Btw .. I think public health needs to start educating people on how these things work in order to get high coverage. I am alarmed at the number of highly educated people I know who seem suspicious. This fear is just borne by a lack of understanding and can be corrected IMHO.

In other words, its May 2020 and you have the option to ban vaccines or allow vaccines for the elderly, what do you pick?

We know the following about vaccines generally: -Vaccines have an extremely high success rate, 33% of vaccines make it through all trials to approval. 50% after phase 1 is complete. -The worst vaccine side effect ever is widely considered to be the swine flu vaccine from 60 years ago, where 1 in 100,000 got GBS, or Pandemrix, where 1 in 18400 got narcolepsy. (1)(2) -Vaccine candidates have 85% chance of making it from phase III to approved (phase III is supposed to be the efficacy check), in other words we expect about a 15% chance that the vaccine is not effective, most of the tests are about safety.

We know the following about COVID: -Unknown long term side effects, reasonably likely to be worse than the worst vaccines ever, but unknown. -The IFR for those over 75 is about 4.6% now(1). Earlier in the pandemic it was about 11.6%(2). -If you assume that people have a 10% chance of contracting the disease, you can say that those over 75 would have approximately a 0.46% chance of dying (4.6 in 1,000 dead) if they don't get the vaccine. This seems to be a conservative estimate.

So if you have to decide whether to ban a vaccine or not in May 2020, and you assume with 100% confidence that this vaccine was tied for the "worst side effects ever", for example it turns out to be as bad as Pandemrix, then you would expect 1 in 18400 to get something like narcolepsy if you give them the vaccine.

Using the IFR and 10% number above, you assume that not giving the vaccine would leave 84.64 dead for the same population. (85x by volume).

I don't know your opinion of "how much worse is death versus narcolepsy?". If you believe death is 10x worse than narcolepsy, then by severity and volume, taking a vaccine with the worst side effects ever would seem about 850x better than not taking it (in elderly populations). Earlier in the pandemic, when IFRs were over 2x as bad, this was well over 1,000x better.

I mean, the numbers so dramatically favor vaccination that I don't get it at all. Why is this not approved already? Why does it take the FDA 3 weeks to even discuss the matter of approval when this made sense to approve in May? Why did all governments opt to ban the vaccines versus allow them?

Sources: (1) https://en.wikipedia.org/wiki/Pandemrix (2) https://www.cdc.gov/vaccinesafety/concerns/concerns-history.... (3) https://www.medrxiv.org/content/10.1101/2020.07.23.20160895v... (4) https://www.nature.com/articles/d41586-020-02483-2

I read recently that in some European country (was it Germany?) the willingness to vaccinate against COVID-19 went down from 80% to 60%. With these numbers policy makers will have a hard time convincing the broad population that they can rely on a due process and be safe. In the meantime there is a proliferation of false information and fake news, while in the past there was not much media coverage of significant side effects from a rushed swine flu vaccine [1].

[1] https://www.vox.com/2015/7/27/9047819/H1N1-pandemic-narcolep...

I know it's CNN (what I could find with 5 mins of Googlefu) and they don't explicitly mention the falsified data part. But the Gamaleya Institute is well known in Russia for falsifying data both as a propaganda machine, as well as to obtain further funding from the federal government. I can't find another source I read earlier concerning a past instance of fraud perpetrated by the institute (it was in German).

So, like nil then? I still can’t find anything beyond dramatized anecdotes to suggest any special danger beyond what is commensurate with the symptoms.

Not the person you're replying to, but looking at similar viruses, there's basically never been a flu-like virus that has no short-term symptoms but serious long-term symptoms, however there have been rushed vaccines that had serious long-term symptoms.

Right now if every activity would be fully available (concerts, conferences, airlines, etc.) every healthcare system across the world would probably be overwhelmed within 2 months, max.

Once we reduce the rates to a trickle, things are probably good enough.

I'm not saying that we shouldn't try to eradicate it, but as with everything, unfortunately, things are frequently taken to a point where they're "good enough" and no further.

The point of a vaccine is that you can't scale it back for populist appeasement; once you have broad immunity you keep broad immunity for long enough that you end up eradicating the virus almost involuntarily. In comparison, a lockdown is much more vulnerable to feel-good measures reducing the effectiveness.

Anything that reduces the R rate sufficiently will mean fewer outbreaks and reduce the strain on the hospital system.

https://www.wral.com/coronavirus/are-nc-s-coronavirus-case-n...

https://www.portugalresident.com/judges-in-portugal-highligh...

(NYT) https://www.nytimes.com/2020/08/29/health/coronavirus-testin...

https://en.yna.co.kr/view/AEN20200429007051320

This is I think why the mRNA vaccines are doing better. They don't use a virus as a vector, they use a less convoluted vector of a more basic mRNA instruction set. They're also in a way more "scalable" in that a future disease or a mutation of Covid with a new spike protein could have a new vaccine made quickly by tweaking the mRNA sequence.

Pfizer and Moderna vaccines are not vectored.

"They're lying to you, they claimed it's 90% effective but actually it's 70%".

70% is still a great effectiveness rate, specially for a cheaper and easier to distribute vaccine.

Why the downvotes? I'm answering the question that is being asked. The study is talking about the side-effects of receiving the vaccine.

> "Also, "There were no hospitalised or severe cases in anyone who received the vaccine".

Can we infer anything from that statement? They seem to be suggesting that the infection might be less serious in the vaccinated population... "

On the other hand we still have no idea how well these vaccines will work. First, we have (as I discussed) two different approaches in the three current candidates, one of which is fairly new and one which is completely novel. We have had only limited time to see how well they work and have only limited experience in broad efficacy, duration of effect, and, crucially, how long they last (it takes a long time to learn if you'll need a 10 year booster!). We don't know how fast the virus mutates away from the vaccine's target (though we do currently think we have a good idea). And we simply haven't tried enough people to get a good handle on side effects.

One of the difficulties in solving these is that new approaches contain unknown unknown. Look at CRISPR-CAS: got a (deserved) Nobel this year yet may already have been discovered to be ineffective or worse in the real world. That takes time to learn.

Now it's not that the people doing the work are idiots -- they know all these problems better than I do. But I am appalled that this is treated by the press as a distinction between, say, a pair of beta implementations of something, one in Python and one in Ruby.

Going back to systems issues: when we don't know these factors we take a calculated risk (really an estimated risk). The social aspects of vaccination (close to ubiquitous use, the risk of any side effects increasing the anti-vaxx rate for other immunizations, which itself could become a public health disaster etc) mean these factors are upmost in public health officials, not whether they have adequate refrigeration.

Vaccines are particularly difficult for reasons like these above -- there's a reason why they have their own special laws and government-assumed liability insurance. I haven't worked on vaccines, so take this as you will, but I have worked in anti-invectives, have designed preclinical and clinical protocols (including first-in-human) which were submitted and approved by the FDA, run clinical trials, have presented to the FDA and defended protocol design, so I have some idea what's involved and how to read the presented endpoints and findings.

https://en.wikipedia.org/wiki/Phage_therapy

Also, all 3 have made various noises about not making a profit etc, it's quite hard to sort out the marketing from what will actually happen at this point. Oxford/Astra have committed to supplying at least 100M doses to low-income countries for under $3 though.

Also, the issue will not be which vaccine is chosen, but above a certain percentage of effectiveness who can even supply enough of their vaccine to meet demand?

I answer your question in a parallel comment; click "parent" on your comment and look at my response to jeromegv

However, I believe that it is different between bacteria and viruses.

From my understanding of the whooping cough studies, they found that some vaccinated baboons who were subsequently infected still had high levels of pertussis bacteria after five weeks. These bacteria couldn't cause widespread infections in the host, but had seemingly found pockets where they were safe from the immune system.

A virus, however, can't find a "safe pocket" away from the immune system in which to survive and multiply. It needs to use the body's own cells and machinery to do so, and (outside of the blood-brain barriers) there aren't cells hidden from the immune system.

You might want to update the comment to avoid confusion.

[0] https://en.wikipedia.org/wiki/Messenger_RNA

[1] https://en.wikipedia.org/wiki/Moderna

I think there was a bit of an implication in the parent post that it would eliminate hospitalizations (instead of just reduce), i still think that is unrealistic.

Simple single stranded viruses like Covid19 are vastly more stable. A good vaccine as long as we force everyone to take it will wipe out covid19.

That would complicate manufacturing, logistics and distribution somewhat right?

There's no reason to expect that the 39 would have a similar age distribution to the population because it's not a random sample.

Your immune system naturally becomes immune after it fights off an infection. But because of the risk of long-term effects and/or death when you're infected with COVID19, people want a safer solution that provides immunity.

A vaccine provides immunity, but at a lesser rate than the actual virus. But 90% (or even 70%) effectiveness is a good thing: it means 90% to 70% people do NOT spread the virus anymore.

You'd think that means 90% or 70% fewer deaths, but that's mistaken. That 70% is compounded over-and-over every generation. If everyone else is vaccinated: you infect 70% fewer people. Those people infect 70% fewer people, and those people infect 70% fewer people.

After 3 generations, a 70% vaccine would wipe out 97.3% of possible infections. And a "generation" in COVID19 terms is roughly 1-week.

---------

So yes, even a 70% vaccine (if everyone took it) is a very, very, very good thing. But the two vaccine trials that finished first were 90% effective, so I think people will prefer the higher-efficacy (at least, if they have access to Dry Ice / -80C storage).

I think you should check your math. Because covid-19 infection fatality rate is "relatively low", only 10 times seasonal influenza (3X for people in their 30's 15X for people in their 70s) the limit where utility turns negative is quite low.

One purpose of approval is to move responsibility from drug companies to the government. They can just pay small fee for National Vaccine Injury Compensation Program or something similar. If you allow volunteers but they have to pay the insurance from free markets, vaccines become too expensive. Drug companies are not willing to give them.

Biopharma leaders unite to stand with science http://www.news.sanofi.us/2020-09-08-Biopharma-leaders-unite...

>The worst vaccine side effect ever is widely considered to be the swine flu vaccine from 60 years ago, where 1 in 100,000 got GBS (a bad disease).

During the 2009 A(H1N1) influenza pandemic Finnish health system used vaccine called Pandemrix, It was almost exactly the same as Focetria used elsewhere in the Europe but it was manufactured using slightly different method. It caused Narcolepsy for 200 kids in Finland and 100 in Sweden before withdrawn.

Thee's another regime that we can all just forget about because it uses the same vaccine but with a different method of delivery that will be discarded in favor of the method proven far more effective. Averaging the two makes no sense.

1. You may end up just getting very short and weak immunity, making this approach ineffective.

2. You may get a combination of immunity which can have different efficiency.

3. For some vaccines of same type this works, but is rarely recommended.

4. Mixing partly mRNA and Adenovirus vaccines doesn't to be winning strategy. It is rather more likely to give another vaccine if after two doses you didn't get immunity.

A caveat here is that different vaccines might use different versions or modifications of the spike protein, in which case it's possible they wouldn't boost each other. This feels unlikely, though, because i think that would also reduce their effectiveness against the real virus.

There are people out there that won't hesitate to kill any number of people for the hard cash or fame, some did it before and that's how the rules were born. I am sure that some of rules could be revisited thanks to the new tech but portraying it as "rules kill people" is intellectually dishonest or naive.

Look what happened with Boeing 737-MAX. Some businessmen, scientists and engineers will cut corners to get their job "done" and every now and then it will be catastrophic.

This does not mean that by not picking your nose you can prevent covid

We would need more data to show that conclusively

Simiarly, we need more data to show that these vaccines are effective and don't have negative long-term effects

a) A virus that is known to cause severe disease in a significant proportion of people, including months-long serious health effects, hospitalisation and death.

b) A virus chosen because it doesn't causing any ill-effects in humans, modified to take on some non-harmful aspects of virus a) and found to not cause any significant harm in tens of thousands of people over several months.

Which is more likely to cause long-term side effects?

Our current testing protocol requires letting the virus rampage through the population before the trials will achieve statistical significance, which is surely more unethical than deliberately exposing a small number of people.

A vaccinated individual will also have milder symptoms.

Together with how rare adverse reactions are to the vaccination, the smallpox vaccine is really a wonder.

Realistically, every major population can be reached in 24 hours by modern transport, and the Pfizer 5000-dose transport package keeps the temperature for 5 days.

The “Spanish flu” is the name of the 1918 outbreak of H1N1. There was also a major H1N1 outbreak in 2009.

If exposing a few people on purpose is a moral wrong, then surely allowing millions of them to contract it by accident so that a few people in your RCT can become infected by chance is a moral abomination.

FWIW, ethicists were split, but mostly on board with HCTs. It was mostly the government that was opposed.

Most of the producers have had their entire capacity bought out in prep for distribution of the vaccine.

This vaccine is cheap, 90% efficient and easy to get people vaccinated. The other ones are expensive, 95% efficient and difficult to get people vaccinated.

Regretfully, it would be not the first example of major economies using the current reality as an excuse/cover to conveniently push political policies/agendas that would otherwise have been impossible to implement (at least not without violating laws/treaties and maybe even basic human rights). I have no intention to fear monger, but I believe way too many are too naive about some of the things that are currently happening. That is, mostly people within those major economies, for people in less fortunate countries already learned the hard way how double-faced those major economies turned out.

How all this will eventually turn out ... anyone's guess is as good as mine. I guess we will all learn, when the immediate emergency of the current situation is over. I would prefer to be/remain optimistic, but thus far there appear to be more reasons for caution and skepticism (at best).

Moderna and Pfizer submitted for approval shortly after they released their initial Phase 3 results. Approval is expected to be expedited, but will not be instant (I've read a few weeks, assuming no problems). Oxford/AstraZeneca will likely follow the same course now that their results are available (they were waiting for enough people in their trials to become infected, same as the other Phase 3 trials).

It is widely expected that large scale distribution of these vaccines will begin in late December.

> Time will no doubt teach us all a lessen.

I doubt it. You need to actually have a position that can be shown to be true or false with the passage of time before you can learn something from the passage of time. You have a bizare, logically disconnected, rant that does not make any predictions. I don't think any course of events would prove you right (or wrong).

> You may want to reevaluate your knowledge about the rest of the world

In context, we were discussing afluent countries, canada europe, etc.

> Also, that vaccine probably won't cost "just" $40 equally for everyone.

They will cost $0 directly. As you say there will be indirect costs based on taxes. However that will be true regardless of if you get the vaccine and be scaled based on your income, so im not sure how you think that applies to your argument sbout class divide.

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.

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.

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.”

"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

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.

> 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.

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".

Wikipedia is not wrong, but you are using their numbers wrong. Your source is talking about the total number paralysis cases that occurred as a result of the vaccine ("250 cases of paralytic illness had occurred"). This includes secondary infections. If you follow the sources listed on Wikipedia page you reference, you will find two sources: my source [1], and [2] (via [3]), both which declare around 60 cases of paralysis in vaccinated persons, and then a larger number (in the order of 200) of total cases. The numbers you reference are referring to only the Cutter polio vaccine, by the way.

And you cannot use the total number of cases in the comparison that you did.

> 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.

If by debase you mean divide, then yes: you would need to divide by more than 200,000.

Your number is {how likely am I to get paralysed by the vaccine polio + how likely am I to cause further paralysis via secondary infection chain}, and you are comparing it to simply {how likely am I to get paralysed by the wild polio}. The first number is inflated a lot by the addition of secondary infections.

The numbers are not at all likely to be similar. As you can see in my (and your) sources, secondary infections accounted for more than double the number of paralysis cases, and therefore there it is likely a lot more people got sick via the secondary infections than the number people who was vaccinated. This causes the big discrepancy between our numbers.

Wild polio causes secondary infections as well, but this is not included in the number you are using for comparison, since it only includes the individual risk.

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

But the lack of error bars means that the calculation is meaningless.

You are assuming that "one in 1000 cases" means exactly one case per 1000 cases, and translate this to 0.100% with three decimals of accuracy.

It is clear from context that "one in 1000" is a rounded number for convenience, and they could very well have runded up from 0.8 or down from 1.4. You simply cannot conclude that the vaccine was 25% worse from your data. But we can conclude that they were in some way similar under your false assumptions, as they both would round to 1.

If you want to conclude anything else except "they are both around 0.1%", you would have to find a source that specifies at least 1 decimal of accuracy in the number incidents per 1000 cases.

Of course, this does not really matter, since you would still be comparing the wrong numbers.

Your argument here is "It's ambiguous and inconclusive when using clearly wrong assumptions that inflate the difference". Taking that argument into consideration, I'm still willing to confidently call it patently false.

Although I agree that I should not have said "Even with your own inflated assumptions it's false that the vaccine was worse than polio." What I meant was "Even your own inflated assumptions does not support that the vaccine was worse than polio", but I clearly worded it badly.

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

I meant it when I used it, and my question had a purpose. If you cannot give any reasonable assumptions where it wouldn't be false (which you haven't been able to do), then it would be patently false to me. The reason it does not seem patently false to you is because you have several misunderstandings in your reasoning and your reading of the sources. But I'm not really interested in discussing this terminology further.

> given that they disagree with the sources I gave

They don't. As I said, you are simply misreading your sources.

But seriously, even if you would manage to find some source which would refute my sources and back up your original claims, I have a bigger point to make now:

During this discussion, you have made numerous mistakes in many posts, beyond my criticism of your faulty reasoning:

(1) Mathematical mistakes

(2) Misreadings of the sources

(3) Inability to clear up ambiguities by looking at the referenced source or secondary sources

Even if by some happenstance you would happen to be right (even a broken clock, etc), you clearly are not confident enough doing this kind of analysis to be lecturing people about the specifics of vaccination risks. You are just as likely to mislead yourself and others as you are to educate.

Of course, this probably won't stop you, since you are not likely to respect my opinion. But hopefully it will still be in the back of your mind next time you approach this topic.

[1] https://www.nejm.org/doi/full/10.1056/NEJMp048180 [2] https://www.cabdirect.org/cabdirect/abstract/19642705083 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928990