This one isn't even a question. Now they just have to lift the ban on the rest. The standard for EUA is supposed to be "net expected benefit", which they are not following. They are currently only approving EUA when they hit "no conceivable downside", which is a too high standard.
- ars 6y ago
  > There was only one case ever in any vaccine or trial of a side effect showing up after 6 weeks That is not true: https://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashield-historical.htm https://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashiel... It was approved August 1998 and removed from market October 1999 - more than a year later. Edit: Oh, I see what you are saying - the intussusception happened within 2 weeks of receiving the vaccine. But that's not really comforting, if it took more than a year to understand that it was linked to the vaccination.

TheAdamAndChe 6y ago

They are concerned, but it's a balancing act. COVID itself is a new virus with unknown long term side effects, and it's killing millions while causing massive economic harm triggering political destabilization in some areas. The vaccine is new and may cause issues, but current data doesn't indicate it will cause issues and it prevents death and sickness by COVID very effectively.

throw9678 6y ago

As mentioned in the Nature article and in another poster's comment[1], MRNA vaccines have been known for a while now (decade+ ?), and studied on animals, with some limited phase I / phase II human studies. But nobody's gone through a full phase III before covid hit, so that kind of a wide fan-out is new and exceptional because of the emergency nature of the disease. But I don't think they're unconcerned. I think it's a combination of lack of decades-long longitudinal studies, and also that previous phase I / II studies haven't throw up significant red flags. [1] https://news.ycombinator.com/item?id=25403560 https://news.ycombinator.com/item?id=25403560

reader_1000 6y ago
> But nobody's gone through a full phase III before covid hit, Do you know why nobody did not conduct phase III before? Is it because of safety concerns or lack of necessity since concerned disease disappeared?
- detaro 6y ago
  AFAIK some of the breakthroughs in the delivery mechanisms are relatively new. Some of the companies now making a covid vaccine were talking about running a trial for a flu vaccine in the next few years, but obviously that was far less urgent and all the steps (getting permission, getting participants, actually running the study without "unlimited" money, ...) would take longer. (mRNA would be a good candidate for a flu vaccines because they are fast to produce, which in theory reduces the amount of guessing needed to make the "right" flu vaccine for the year, but of course a) flu vaccines already are a thing even if sometimes wrong and b) a flu vaccine isn't given as high priority overall)

Exmoor 6y ago

In addition to your other responses, I'll add this. There's not really a plausible mechanism that could cause problems to happen long after the fact. Although it sounds exotic, the mRNA vaccine is just using the same process every cold or flu you've ever had used, but in a more limited way since the proteins created by the vaccine cannot reproduce. By 2 months all traces of vaccine are long gone and you're just left with an immune system trained to fight COVID (just like millions of people have already had happen naturally). So, while everybody has their eyes open, nobody can really explain the mechanism where something might happen.

crazydoggers 6y ago
> There's not really a plausible mechanism that could cause problems to happen long after the fact. Well there are some limited circumstances, but I don’t think they justify not going forward with the vaccine. For instance there is a possibility in some individuals that the mRNA itself (not just the spike protein) as well as the lipid encasing it to protect it and transport it into the cell can cause an immune response. It’s theoretically possible that in some individuals that could result in auto immune responses to other forms of messenger RNA in their cells. [1] 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/ From the article “A possible concern could be that some mRNA-based vaccine platforms induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity”
- reader_1000 6y ago
  Compared to old traditional vaccines, is mRNA-based vaccine safer considering long term side effects?

mchusma 6y ago

They discussed this in the approval meeting. There was only one case ever in any vaccine or trial of a side effect showing up after 6 weeks, it was over 50 years ago in a live virus polio vaccine on an immunocompromised person. Given the many billions of vaccines given of various types, it is about as close to certain as we get in this world to not expecting long term side effects ever. The reason they aren't concerned about it is for good reason, not because they "haven't looked into it". You have to look at relative risk. This decision to lift the total ban on this vaccine was probably the easiest decision the FDA ever had to make. This one isn't even a question. Now they just have to lift the ban on the rest. The standard for EUA is supposed to be "net expected benefit", which they are not following. They are currently only approving EUA when they hit "no conceivable downside", which is a too high standard.

ars 6y ago
> There was only one case ever in any vaccine or trial of a side effect showing up after 6 weeks That is not true: https://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashield-historical.htm https://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashiel... It was approved August 1998 and removed from market October 1999 - more than a year later. Edit: Oh, I see what you are saying - the intussusception happened within 2 weeks of receiving the vaccine. But that's not really comforting, if it took more than a year to understand that it was linked to the vaccination.