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Comment by Throwawayaerlei | Hacker News Reader

Some had faith in the new mRNA technology, while others preferred to rely on more time-tested methods.

Sometimes articles hide a great deal in one seemingly innocuous sentence. From what I've learned from Europeans, there's only one vaccine candidate of that nature the EU considered, a Sanofi Pasteur/GlaxoSmithKline combo, the former providing the infamous spike protein, the latter an adjuvant. Everyone expected this to work like the Novavax version of roughly the same thing that's just reported good U.K. trial results, but Sanofi/GSK's didn't provide a good enough response in the elderly. They were expected to fulfill up to half of the EU's requirements, but they're restarting with a new Phase I trial next month or so, and they might have something ready by the end of 2021.

So if all that is correct, the EU ended up with a very big hole in their plans and not enough redundancy. By comparison only because I'm in the USA and familiar with our efforts, 5 big bets were made with more than a billion dollars each in up front R&D money. Moderna and now Novavax are looking very good, AZ/Oxford and one dose of Johnson and Johnson's is looking OK, with a two dose study in progress for the latter that might show increased efficacy, and only Sanofi/GSK failed in a really major way.

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EU pre-ordered more Pfizer than the US.

Enough for 150 million people in EU, vs enough for 50 million in the US. The US has ordered more after it was approved.

The EU did not pay as much as the US — and signed the contracts much later. Pfizer is doing the rational actor thing and, given a shortage, prioritizing their highest paying clients.

There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company.

The US does currently not allow COVID-19 vaccine exports. Pfizer's plants are only manufacturing for the US while the EU plants are producing for the EU, Isreal, Canada, UK, etc.

coul EU ban vaccine export?

They tried a retaliatory ban against the UK yesterday over the AstraZeneca situation (vaccines in EU plants were exported to the UK last month because the UK were readier to rollout sooner, the UK is not allowing exports from UK plants in return, leaving the EU with a shortfall on vaccines), but because of the way it involved the Northern Ireland border rules agreed in brexit they faced strong opposition from Ireland, also an EU member and I think they've backed down for now

There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company.

But also a multinational, manufacturing their vaccine in the US and Belgium. Initially without any help from Operation Warp Speed, which appears to be a mistake if their December claims about supply chain problems was true, along with eventually signing up to the program and moving up their promise for our second 100 million doses from the 3rd to 2nd quarter.

But that Belgium plant? Something is so wrong with it they're shutting it down for a while to improve capacity ir so they claim. My only good guess is that they have a sterility problem and are finding they have to dump way too many lots they produce after testing for that.

As a Belgian, this is what we've heard and read:

- Pfizer stated on 15 Jan 2021 that they would produce 40% less (60.000 instead of 100.000 doses)

- This delay in production would we compensated in the weeks that follow. In February the production should be compensated.

- This was a temporary measure to scale up production after an extra order was made by the EU

The working group concerning the vaccine and it's distribution was to quote "not amused" by this news and wrote a sternly worded letter.

Source:https://www.vrt.be/vrtnws/nl/2021/01/16/versnelde-inenting-z... Text in Dutch.

Your last point, the additional order, is crucial. And media, Spiegel being one of the most outspoken, created enough pressure tp force that order. Not that overall quantity was an issue, so. But all people saw was shortages. There were no delivery schedules published, so that played a role. But I would have expected some more investigation and research.

Then thr EU ordered more, being under fire, and that let to a temporary shutdown of the plant and even more severe shortages.

Nobody is thinking about that. Instead, the Spiegel is using this to push an agenda against von der Leyen. I'll not defend her, she should never have gotten the presidency (EDIT: become head of the Commission) but what is going on now is just cheap propaganda. And definitely not helping in any way.

Ah yes the good old covid story - sovereign states order some medicine/medical equipment from the companies, and on the airport upon sending it to the country comes US government officials with few extra (freshly printed) suitcases of money to change delivery of that order. Remember quite a few articles from spring about that. 3rd world countries having no chance of receiving what was agreed upon.

I mean I understand, when SHTF its everybody for themselves and fuck the rest. I guess in some twisted view a human nature. But I really have to severely twist it and leave any morals behind the door. Next time somebody will be praising US as some force of good in this world, well they can go fuck themselves too.

/rant

Covid is not nearly as high on the priority list for many third world countries as it is for the US. Here covid shuts down everything. In many African countries it is an order of magnitude less impactful than malaria.

There's less testing, less reporting and much less transparency and awareness. Doesn't mean there's less infection or less dying.

There probably is (less infection) due to the more broad vaccines they receive compared to developed countries, which as a second effect create a little more broad immunity.

Due to the much younger population, most of Africa, India, and Pakistan has had MMR, and it's been found that the mumps vaccine provides significant immunity. In the west most over 35 had measles only, or MR combination without mumps.

DOI: 10.1128/mBio.02628-20

For some reason this hasn't been well covered in the media. I got an MMR booster in June based on preliminary findings, my GP thought I was insane.

Sure but getting 1 million units of anti-malarial drugs properly distributed is an order of magnitude more important than the same quantity of covid vaccines. Just look up their death rates.

> Also, Pfizer is an American company.

BioNtech is a German company. If it would come down to national egotism, BioNtech would just kill the licensing deal and Pfizer wouldn't be allowed to produce anything.

>Pfizer wouldn’t be allowed to produce anything.

Pfizer wouldn’t be allowed to stop producing anything.

I think there are consequences steming out from killing a contractual agreement. They can however license Sanofi and others to produce the vaccine, which is what will be eventually done.

Chinese and the Russian vaccines were not even considered. Now those are used in mass vaccinations, soon EU would be behind all countries but those who barely have any government at all.

People don't even want to talk about that, as if those alternatives don't exists. Non-EU countries in Europe are getting them. Serbia(6.1) and Turkey(2.3) are already close to EU average(2.6) or better on the vaccination process.

The Russian scientists have first discussed Sputnik V with EMA (EU's medicine agency) 5 days ago: https://www.msn.com/en-xl/europe/top-stories/russia-files-sp... ; Hungary, which is part of the EU, has already given the vaccine emergency authorization. However, vaccination in Hungary is lagging behind its neighbors Austria and Romania due low levels of trust (in the Russian vaccine) and general antivaxx sentiment. The Chinese have not discussed their vaccines or filed for marketing authorisation in the EU.

The development, evaluation, approval and monitoring process is described in detail here: https://www.ema.europa.eu/en/human-regulatory/overview/publi...

And on to of that Russia and China are much further behind in the rollout to their own population than the EU itself - see https://ourworldindata.org/grapher/covid-vaccination-doses-p...

It wouldn´t surprise me if Russia and China prioritize to sell the vaccines to other countries than attend their own population.

My parents near Moscow got a shot within a few days after asking for it.

Sure, Moscow. My relatives in Vladivostok report a total collapse of the (local) health system.

Here in Moscow russian citizens can get the vaccine absolutely free in about of 100 authorized medical partners. I've personally got first dose of Sputnik V yesterday without any problems or shortages.

The Russian Gam-COVID-Vac/Sputnik V vaccine looks very good, but for the US or to much of the West, there's a price to be paid for being in an effective state of war with another country. Although Gamaleya is now working with AZ/Oxford to see if substituting one of their doses for one of Oxford's will produce much better results, which I never would have expected.

This is based on the theory that the immune system response to Oxford's virus vector is mostly negating the benefit of the second dose taken 21 days after the first. Gam-COVID-Vac gets around this by using different viruses for each dose, and has 90% efficacy results from their Phase III trial. Unfortunately, no one can yet manufacture it in anything like bulk quantities, but they have set up manufacturing partnerships with a whole bunch of countries from India to South Korea.

The use of Russian and Chinese vaccine is much about trust. No one trusts that the Russians have done proper trials or that the reported data is accurate and no outside party has a means to verify their claims. Time will tell - I very much hope it works, but wouldn't be surprised if it didn't.

France allowed the Pasteur institute to fail - a much desired vaccine was stopped because it wasn't effective enough. Impossible to imagine the same happening in Russia, as Putin needs to project power.

> the theory that the immune system response to Oxford's virus vector is mostly negating the benefit of the second dose taken 21 days after the first

Do you know if there are more trials underway to verify this? I'm guessing it ties in to AZ's encouragement for delaying the second dose i.e. wait until the immune response has died down. I think UK medical consensus is currently recommending 12 weeks rather than the original 3-4.

Non-sequitur, but true: this is a political hatchet job from delivered by a center-left newspaper to a center-right politician. The key to this crisis and article can be found in the middle of the article: "...von der Leyen's press department has been energetic in its defense of the Commissions actions. After all, the EU has secured rights to 2.3 billion doses of vaccine, they have pointed out, with 760 million of them from BioNTech/Pfizer and Moderna.

But what use is that when the availability of the vaccine will remain so limited for the foreseeable future? When the producers are unable to deliver what they have agreed to – or can only deliver much later?"

Von der Leyen deserves all the hatchet jobs she can get... She is the child of a political dynasty and hasn't done anything well for citizens in her life.

As a French I'm still extremely bitter about the insane manoeuvering by the EPP to put her in place. Then again, finding anyone even remotely competent in the EPP is probably quite hard.

Besides her parentage, you forgot to mention that she's a German woman and mother in a position of power, to fully "justify" your ad hominem attack.

It's not an ad hominem when you're talking about someone's competence. Has she done anything good or not?

It's not a hatchet job. The EU's handling of the vaccine has turned into an incredible disaster. Given the stakes, and the magnitude of the disaster, it's only natural the architect of that disaster get evaluated critically.

It is both. And especially the Spiegel has an issue with her. Also has a history of pushing agendas.

Personally, I blame part of the availability issues, caused by the Pfizer plant "shutdown" in Belgium, on that hatchet job. The Spiegel was among the first to use the unsatisfactory vaccine availability against von der Leyen. Fair enough, but as solution they called for increased ordering. Pressure built, frustration kicked in and then every news outlet demanded the same thing. Local politicians supported that narrative, they avoided discussions about their own fuck ups. Then the EU ordered more, demand exceeded capacity, and Pfizer reworks its plant. That resulted in even worse short term availability issues. So great job, I guess.

The 12 weeks is not about maximizing protection for an individual recipient, but was a decision made solely to get the first dose to more people faster.

In terms of effect on effectiveness per person it is purely speculative.

That's not correct for the AZ vaccine, the longer interval is supported by the trial data, and we simply lack that data for other vaccines, though for most other vaccines historically a longer interval than 3 weeks is better for a second dose.

Exploratory analyses showed that increased immunogenicity was associated with a longer dose interval (see Immunogenicity Table 3). Efficacy is currently demonstrated with more certainty for dose intervals from 8 to 12 weeks. Data for intervals longer than 12 weeks are limited.

https://www.gov.uk/government/publications/regulatory-approv...

If the AZ vaccine actually better with longer delays, that's great, but it does not change the fact that the political decision to increase the interval was made at a point where the UK was starting to give second jabs of the Pfizer vaccine, and second round vaccinations with the Pfizer vaccine were cancelled for a lot of people as a result, prompting Pfizer to warn they didn't have data on what that would do.

As such the decision was very clearly made on the basis of getting more people some protection, whether or not they could be confident of the effect of the long term protection across the various vaccines.0

It's a reasonable gamble to take given the amount of spread, and is not a criticism (though the way the change was communicated was absolutely awful), but if it had been a decision taken based on available data one would expect the schedules actually tested by the manufacturers to be adhered to, even if different between the vaccine.

> Chinese and the Russian vaccines were not even considered.

The Russian vaccine's "trial" was mostly a non-consensual trial carried out on their military. I expect this lowered confidence.

Does China have a vaccine with decent effectiveness yet? Last time I read about it, the number was around 50%.

Turkey says China's Sinovac COVID vaccine 91.25% effective in late trials

https://www.google.dk/amp/s/mobile.reuters.com/article/amp/i...

I don't see how being consensual or not has any bearing on its efficacy. Not to mention that any model I have of russian military (or any military) tells me that finding volunteers for a pandemic-ending vaccine would be a very easy task.

> being consensual or not has any bearing on its efficacy

Not on efficacy, but in reported efficacy. Basically: if you're willing to be unethical about testing X, why would we trust you to be ethical when reporting about X.

That's the opposite of the halo effect. They're bad guys, so everything about them is bad.

You can say that results are unreliable because they're not open about the details, or didn't provide enough data, or the data they provided doesn't make sense. Vaccinations being consensual or not is unrelated to the topic.

> Non-EU countries in Europe are getting them.

At least one EU country will soon be getting them. Hungary has approved [1] and also ordered [2] the Russian vaccine. Hungary has also approved [3] but not yet ordered the Chinese vaccine.

[1] https://www.dw.com/en/covid-hungary-fast-tracks-russian-vacc...

[2] https://www.aljazeera.com/news/2021/1/22/hungary-buys-russia...

[3] https://www.reuters.com/article/us-health-coronavirus-vaccin...

I wonder if the Chinese vaccine with 50% efficiency could be used for herd immunity at all. Im not a virologyst, but the false safety of most people vaccinated with it in a country might could trigger even more death? The Chinese vaccine is not even tested above 59 years old. If the young is vaccinated and start to party etc the new more infectious variants could still spread and can reach even more elderly.

Sure it can. Vaccines are only one part of the puzzle. With 50% population immunity you need far (far) less natural immunity to reach an R number less than one, at which point outbreaks don't grow anymore.

Obviously these magical mRNA vaccines with their 95% numbers are going to be more effective. But that's just a (very) happy scientific accident that they worked out. Historically vaccines haven't been anywhere near that effective and have still controlled disease. Hell, the flu shots we get are like 30% effective and they still save lives every year.

The problem is one of public confidence. 50% effectiveness would be very useful epidemiologically, but you'd still get a lot of pissed off infected people who thought they were safe. Conveying the message that we're going to stick a needle in your arm and it might not do you any good to a public that's already rife with scepticism about vaccines is a PR problem I'm very glad isn't mine to deal with.

AFAIK there's two Chinese vaccines with published data: Sinovac and Sinopharm. Sinovac hasn't had great results but Sinophram has shown initial effectiveness numbers similar to AstraZeneca.

It should be noted that this is likely nit worse than Pfizer, despite marketing. The 50% for Sinovac is real world data; the 95% for Pfizer comes from company phase 3 data.

Well, last night a reputable Israeli HMO posted it’s real world data for Pfizer, and it’s 50% after 18 days and doesnt seem to get much better (but they don’t have enough data yet to know for sure).

And now, although everyone claims Pfizer says you get 50% after 1st dose and 95# after second, if you read the actual filing, that’s not what it says; efficiency is achieved at day 13 by Pfizer data almost fully; and the reduction in severe disease (the only interesting endpoint) is 75% with confidence interval 0-100%

"The data, which looked at more than 700,000 fully vaccinated people in Israel, found that only .04 percent of people contracted Covid-19, according to the head of Israel’s Ministry of Health, Dr. Sharon Alroy Preis at a press conference on Thursday.

The type of vaccine Israel has mostly used is the Pfizer/BioNTech vaccine with a small number of doses from Moderna. The two vaccines use the same technology, and in clinical trials were found to be about 95% effective. " https://edition.cnn.com/world/live-news/coronavirus-pandemic... Can you share your datasource claiming that efficacy is only 50%?

https://www.medrxiv.org/content/10.1101/2021.01.27.21250612v...

You’ll have to actually read it, or find a tldr from someone who knows what they are doing.

The same calc that leads to 0.04% above would say overall covid mortality is 0.08% and is intentionally misleading - but no news media so far (in Israel or outside) has done any review. They are all parroting the misleading numbers.

Anything but primary data these days is suspect. (Pfizer’s own primary data, btw, says severe disease is 75% RRR with CI 0-100%. Did you see anyone reporting on that?)

Edit: to add: Israel is an a horrible bind right now. The vaccine is only 50% effective but gov has done very badly in handling the disease and promoted the vaccine as “our way out”, so the gov is attempting to hide that data. Unfortunately for them, Israel is too small and the culture not supportive of hiding this, even if at this point the mass media is cooperating with the government.

Quoting from the link you provided:

"We demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection."

I.e. if you take only the first dose of the two required then 13 days after taking it you already get an effectiveness of 50%. Therefore they recommend that people take the 2nd dose as prescribed. They don't mention effectiveness one week after the 2nd shot, which is what Israel considers to be immune (i.e. "green passport" status).

The 95% everyone quotes is for mild disease.

For severe disease, Pfizer had 4 in the control group, and 1 in the vaccine group. That’s 75% RRR, with a confidence interval that spans 0-100%.

Look at the graphs here and in Pfizer’s. Immunity seems to taper at 12-18 days and stay there. The 2nd vaccine does not seem to confer more immunity - just expected to last longer time. This article looks at more severe disease than Pfizer’s 95% endloint (though possibly not severe as their “severe disease” endpoint - I don’t remember what definition each uses, but just in Israel the “severe” definition has changed several times)

Please stop spreading lies. The paper is only about "The effectiveness of the first dose of BNT162 ..."

50% efficacy after the first dose is exactly the number that BioNTech reported in its Phase3 trial. So nothing unusual here. That is why the 2nd booster shot is needed to get to 95%.

No it is not. Have you actually read either Pfizer’s report or this paper? Looked at their data?

The graphs, both in Pfizer’s original report and in this paper, show that past about two weeks, there is almost no change. Please look at the Pfizer graphs and tell me where the great advance is from 50% to 90%

Also, if yo actually read the Pfizer report, you’ll notice the 95% is for mild disease - a totally uninteresting result. For severe disease, it is 75% with a CI spanning the whole 0-100% range.

Well, the solution to this dispute is easy => We just wait another 8 weeks:

(1) If am right, then Covid is gone in Israel by end of March.

(2) If you are right, Covid will be still a huge problem in in Israel.

I won't hold you to this, even though you are guaranteed to lose in this bet even if you are right - because the trial for 5-12 that would allow to vaccinate them is not expected to yield any data until later than that. Even if you are right, it will still be here in that age group.

Also, there's a nature paper from last week that shows incredible correlation between Sun UVB at 34% of equator and the date that a wave starts. Covid will be gone by June, just like last year, thanks entirely to that effect (and possibly arrive again in Sep/Oct, or not). I'm not interested in meterology, but it's possible that even if I'm right, by end of March covid will be very dim in correlation with UVB exposure.

The amount of data actually attributable to cause and effect is incredibly miniscule. I do data science for a living. The headlines are basically all wrong, most discussions are, and quite a bit of the primary data cannot be right.

added: p.s - Did you actually read the papers before calling me a lier (or after?) or just did it based on headlines. I'm not holding it against you either way, just wondering.

>Well, last night a reputable Israeli HMO posted it’s real world data for Pfizer, and it’s 50% after 18 days and doesnt seem to get much better

Their initial results are actually very encouraging[0] in this regard.

[0] https://www.ynetnews.com/health_science/article/Hk2URcnku

That is propaganda. The real data is in https://www.medrxiv.org/content/10.1101/2021.01.27.21250612v... and is 50% (not uniformly over age groups, but 50% is a good summary of it all).

The Israeli government failed miserably in dealing with covid. They were successful in getting the vaccines (and thanks to the HMOs and no thanks to the government, deploy them quickly) and selling the hopium that this will solve everything and make up for the failure so far.

So now they are in a very bad place. If they admit the real stats publicly before the vaccine project is done, people will stop getting vaccinated (not because 50% effective is bad - but because they’ve been misled). No one wants that. I suspect that’s why the media (ynetnews - a local USA Today equivalent, included) are all parroting the official statements without review comment or criticism.

The numbers in the ynetnews are not false but they are (likely intentionally) misleading. If you used the same arguments, you’d get an IFR that’s way lower than the flu, for example. They cherry picked a completely meaningless statistic that looks good, and claimed it is the vaccine efficiency. It is not.

There seems to be a major flaw in comparing the data between the two studies: the Pfizer paper is counting Covid19 cases (symptomatic cases with confirmed PCR for SARS-CoV-2), while the Maccabi paper seems to be counting SARS-CoV-2 infections overall, which would include asymptomatic cases.

They even say so explicitly:

> Second, our case definition was positive SARS-CoV-2 PCR test irrespective to presenting symptoms that defined COVID-19 cases in the RCT. This might explain the discrepancy in results.

So, this new research is not really contradicting the Pfizer paper in any way - they are simply measuring different quantities.

Still, it's nice to know that the vaccine also offers protection from infection, not just the disease.

You're mixing up two different datasets. The former deals with first dose effectiveness (which we've always known to be lower - that's why the regiment is two doses), the latter with the full two dose regiment.

Ynet is Yediot, which is either the biggest daily newspaper or the second-biggest depending on how you count, either way it has more influence than Yisrael-Hayom. They do neglect their English site, but this particular content matches their Hebrew publication. It can't be seriously compared to USA Today (which is one of those magazine you mainly get for free, and barely has any dedicated readership).

Please look at the graphs and data, not the headlines.

Nothing magical happens past day 12 from the first vaccine in the Pfizer paper, or day 18 in this paper. Seriously. Look at it.

Yes, ynetnews is ynet/yediot. Their reporting of covid is exactly parroting the government with no criticism whatsoever so far.

I’m not antivax, I’m provad. 50% is pretty damn good for a first attempt. But everything has become so political, I go read primary data - and it is NOT remotely close to what the headlines say.

Edit: looking at the graph [1] more closely, I understand what you meant - there is no visible change in the slope past day 12 after dose 1 (dose 2 was administered on day 21). So the patient data actually shows that the vaccine achieved its maximum efficacy ~12 days after the 1st dose, not necessarily related to the 2nd dose at all.

Original comment:

I don't know where you're getting this, but the Pfizer paper [0] clearly shows that disease prevalence is much lower after the second dose:

> Among participants with and those without evidence of prior SARS CoV-2 infection, 9 cases of Covid-19 at least 7 days after the second dose were observed among vaccine recipients and 169 among placebo recipients, corresponding to 94.6% vaccine efficacy (95% CI, 89.9 to 97.3).

> Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a vaccine efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the vaccine, starting as soon as 12 days after the first dose.

You are right about the severe cases though - they had 1 in the vaccine group and 4 in the placebo group, which is far too little data to draw any meaningful conclusions from (it's also worth noting that the single severe case in the vaccinated group occurred >7 days after the second dose, so there is absolutely no data to draw conclusions on severe disease impact with a single dose).

[0] https://www.nejm.org/doi/full/10.1056/NEJMoa2034577 [1] https://www.nejm.org/na101/home/literatum/publisher/mms/jour...

Indeed that is what I meant. Thanks for trying to understand even if I wasn't perfectly clear in my wording.

Indeed, maximum efficiency is achieved after 12 days in Pfizer data (and similarly in the Israeli data). That's the reason some countries consider giving just one - they suspect it won't be as-long-lasting without the booster, but that's from prior experience, not anything specific for this vaccine.

I'm incredibly frustrated at the amount of people parroting "yes, two weeks after the first vaccine it's 50%, two weeks after the 2nd it's 95%". Yes, that's what Pfizer said, and I think I managed to reproduce their calculation - and if I did, it is intentionally misleading.

It seems a lot of people are religiously believing the headlines without looking at the publicly available data. I thank you for looking at it.

I'm not referring to the Pfizer research, I'm referring to the Maccabi paper. The data is explicitly for the first dose and not the second. The paper also mentions the effect starts from day 18, not beforehand - maybe you should read it again.

What Maccabi did publish on the second dose, it was in a much more encouraging note. Granted, not a peer reviewed paper, that would be difficult given lack of time.

Claiming Yediot is parroting the government is delusional. I won't belabor about it, since most HN readers deserve better than Israeli politics or the eternal elections.

The main point that beagle3 makes is that the Pfizer study actually shows ~89% efficacy starting 12 days after the first dose, which improves to ~90% immediately after the 2nd dose (day 21) and ~95% 7 days later (day 28).

The Maccabi study was designed with this comparison in mind: they look at efficacy in days 1-12 and 13-24 after the first dose. They are mainly interested in comparing the Pfizer results for days 13-21 (89% efficacy) with real-world data. They show that the real world data is actually showing only ~50% protection in days 13-21, compared to 89% in the Pfizer data for the same period. This is somewhat disheartening.

HOWEVER, the Maccabi paper is not measuring the same thing as the Pfizer study. The Pfizer study only looked at symptomatic infections (Covid19 symptoms + positive PCR for SARS-CoV-2), while the Maccabi paper is also including asymptomatic infections.

Neither study includes sufficient data to accurately compare with the other one - the Pfizer study did not do PCR tests on anyone who didn't show symptoms, so we don't know how many asymptomatic infections they had exra; and the Maccabi study didn't record symptom information, so we don't know what percentage of those infected were symptomatic.

All of these numbers and facts are explicitly mentioned in the Maccabi study, it's not me reading into the data on my own.

You are correct, but this doesn't show a conspiracy like a certain other commenter hints at.

We always knew that the the Pfizer vaccine has a lower chance of preventing transmissions, the original treatment regime was two doses, and we further know that the Pfizer vaccine wasn't originally tested vs B117 and the other mutations and it's quite possible it has lower efficiency vs those.

Still, there's a good chance two doses offer even higher protection, and frankly if all adult population receives only the 'symptomatic' protection the plague will be over as far as Israel is concerned (barring yearly(?) boosters) - hearing there's any protection for asymptomatic infections is heartening.

No, it doesn’t show a conspiracy.

The political rather than medical decision making in Israel is out in the open, there’s no need for conspiracies.

It took @RanBalicer 3 days to acknowledge the abysmal data, and it was not “gee, we might have made a mistake in the model”, it’s always “an unexpected twist in the mutation/behaviour/population”. It is beyond embarrassing. But I digress.

Let’s just agree that the 95% RRR for “reported mild symptoms” is meaningless, and that the 50% number from Maccabi is actually good news, and we should use that number in models and predictions?

I don't have an anti for Balicer, so I don't care if his models are right-or-wrong. It's natural to have mistakes, and changing position after 'only' 3 days is fine enough. I also agree that we heard some good news, but I do think that the 95% RRR is relevant - people who have a strong enough immune reaction to make the disease asymptomatic are people who have been protected. Once enough people have been protected, than hospital burden will go down and Israel could manage this thing.

The 2nd dose data maccabi sent out is pure PR; It's basically "We finished vaccinating yesterday, and almost no one got sick yet!" which, while true, is the most fudgible statistic ever. I'm ignoring it and waiting for the 2nd paper from Maccabi and the 2nd release from the K(alkstein) Institute - whom I trust more than even the Maccabi medarxiv paper (and I do trust them, about a billion times more than government press releases and the incredibly compliant mass media).

Please stop spreading lies. The paper is only about "The effectiveness of the first dose of BNT162 ..."

50% efficacy after the first dose is exactly the number that BioNTech reported in its Phase3 trial. So nothing unusual here. That is why the 2nd booster shot is needed to get to 95%.

See my other reply to the other copy of your comment.

Please prove that you actually read the Pfizer report and not just repeating headlines before calling me a lier.

I might have misread some data, but I see no indication that you are in a position to judge that.

Also note that even if the vaccine couldn’t prevent one from getting infected, it could still reduce the severity of the infection (thus saves lives). I’m _guessing_ a less severe infection could potentially reduce the rate of infection as well?

> virologyst

Is this an actual spelling in some dialect of English?

It looks interesting. In medicine, when I see “gy” I’m thinking gynolocologist.

Google Search Trends reports only tiny quantities of “virologyst” compared to “virologist”, and all from countries which are not English-native, so I’d classify it as a spelling mistake.

I still don't know whether my parents should get the Chinese / Russian vaccines or not.

I'm more concerned about lack of efficiency than safety. The problem is that after they get one of the vaccines, they won't have any chance to get more from the Pfeizer vaccine when it arrives.

The Sinovac CoronaVac efficacy is not useless, but not very good from what I've read. Gam-COVID-Vac on the other hand is around 91% https://sputnikvaccine.com/newsroom/pressreleases/the-sputni..., which is quite good while not reaching Pfizer/BioNTech's 95% (the German firm BioNTech developed the vaccine, they partnered with Pfizer to test, manufacture, and distribute it).

Ah, I forgot an important detail: my parents are over 70 years old. The biggest problems with these vaccines are that they can be less effective in old people, and it’s hard to find data on old people.

Just as an example Sinovac is not even used in old people in China as far as I know.

There’s a similar question with AstraZeneca right now, German vaccination committee would like to see more Phase 3 data on old people before moving into Phase 4.

This gets complicated, live virus and mRNA type vaccines that hijack a small number of your cells for a full immune system response aren't as far as I know normally used for people that age, see https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html and note "zoster live" has been removed from the US market.

On the other hand, they might just wring out the best response possible at a slightly greater risk. Here I'm assuming your parents shouldn't try a PRC vaccine, so it's virus vector Russian or mMRA Pfizer, both essentially accomplishing the same thing, both with high overall efficacy.

Or look at it this way: if they don't get a good result from either of these two vaccines, they're not likely to fair well from a real infection. Maybe. We really don't known why even at their age most people survive.

The other factor is how much you trust quality control. Pfizer > Russia >> PRC in my book, but I have absolutely no read on Russian quality. But also note Pfizer/BioNTech is useless if not properly handled to its strict temp and physical requirements.

You do know that the error bars on 91% and 94% could make the inverse outcome or equality as likely as your belief in the 94%-is-better..

Not to mention, the 95% is on the relatively uninteresting “mild disease” endpoint. Israeli data came out in the last 24h on severe disease - and it’s only 50% RRR

> EU would be behind all countries but those who barely have any government at all.

Ouch. Reading this from Canada hurts.

(We are way behind EU and I would be very surprised if we get ahead of them at any point).

Uh, why do you think that?

You don't appear to be behind the EU in any substantial way. (2.61 doses/100 administered for EU, 2.49/100 for Canada)

https://www.bloomberg.com/graphics/covid-vaccine-tracker-glo...

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You've purchased more vaccine relative to population than basically anyone else in the world and you appear to be higher than the EU in terms of the line for deliveries.

https://www.bloomberg.com/graphics/covid-vaccine-tracker-glo...

> Uh, why do you think that?

It has been an unfolding story for the past couple of weeks. I wish I know of an article which summarized everything with a timeline, but I do not. The gist of it is that, Canada has purchased many vaccines, but they will not be coming soon enough. It also lacks the leverage that US, UK, and EU have in terms of the production being domestic. So when Pfizer ran into production issues, initially they planned to cut Canada's deliveries by ~50% for 4 weeks but EU's by a 8% for 2 weeks. Of course the issue has developed since then, but the central issue remains the same: Canada is not a priority for getting vaccines, and does not have the leverage to make itself the priority. I am deeply concerned that EU would simply block exports to Canada to make up for the shortfalls in its share of the vaccines. Even before the new laws, that was close to what was happening in practice, with deliveries to Canada being affected most and to EU the least.

Also, Canada's not being far behind is because we started earlier. We have seen our vaccine doses administered per capita ranking go from 6th to 21st. Most of the countries that got ahead of us are the EU countries. And every day, we fall behind more and more EU countries, as our deliveries have been deprioritized compared to EU's. Or at least so it seems. We won't know the full truth until the dust settles. Probably a year from now.

> initially they planned to cut Canada's deliveries by ~50% for 4 weeks but EU's by a 8% for 2 weeks.

This is simply because of different contractual obligations to the different parties. If I owe you $100 by the end of year, but owe someone else $20 by end of month, I'm going to give full priority to repaying the other person.

> I am deeply concerned that EU would simply block exports to Canada to make up for the shortfalls in its share of the vaccines.

Unwarranted: they've explicitly said they won't. Lots of articles on your news source of choice. one random example: https://www.nationalobserver.com/2021/01/28/news/eu-health-o...

As a fellow Canadian, it simply doesn't seem to be a big deal yet. May become one, but whatever.

> This is simply because of different contractual obligations to the different parties

I am not so sure. Canada was the 4th country to sign a contract with Pfizer. We were ahead of the EU. The initial statements by the Canadian government about the reduction in Pfizer production capacity was that they expect all countries will be affected similarly, but the next day we learned that Canada will be affected an order of magnitude more that Europe. It's unlikely that the government did not know what their contract said when they made those statements. In retrospect, Pfizer probably calculated that pissing off Canada is preferable to pissing off Europe and acted accordingly. Now we see that Canada accepted the slowdown gracefully, but Europe threw its weight and started changing the rules. Politically, they made the most expedient decision. But it was and is unfair to Canada.

Pfizer has been pretty explicit with their comments that the deliveries will still meet the amount required by the end of quarter. Perhaps the EU has end-of-month targets instead.

I'm just not that concerned about it personally. There'll be a political price to pay if it doesn't work out, as well as a contract violation price for the manufacturers. I don't expect I'll be able to get a vaccine until August at the earliest anyway.

I wish addressing climate change was covered with the same urgency by media (mainstream, niche, social, all of the above)

Canada has no large scale vaccine production capacity so even if they could license the production they couldn't produce any decent amount any time soon.

I hope this is something that changes post pandemic.

I just hope there is a post-pandemic era. Too many unknowns still about the mutations and whether they’ll out-maneuver the vaccines.

Lots of reason for optimism. The vaccines can be retargeted, and like the flu vaccine, approved with a faster trial. And the mRNA vaccine production can continue to scale up.

So if there is a need for a new vaccine, we can likely deploy it with a shorter interval to availability and much larger initial volume.

We can also become more disciplined. We don't need to go all the way to a strictly enforced lock down to improve on the social distancing that we've done the last year (at least, not in the US). And we can try to get people to more widely accept contact tracing/tracking.

Right, but for the most part your optimism is about better managing an ongoing pandemic, which is certainly not what most are hoping for.

Get the active infections down and roll out a (well targeted) vaccine quickly and you end a pandemic.

I'm saying there's reason to be optimistic that we will be able to respond successfully even if the current vaccines don't end the pandemic (and it likely would be reasonably quick too, our tools are much better now than 12 months ago).

At some level of production capacity, convincing people in high risk areas to social distance and convincing people to get another vaccination are the hard parts.

We are in the post-pandemic era of HCoV-OC43 despite not having a vaccine. It is very similar to SARS-CoV-2 and there is circumstantial evidence that it caused the pandemic of 1889. The only reason it kills few people today is that most of us are infected as youths and build up immunity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252012/

I wonder why not cover younger people with the GSK version and older people with some other vaccine?

Excellent question. Probably the biggest factor is that Phase III trials are insanely expensive, like a billion dollars plus or minus. High touch, 30,000 people minimum for the US, lasts two years, etc. Sanofi/GSK is hazarding some of their own money in this, and has to look at the market for COVID-19 vaccines, which is obviously weighted towards the elderly.

Might also be risk management in wondering if the final results for the younger would be disappointing or worse, this problem with the elderly was learned through surrogate endpoints from serological as in blood testing of immune system responses. See Oxford for how they were led astray from their first big 500 Phase I/II people test of their vaccine platform, and achieved much worse results than they anticipated when put in the crucible of multiple Phase III trials and the real endpoints of getting COVID-19, or serious cases of it.

> Phase III trials are insanely expensive, like a billion dollars plus or minus

Do you have a source for that?

JAMA Internal Medicine says a median of 19 million, but that's for all drugs, not specifically vaccines.

https://jamanetwork.com/journals/jamainternalmedicine/articl...

Not a good or recent one, but reading the linked article indicates the sort of trials being done for vaccines will have a median much greater than the $19 million you cite. These trials enroll 30,000 subjects at minimum, and take 2 years, both of which substantially exceed the maximums cited in the paper that they or anyone else they knew of had tried. In the case of length, by 4 times.

Thinking further, a billion is too high an estimate today, because these trials or one I looked closely at use smartphone "ediaries" to reduce the number of direct person to person contacts. But they're still high touch affairs, nothing substitutes for phone calls and direct examinations, although the latter are limited in number, but start with a general medical exam.

Thanks for bringing that paper to my attention, I'll look more closely at it later.

That figure doesn’t pass the smell test. I think you’re confusing the cost of a phase III trial with the total end-to-end cost of developing new drugs.

Injecting 30,000 people twice with a vaccine & tracking their post injection experience does not cost $1billion. (Googles) The FDA thinks a phase III trial costs about $20million. So there you go.

Gentlemen, the hole is due to the fact that no company has the large scale productive capacity for the newly discovered COVID-19 vaccine.

Ordering earlier and paying more would just have shifted distribution around, and would not have made more doses available. Every vaccination done in the US or the UK means one less vaccine dose for Europe.

And that is not "ducking responsibility", it is basic logic - as one cannot fit 10 pegs in 9 holes, one cannot vaccinate 10 people with 9 doses.

Your model seems to assume a fixed production capacity? It would seem plausible that if you paid an extra billion or two, companies could find a way to scale up production faster.

Well the fact that the companies own the stuff that was researched with tax payer money, which then tax payer money must buy again also doesn't help to scale. As there is no real market but just an oligopol of producers. If the formulas would be public domain, the producers can compete who is fastest and there would be much more and they still earn good money...

I just have been sollicitated to test the Janssen/Johnson and Johnson. Seems that it is still in Phase III in Western Europe. I'm not 100% sure to want to participate, split between: ok there is enough vaccine i'll be vaccinated in 3m OR OK i need to do this because we need more vaccines.

Janssen has finished recruiting for their 1 dose Phase III trial, but is still doing that for their 2 doses 8 weeks apart trials, this huge one https://clinicaltrials.gov/ct2/show/NCT04614948 and this small one in the US and Belgium https://clinicaltrials.gov/ct2/show/NCT04436276 There reporting on their one dose trial's efficacy results is pretty good, about what I expected, so if this gets you that one first dose ASAP its seriously worth considering. It's also a relatively mature platform, used previously for their Ebola vaccine which passed an European Phase III trial, but wasn't the earlier one that made such a difference in the last outbreak.

The other vaccines you might get are less mature platforms, AZ/Oxford 2 doses 21 days apart has less efficacy than Janssen's 1 dose (Oxford had not before 2020 ever tried testing their platform on more than 40 people at a time), the mRNA vaccines I'm sure you've heard all about, but I wouldn't make any bets on when Pfizer will be able to provide you a dose from their currently? closed Belgium plant.

You're saying this despite the weekly pcr and different efficacy testing methods?

Can you be more specific? I'm happy to drill down to the individual Phase III trial protocols, but want to know which ones you're referring to. Plus I'm pretty sure I left myself a lot of wiggle room with efficacy claims like "very good" and "OK."

Some of the efficacy methods involved you saying you're sick and then getting tested (Pf/Mod). Others were you were swabbed weekly (thereby catching asymptomatic infections (AZ)). So the efficacy rates between the bunch aren't apples to apples comparisons. AZ has an understated efficacy rate, so it's better than 'OK'.

It explains Jansens efficacy being broken down up to the number of hospitalisations (where it reduces nearly all of them)

AZ has an understated efficacy rate, so it's better than 'OK'.

Maybe, but their and Oxford's testing has been such a mess, with more than one lie promulgated by AZ in public claims (the blended efficacy based on an appalling Oxford mistake that suggested a better dosing that later didn't pan out), that I don't have much confidence in their current Phase III claims. Which date back to early December and haven't been publicly updated. Those are based on 4 trials in different countries, less than 6,000 each for the official 21 day apart dosing and a 70% efficacy claim.

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