[beagle3]

The safety concerns cannot be resolved yet. Effective - yes. Safe? We won’t know for a while.

Pandemrix, a flu vaccine, caused a notable uptick in narcolepsy in Sweden, Finland and likely the UK. This was not (and could not) be seen in smaller trial populations.

It is not a given that any of the covid vaccines is safe enough. Historically, two cases of rushed vaccines (cutter polio and Gullah barre) were worse than the disease - and these were for diseases worse than covid. Those were 50-60 years ago. Pandemrix was 10-20. I’m not sure we’re that much better on safety now to rush vaccines.

[tialaramex]

If the association between Pandemrix and narcolepsy is because it caused narcolepsy (as with Guillain-Barré it's also plausible the problem is that this is an auto-immune problem and so the vaccine wasn't actually the problem it just highlighted a problem you already had) then the incidence rate was estimated at like 18k patients per case.

So if you give the entire US population a vaccine like that, less than twenty thousand of them develop narcolepsy. As a reminder a quarter million of them already died from COVID-19 and more are dying every day - not to mention the tens of thousands whose cause of death isn't listed as COVID-19 but would not be dead if not for an ongoing pandemic.

Cutter screwed up. No amount of prior safety testing can fix that. Their Polio vaccine had Polio virus in it (to be clear: The traditional Oral Polio Vaccine is supposed to have a "live" virus in it, but the injected vaccine Cutter were selling is not). Obviously nobody is going to test "What happens if we inject children with the Polio virus" because the answer is "Some of them get Polio. Duh" and so no test could have prevented Cutter from screwing up.

I have no idea what you meant by "Gullah barre" the Google results I get are all about Guillain-Barré syndrome, which I mentioned above. Guillain-Barré is not a vaccine, it's a weird auto-immune disorder, and arguably even where it's listed as very rare side effect of a vaccine, that's misleading because it's also a side effect from getting viral infection, so if you avoid vaccination but do get the virus you may get GBS as a result anyway. The human immune system is pretty inscrutable.

[ithkuil]

> less than twenty thousand of them develop narcolepsy. As a reminder a quarter million of them already died from COVID-19 and more are dying every day

I assume the concern is that an unknown unknown means it could cause/trigger/amplify some other disease/condition that may be comparable/worse than the problem it solves.

Cause/effect and morals are hard. Add to the mix a general statistical innumeracy, and some general suspicion about authorities, and it makes it really hard for the general populace to actually weigh the two different options.

I don't think we should dismiss these concerns as just stuff for nutjobs. I've seen otherwise reasonable people having trouble making up their minds about that.

[beagle3]

The association in Sweden is strong enough to say “it does”.

And yes, the mechanism is likely that Pandemrix activated a predisposition. But it was not activated in statistically equivalent kids who did not get Pandemrix.

Why is it so hard to acknowledge that not all vaccines are perfect, and that there’s a risk involved? I am not avtivax. I am pro vaccination. I am anti religious “a vaccine can never be bad” thinking which seem to be prevalent among otherwise rational scientific people.

[abacadaba]

how about compared to the covid risk of a perfectly healthy young adult?

[toyg]

covid risk varies wildly depending on socioeconomic factors. Educated, WFH, small family, stable or low IRL social interaction: pretty low risk. Low-education, multiple in-person jobs, lots of casual social interaction, large family: very high risk. We've seen it very starkly in England. When entire communities are being ravaged by exponentially-growing transmission, it's hard to argue that a vaccine might be worse, because the chances are really minimal.

[mrec]

I think GP is talking about severity of symptoms if you get COVID, rather than your chance of getting it at all.

[i_cannot_hack]

> Historically, two cases of rushed vaccines (cutter polio and Gullah barre) were worse than the disease - and these were for diseases worse than covid.

This is just patently untrue.

The Cutter Incidence gave patients Polio due to an improperly activated virus. While this is bad, it could not be worse than the disease itself - since it is the disease itself, no worse, no less.

Regarding risk of Gullain-Barre syndrome due to vaccination, Wikipedia has this to say: "In fact, natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and getting the vaccination does reduce the risk of GBS overall by lowering the risk of catching influenza." So here I also find it hard to believe the vaccine would be worse than the disease,

I'm also sceptical of the claim that Polio or the 1976 Swine Flu would unambiguously be worse than Covid19. 70% of Polio case have no symptoms, and less than 0.5% cause permanent injury, according to Wikipedia. The 1976 Swine Flu outbreak seems to have caused a few hundred cases and only one death.

[beagle3]

No, the cutter incidence was worse than the disease, because the activated virus was injected into a population, whereas naturally only a tiny part would be exposed at the same level, and the rest would be exposed at a much lower level - that would give them immunity but not disease.

Cutter was, most definitely, much worse than the disease if you look at it from a population perspective.

The 1976 Guilian barre was at least comparable to the flu it was supposed to stop, if not worse. According to https://en.m.wikipedia.org/wiki/1976_swine_flu_outbreak, the disease caused one death and 13 hospitalizations, and an uptick of Giullan barre reports - a disease that more often than not requires hospitalization and sometimes death. I can assure you it caused more than 13 hospitalizations, and - having known two GBS people who made a full recovery - a very long and painful months long process. So, at 50,000,000 immunized - a 1 in 1,000,000 would still be worse than the flu.

I am not anti vax even if HN constantly seems to interpret my comments as such.

I am vaccinated, so are my kids. But whenever I mention that immunizations have risks, I’m treated like a heretic.

Everyone is assuming something like cutter cannot happen again. This is a religious assumption, not a scientific one.

[i_cannot_hack]

> No, the cutter incidence was worse than the disease, because the activated virus was injected into a population, whereas naturally only a tiny part would be exposed at the same level, and the rest would be exposed at a much lower level - that would give them immunity but not disease.

This is a more reasonable assessment, but it is still patently false. According to Wikipedia, 0.04% vaccinations resulted in paralysis in the Cutter Incident, compared to 0.1-0.5% of wild type polio. So the vaccine was 2-10x safer than wild polio. Without vaccinations, virtually all children were infected with polio virus early in life [1], so being administered the defective vaccine was still a lot better than taking a chance with the real disease.

Of course, you are correct regarding the 1976 flu outbreak. If you administer something to a large segment of the healthy population, even a small risk of side-effects will add upp to a large number of cases. If the disease itself turns out to be very rare, as was the case with the flu outbreak, the vaccine itself could cause more damage than the disease even if the disease is much worse.

However, this is clearly not applicable Covid-19, which we already know is spreading very fast and will need to infect a large number of the population before herd immunity is achieved. The situations are simply not comparable at all – even the vaccine from the 1976 flu outbreak would be less risky than the odds of being infected with a serious case of Covid 19 (of which the long term effects are also unknown, to be clear).

> But whenever I mention that immunizations have risks, I’m treated like a heretic.

Mainstream media, healthcare professionals and social media are all worried about the risks of a rushed vaccine. I literally see articles and hear conversations about this several times a month. Nobody is denying that large scale vaccinations have risks.

I'm not criticizing you because I'm against being cautious of vaccination risks. The criticism is that you are spreading false facts and misleading analysis that grossly mischaracterise what the risks of vaccinations really are, both presently and historically.

"Some vaccines can have rare but serious side effects" is a perfectly alright statement. But "Historically, two cases of rushed vaccines (cutter polio and Gullah barre) were worse than the disease - and these were for diseases worse than covid" is just not. Some of it is false and the comparison to Covid19 is misleading.

[1] https://www.ecdc.europa.eu/en/poliomyelitis/facts

[beagle3]

> According to Wikipedia, 0.04% vaccinations resulted in paralysis in the Cutter Incident, compared to 0.1-0.5% of wild type polio.

From https://en.wikipedia.org/wiki/Polio_vaccine#1950%E2%80%93195... : "The Cutter vaccine had been used in vaccinating 200,000 children in the western and midwestern United States.[76] Later investigations showed that the Cutter vaccine had caused 40,000 cases of polio, killing 10.[76]". So, 20% incidence; mentions 250 "paralytic illness", so 0.125% paralysis (no idea where you took the 0.04% - it does not appear in the Wikipedia text).

From https://en.wikipedia.org/wiki/Polio#Paralytic_polio : "In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases." ; So, for children, the incidence of paralysis is 0.1%

Who got the cutter vaccine? Mostly children. See e.g. from https://www.washingtonpost.com/history/2020/04/14/cutter-pol... "By April 30, within forty-eight hours of the recall,” Offit wrote. “Cutter’s vaccine had paralyzed or killed twenty-five children: fourteen in California, seven in Idaho, two in Washington, one in Illinois, and one in Colorado."

So, I just tried to check your numbers, and I couldn't; Could you post references?

But I also wanted to check my memory, and Wikpedia seems to agree with me, Go on, please do check my quotes.

still patently false. pfft. Perhaps false under some assumptions, definitely not "patently false".

[i_cannot_hack]

You are almost certainly using the wrong numbers. According to https://en.wikipedia.org/wiki/Cutter_Laboratories#Cutter_inc... and https://www.nejm.org/doi/full/10.1056/NEJMp048180, the faulty production applied to 120.000 doses of vaccine, which lead to 56 cases of paralysis (0.046%) among vaccinated children. These sources further mention "the exposures led to an epidemic of polio in the families and communities of the affected children, resulting in a further 113 people paralyzed and 5 deaths", which tells me that your number of 250 probably includes cases caused by such transmission. This is of course reasonable when discussing the total damage caused by the vaccine, but this number can not be compared to the incidence of paralysis for a single infection, as you do.

You would also have to include further transmissions caused by wild polio if you would like to make such a comparison.

> still patently false. pfft. Perhaps false under some assumptions, definitely not "patently false".

Even with your own calculation, which is inflated by also including transmission within the community for the vaccine but not for wild polio, the vaccine was very much comparable to wild polio (0.125% versus approx. 0.1%). Without vaccination, polio would usually infect virtually all children. So even with your own inflated assumptions it's false that the vaccine was worse than polio.

So under which assumptions would it not be false?

[beagle3]

> You are almost certainly using the wrong numbers

Take them with wikipedia, not me. I will note, that Wikipedia talks about both Cutter and Wyeth having problems, so it is possible the numbers are a sum of wyeth+cutter which would be compatible with your numbers being cutter only, but in the context of safety vs. polio wouldn't matter.

> You would also have to include further transmissions caused by wild polio if you would like to make such a comparison.

All wild polio numbers include those numbers by default - there actually is no way to get them otherwise, I guess you are saying "you should probably debase by more than 200,000 because of secondary infections". I don't know how to do that, exactly, but it will likely still be similar.

> Even with your own calculation, which is inflated by also including transmission within the community for the vaccine but not for wild polio, the vaccine was very much comparable to wild polio (0.125% versus approx. 0.1%).

With this calculation, the vaccine was 25% worse than the wild type. No error bars, but, that's easily worse, even much worse.

> So under which assumptions would it not be false?

How kind of you to drop "patently". If you didn't mean "patently" false earlier, why did you use that word? twice?

From[0]: "Patently: in a way that is so obvious that no one could disagree.". It's nice of you to finally bring sources, but even these sources don't make it "patently" false, given that they disagree with the sources I gave (which, I concede, reference more than just the safety of the Cutter incident which I originally mentioned, but which are definitely the subject matter under discussion)

[0] https://www.macmillandictionary.com/dictionary/british/paten...

[roenxi]

On the one hand I tend to agree, and all my expectations for this vaccine are positive. The medical industry tends to be paranoid to a level that exceeds rationality and even if they dropped their standards for this that should only get them down to "conservative and rather safe" levels of caution.

On the other, a cursory search says the current record for fastest developed vaccine was mumps at 4 years. So this is a vaccine setting new milestones, and there is a risk that not all of them will be positive. I'd rather be a little late to be vaccinated than a little early, especially being in a lower risk demographic.

[taejo]

I'm not an expert by any means, but I do know that a lot of the speed comes from moving along the CHEAP-FAST side of the CHEAP-FAST-SAFE triangle, without necessarily changing anything on the FAST-SAFE axis. In particular, governments paid for the companies to start producing enough vaccines for phase 3 trials before phase 1 was complete, while normally drug companies would wait for phase 1 to be completed before preparing for phase 2 for economic reasons.

[beagle3]

BiondVax recently finished their phase 3 trial of a universal flu vaccine. It was 15 years in the making. Science was (still is solid). Phase 3 took two years to account for ADE and other safety issues.

At the 1-year mark, everything looked perfect. At the towo years mark (original endpoint) the conclusion was that while it was safe, it offered statistically insignificant protection.

Properly designed tests need those 2 years, at the very least. The “SAFE” confidence axis was compromised. Whether or nit it is justified is what we’re discussing here.

[fergal_reid]

I'm very pro-vaccine, and not disagreeing with your conclusions, but your logic leaves out the consideration that the natural risk also depends on catching the disease, whereas the vaccine is administered systematically.

[jjk166]

Well the odds of people getting the flu are pretty high

[disabled]

I have had Guillain-Barre Syndrome (not due to a vaccine). No matter what, I still always get my vaccines and make sure that I am up to date and never late on any of them.

Sure, having Guillain-Barre is scary, but it is something that you can make a full recovery from.

It is never an excuse NOT to get a vaccine, unless you actually know that you got Guillain-Barre Syndrome from a vaccine. That is a discussion between that particular patient and their neuromuscular neurologist. In that case, you do not get the flu vaccine any longer because it can cause you to experience Guillain-Barre Syndrome again.

But, this really is an isolated situation that can be categorized as very rare and the general public should always get their vaccines.

If you catch the flu, it can absolutely trigger Guillain-Barre Syndrome, and would be far more likely to trigger Guillain-Barre Syndrome than the flu vaccine itself. If you get the flu and had the flu vaccination, it typically makes the flu illness less worse, making you less likely to get something like Guillain-Barre Syndrome.

There are lots of infectious agents that can trigger Guillain-Barre Syndrome, so it is wise to get your vaccines to prevent them as much as possible. They prevent serious infections, at minimum, which would help prevent Guillain-Barre Syndrome.

I also have the long term variant of Guillain-Barre Syndrome, known as Chronic Inflammatory Demyelinating Polyneuropathy, which is in pharmaceutical remission due to me taking subcutaneous immunoglobulin twice a week for 3 hours each time.

What I am saying is that while all of this sounds rare and devastating, it’s treatable. Not only that, you’re more likely to get Guillain-Barre Syndrome from a bad case of the flu than from a flu shot.

[acqq]

2011:

https://www.who.int/vaccine_safety/committee/topics/influenz...

“Even at this stage, it does not appear that narcolepsy following vaccination against pandemic influenza is a general worldwide phenomenon, as no excess of narcolepsy has been reported from several other European states where Pandemrix was used, or from Canada where a pandemic vaccine similar to pandemrix was used. This complicates interpretation of the findings in Finland and Sweden. It seems likely that some as yet unidentified additional factor was operating in Sweden and Finland. The findings from the VAESCO project and further investigations in Finland and Sweden, may help clarify the determinants of any increased risk of narcolepsy, which currently appears to be restricted to the months following vaccination and by age group and country.”

What’s certainly true that for some effects to be observable, millions have to be vaccinated first.

2013:

https://www.reuters.com/article/us-narcolepsy-vaccine-pandem...

“In total, the GSK shot was given to more than 30 million people in 47 countries during the 2009-2010 H1N1 swine flu pandemic.”

“Independent teams of scientists have published peer-reviewed studies from Sweden, Finland and Ireland showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between seven and 13 times higher for children who had Pandemrix than for their unvaccinated peers.”

“Europe’s drugs regulator has ruled Pandemrix should no longer be used in people aged under 20.”

[542354234235]

> Pandemrix, a flu vaccine, caused a notable uptick in narcolepsy in Sweden, Finland and likely the UK.

"The increased risk of narcolepsy due to vaccination was 1 in 18400 or 0.005%."[1] Considering the fatality and long term disability rate of Covid, and the way testing and safety protocols are done for vaccines, I don't really see how there could be an unknown and unseen risk that would outweigh the risk of contracting Covid.

https://en.wikipedia.org/wiki/Pandemrix#Side_effects

[beagle3]

The risk of death in kids without underlying diseases is is approximately 0. It is not clear that giving (e.g. in the US) 30,000 of these kids narcolepsy is reasonable.

It might be, but it’s not open and shut.

[Exmoor]

As far as I know, none of the COVID19 vaccines have been tested on children under 12 or are currently planned on being given to children.

Additionally, it's not as if the average vaccine has a 0.005% chance of giving you narcolepsy. That figure was for the one vaccine in one country which appears to be the only example in most people's living memory of a vaccine possibly causing long-term side effects (it's not even proven the vaccine was the cause). There have been tens of billions of vaccines given during this time period and this is the only example where there may have been long term side effects.

[beagle3]

I've also mentioned the cutter polio vaccine and the 1976 swine flu vaccine which seems to have caused an uptick of GBS.

> There have been tens of billions of vaccines given during this time period and this is the only example where there may have been long term side effects.

No, there are other examples, the other two I just mentioned are from memory, I suspect if I go research I will find more (I don't have the time). You know what else is common to those other two cases? They were rushed (pandemrix wasn't AFAIK).

SARS-Cov-2 vaccines were all rushed, and the safety protocols used to confidently ascertain those billions of vaccines were NOT followed - The standard is to wait 2-4 years to see that there's no ADE or other issues.

I am pro-vaccination. I don't understand why it is hard to acknowledge and discuss the risk profile of vaccines - they re not risk free. Excuse me if I don't automatically think a rushed vaccine is perfectly safe.

[Exmoor]

> I've also mentioned the cutter polio vaccine and the 1976 swine flu vaccine which seems to have caused an uptick of GBS.

That Polio vaccine wasn't a side effect of the vaccine though, it was an issue with people accidently getting injected with a live virus. Since no live virus is even remotely involved in any COVID19 vaccines it has zero relevance here. Even if they were, we have 60+ years of history with no similar incidents since then.

> I suspect if I go research I will find more

You really won't. I've been reading about this extensively during this period and those are the only examples where there may have been long term effects that anyone can point to.

I qualified my original comment with "in most people's living memory" and didn't include the '76 swine flu vaccine because, frankly, I don't think pointing to an issue that happened 44 years ago in a field that has seen pretty significant technological advancement in knowledge, methods, and manufacturing processes really makes sense.

> why it is hard to acknowledge and discuss the risk profile of vaccines

My issue is not that there's isn't some theoretical risk, it's that it just isn't put in context of how minute it is. In all likelihood your risk of facing long term effects from a car accident happening on your way to get vaccinated are higher than anything that could happen from the vaccine. And both those risks are, of course, many orders of magnitude less than your chance of suffering long-term effects from catching COVID19.

[beagle3]

> Since no live virus is even remotely involved in any COVID19 vaccines it has zero relevance here.

Your omnipotent knowledge is inspiring. We have absolutely zero years of experience with RNA based vaccines. We had incidents with vaccines, not of the same kind. Ergo, there's a non zero probability we will have incidents in the future, by any reasonable inference.

> I qualified my original comment with "in most people's living memory" and didn't include the '76 swine flu vaccine because, frankly, I don't think pointing to an issue that happened 44 years ago in a field that has seen pretty significant technological advancement in knowledge, methods, and manufacturing processes really makes sense.

That's really painting a target where your arrow landed. Most people's living memory does not include e.g. the 1918 pandemic or the bubonic plague, or atomic bombs, or thousands of other things we're proactively defending against and of which we have better understanding but are still an issue. If "living memory" is your criterion ... well, I wouldn't describe it as anything but completely arbitrary.

Within living memory you have totally understandable and preventable things like Fukushima, the nestle mother milk fiasco in Africa, and others. We had enough understanding to stop all of them, and yet they happened. Every single SARS-COV-2 vaccine manufacturer has gotten government immunity from future claims, which aligns their incentive differently compared to vaccines they have produced in the past. They have become too big/important to sue - much like e.g. the fukushima reactor operator. Given this distinctly different incentive structure, rushed schedule, novel RNA delivery system - your belief that the past is a good predictor of the future is unscientific (at the very least, unbayesian without a ton of nontrivial priors you don't bother stating).

> And both those risks are, of course, many orders of magnitude less than your chance of suffering long-term effects from catching COVID19.

Ah, about that. Do you have any actual data about that? Because the best summary of "long covid" evidence I found was written by an MD, is summarized here[0], and can further be summarized by the word "lacking". I spent a lot of time looking for actual data about long covid (not anecdotes), and this summary is better than what I was able to find myself (but I do urge you to read it - do introduce it to your "living memory").

[0] https://sebastianrushworth.com/2020/11/17/what-is-long-covid...

[snowwolf]

I wonder if because the Oxford vaccine has taken an already tested and approved vaccine approach it has a higher chance of safety than the other 2 which use a new approach that has never been approved by regulators before.

[Brakenshire]

Is there precedent for the Oxford vaccine? I didn’t realise that.

[DennisP]

FTA: "The Oxford vaccine (ChAdOx1 nCoV-19) is made from a virus, which is a weakened version of a common cold virus (adenovirus), that has been genetically changed so that it is impossible for it to grow in humans. Adenovirus vaccines have been researched and used extensively for decades"