Pfizer and Biontech provide update on Omicron variant | Hacker News Reader

Pfizer and Biontech provide update on Omicron variant

pfizer.com

342 pointsamichail639 comments

This is the scientific meat of the press release where it claims a 25 times neutralizing antibody titers against the Omicron strain with a third dose of Pfizer-BionTech:

The sera were collected from subjects 3 weeks after receiving the second dose or one month after receiving the third dose of the Pfizer-BioNTech COVID-19 vaccine. Each serum was tested simultaneously for its neutralizing antibody titer against the wild-type SARS-Cov-2 spike protein, and the Omicron spike variant. The third dose significantly increased the neutralizing antibody titers against the Omicron strain spike by 25-fold. Neutralization against the Omicron variant after three doses of the Pfizer-BioNTech COVID-19 vaccine was comparable to the neutralization against the wild-type strain observed in sera from individuals who received two doses of the companies’ COVID-19 vaccine: The geometric mean titer (GMT) of neutralizing antibody against the Omicron variant measured in the samples was 154 (after three doses), compared to 398 against the Delta variant (after three doses) and 155 against the ancestral strain (after two doses). Data on the persistence of neutralizing titers over time after a booster dose of BNT162b2 against the Omicron variant will be collected.

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At the bottom of the press release it mentions that Pfizer is the marketing distribution partner for BionTech in many countries. Does anyone have a list where BionTech distributes directly?

"BioNTech is the Marketing Authorization Holder in the United States, the European Union, the United Kingdom, Canada and other countries and the holder of emergency use authorizations or equivalents in the United States (jointly with Pfizer) and other countries."

IIRC Biontech distributes directly in some part of Europe that includes Turkey but I wouldn't bet on Kazakhstan and its neighbours. (Also, Pfizer does more than distribute, it also produces the stuff somewhere in the US, and contract manufacturers including Rentschler Biopharma produce for both of them.)

Mongolia got doses from Covax that are labeled with Pfizer. On the certificate it is labeled with both names.

It's interesting, this differs from recent results suggesting that boosting with vaccines derived from the original Wuhan variant is relatively less effective against newer variants like delta: https://www.medrxiv.org/content/10.1101/2021.08.12.21261952v....

Well the problem suggested by other research is that when vaccinated people are infected with a functionally different strain they don’t appear to create new antibodies.

This is consistent with other research showing that people who are vaccinated then infected are more likely to get reinfected than those who were simply infected and recovered. The alternative outlook here is that vaccinated people are more likely to be at risk populations with immune systems that don’t function as well (immune compromised/elderly)

This has always been my fear. I'm vaccinated (Moderna) and got COVID in September. I recovered quickly - about 3 days. But I'm worried that my body did not get to have a proper immune response and that as such, I'll have to continue get vaccinated forever whereas if I had just gotten COVID without the vaccine maybe I would be set. But I haven't found _much_ data to back up this concern.

That's the usual way it goes, as long as relatively high mortality virus is circulating in most of the world population.

Both infection- and vaccination-produced immunity decays over time. So everyone's choice is between keeping up their vaccination, or getting COVID repeatedly.

Which boils down to a question of whether you think being vaccinated or getting COVID is less risky.

Yes, there's some +/- on the decay rate, but in a relative weighting between risk (COVID without immune system primed) and needing more frequent boosters, why pick the COVID option and roll the dice on death or permanent organ damage?

Personal choice, I stay vaccinated, at least until (fingers crossed) the circulating strains of COVID evolve to be less dangerous.

“Relatively high mortality”? Can you think of any virus even close to COVID mortality that we take these kinds of draconian measures to prevent?

Can you think of any virus that caused hospitals around the world to be overwhelmed with patients, compromising their ability to treat normal ailments?

Hospitals are frequently overwhelmed and operate at capacity limits basically constantly in large parts of the world

Yeah let's play this game! Let me count all the viruses that killed close to a million Americans in the last 2 years!

1. COVID

Transmissivity /= mortality rate

Why are we talking about the mortality rate and not the overall mortality of the virus? Seems that the metric that matters is how many people it kills. Especially since we are actively fighting the virus harder than most in the past few years.

I'm sure you know this but there hasn't been a pandemic virus as virulent and deadly as COVID-19 in modern times.

For some perspective, Chicken Pox killed roughly 100 Americans every year and that vaccine was mandated in effectively all schools and universities across the country.

The chicken pox vaccine was invented in Japan in the 1970s, was approved for kids in the US in 1995, and required in schools sometime in the early 2000's, depending on the state -- nearly 30 years after its invention. This is very unlike the SARS-CoV-2 vaccine.

> Can you think of any virus even close to COVID mortality that we take these kinds of draconian measures to prevent?

SARS-CoV-1 (2002), MERS (2012+)

"Of the 7 coronaviruses, the former four can cause common cold symptoms, but SARS-CoV-2, SARS-CoV, and MERS-CoV can lead to severe respiratory syndromes, with about 6.76%, 9.6%, and 35.5% mortality rates, respectively." [0]

We just dodged a bullet because they were regionally-contained and/or had lower transmissibility. But if you were in Asia before and after 2002, you noticed.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334925/

Edit: And if we want to go to the more-lethal, less-transmissible end of the spectrum (so roughly equivalent in terms of public health risk), the regularly recurring Ebola outbreaks in Africa. Most recently the 2013-2016 campaign.

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

That paper was a meta-study from July of last year based on papers even older, and it's loaded with problems. This paper in the Lancet [1] and this paper in BMJ on Delta [2] both have mortality at significantly lower. World-o-meter has the mortality rate in New York at 0.28%. [3]

[1] https://www.thelancet.com/journals/laninf/article/PIIS1473-3... (Among RT-PCR-confirmed cases tested by Oct 1, 2020, 342 (2·4%; 95% CI 2·2–2·6) of 14 237 died within 30 days of their positive test. Mortality was 0·4% (95% CI 0·3–0·6) at ages 0–39 years, 2·0% (1·7–2·3) at ages 40–64 years, 7·5% (6·4–8·7) at ages 65–79 years, and 15·4% (11·6–19·6) in those aged 80 years or older (figure 4))

[2] https://www.bmj.com/content/372/bmj.n579 (The absolute risk of death in this group of community identified participants, however, remains relatively low, increasing from 2.5 to 4.1 deaths per 1000 cases.)

[3] https://www.worldometers.info/coronavirus/coronavirus-death-...

You're confusing case fatality rate (detected infection denominator) with infection fatality rate (total population denominator).

The study I cited was (broadly) CFR. That Lancet study is (broadly) IFR. If you proactively surveillance test 13.5% of Madurai's population, you're going to get a different class of people in your denominator, and your calculated mortality is going to decrease.

The BMJ study is probably the most broadly compatible, which leaves us at 2.5% (non-Delta) or 4.1% (Delta), which appears to be case fatality rate?

If we want to argue apples:apples, we should use EMR-based studies that attempt to calculate IFR, as at least they're reasoning with the same population composition.

This [0] has SARS-CoV-2 at somewhere between 0.26% and 0.83% IFR. Which for context, is compared to respiratory flu at 0.0088% (estimated total population EMR due to flu) [1]. So we'd expect about 29.5x as many people to die from SARS-CoV-2 (using the high end estimate of flu and the low end estimate of SARS-CoV-2, to generate the lowest possible multiple). If you want to, you can probably dig European numbers out of this excess mortality calculation [2], although that's all-cause mortality, with no attempt to isolate cause.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543961/

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935243/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346364/

> This [0] has SARS-CoV-2 at somewhere between 0.26% and 0.83% IFR. Which for context, is compared to respiratory flu at 0.0088% (estimated total population EMR due to flu) [1]

Isn't this disregarding (or generalizing) the fact that age plays a significant role with SARS-CoV-2? Those numbers are vastly different between, say, teenagers and 60+ year olds.

I don't see many 60+ running around protesting. Mostly it's the 0.01% IFR crowd.

It could have also been much worse though no? If those 3 days turned into 5 in a hospital with another long tail of lung issues would it still be worth it just not to get jabbed again?

Or rather if those 3 days turned into death.

I'd rather take boosters every year than risk a horrible death.

No matter how small the risk?

At "peak times", it isn't that small - even in my ridiculously small social circle, in Italy, there was one death and a couple of very severe cases. And peak times are determined largely by the pressure on health services, which is determined by vaccination rates (since vaccines remove the need for hospitalization). So it's a vicious circle: if you don't vaccinate, you increase the mortality risk to very significant levels.

By the time you're experiencing symptoms, the infection has been present for some time. Most of the symptoms you experience are from the immune response mounted, but do not represent the time your immune system was exposed to the virus.

There is little evidence right now that immunity through a natural infection is better than immunity from a vaccine.

Given the strains circulating now I don’t think your concern is valid. Vaccines are better and less risky than having your naive immune system deal with covid. Maybe that will change with a future strain (though I’d bet against it), but it isn’t the case now.

> Vaccines are better and less risky than having your naive immune system deal with covid.

Agreed. However, many people are not in that position. For those who have been infected but not vaccinated, they have experienced immune systems and must evaluate information from that starting point.

Except all available safety and efficacy data shows that those who have been infected but not vaccinated should get vaccinated.

> There is little evidence right now that immunity through a natural infection is better than immunity from a vaccine.

This is a very strong claim to make without any evidence or proof.

To the contrary, there is strong evidence that natural infection brings considerably better immunity than any vaccination does. [0]

Study analyzed:

> 2.5 million people in Israel, spanning March 1st 2020 to August 14th 2021.

Full study can be read in detail: [1]

[0] https://www.israelnationalnews.com/news/312538 [1] https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

There is a more recent U.S. study [1], which comes to a different conclusion, and neither of these studies take into account boosters (or a longer delay between shots), which by all accounts improves vaccine effectiveness by ~10x.

Being vaccinated and then boosted offers as worst equal protection, probably better, against infection and disease, with much much lower risk of side effects, serious disease, long covid or death.

1: https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7044e1-H.pdf

That's an unbelievably poorly designed study, for many reasons.

It basically says unvaccinated people who are already or recently sick (with any "covid-like" symptoms) are more likely to go to the hospital once they catch covid (vs vaccinated). (Duh.)

Worse, it presumes any of those sick people with respiratory symptoms had natural immunity to covid without any confirmation.

So it's not comparing natural immunity to vaccinated immunity, but vaccinated individuals vs anybody-unvaccinated-thats-been-sick-with-anything-in-the-last-6-months.

Put another way, it presumes any "covid-like" symptoms results in natural immunity to covid, then puts that assumption to the test.

And instead of admitting it's a bad assumption and that most of this group didn't previously have covid, they attribute it to natural immunity not being effective.

Your interpretation of the study is wrong (and probably shows your internal bias in this matter).

I’m not suggesting it is a perfect study, but the methodology makes sense. The point is that if somebody gets hospitalized for covid-like sickness, then they’ll be hospitalized (and trackable), and they hope that is a stable cohort.

So you start with hospitalized patients with covid-like symptoms, then look among them and see who was vaccinated (and when), vs who previously had covid (and when), and then by looking at the percentage of cases caused by covid you are attempting to effectively compare the susceptibility to covid in the broader population. It works as long as the person is getting all of their medical care in your system and you have full tracking of them (which they do in the study).

And again, it isn’t perfect but there is no perfect study for this. And when they redo the study with boosters whatever the result is we know the real world effectiveness of boosters is 10x non-boosted do the results would be even better.

You start out by saying their interpretation is wrong, but their interpretation is that it:

> presumes any of those sick people with respiratory symptoms had natural immunity to covid without any confirmation.

This is an accurate statement to make about the study. Until you can effectively prove somehow this is not the case, it's only you who

> shows your internal bias in this matter

No it doesn’t. Read the study. People being hospitalized with covid-like symptoms is the broader population and those with prior confirmed covid infections and those with prior confirmed vaccines within that population are the sample groups where the covid infections rates are compared.

Do you genuinely believe a study with such a massive and obvious methodology problem would get published and cited by the CDC? (and yes I know bad studies do get published from time to time but it isn’t common).

I read the study, it's a few pages-long PDF with no description of computational methodology, no indication of the statistical approaches taken, and no justification for the arbitrary decisions made by the people who carried out the study.

The criteria for inclusion in the study:

> Hospitalized adults aged ≥18 years with COVID-19–like illness were included if they had received testing at least twice: once associated with a COVID-19–like illness hospitalization during January–September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization).

This is a terrible methodology. It says nothing of a positive or negative test result, and the duration of time in between hospitalization and testing is absurdly arbitrary. It is simply assumed to be a COVID infection with no reasoning for this decision.

We've then got this nugget:

> Laboratory-confirmed SARS-CoV-2 infection was identi-fied among 324 (5.1%) of 6,328 fully vaccinated persons and among 89 of 1,020 (8.7%) unvaccinated, previously infected persons

Perhaps they should have found 5,000 more unvaccinated people before concluding their study. They are not hard to find.

> Do you genuinely believe a study with such a massive and obvious methodology problem would get published and cited by the CDC?

This is a joke, right? The CDC are frequently derided for their terrible methodologies and this goes back for decades. Not an uncommon outcome where you are an inherently political organization that is also in charge of distributing enormous sums for research funding. So of course, I would expect a terrible study like this from the CDC.

You're actually going to compare this crap-tastic shitfest of a study with the rock-solid study I provided, containing ~3mil participants and a far more verbose & informative outline of the study's methodology?

From page 1:

> Previous infection was ascertained based on SARS-CoV-2 testing from rapid antigen tests or molecular assays (e.g., real-time reverse transcription polymerase chain reaction) performed before mRNA vaccination and ≥14 days before admission; testing performed after February 2020 was primarily within network partners’ medical facilities.

>Your interpretation of the study is wrong (and probably shows your internal bias in this matter).

They claim to be comparing efficacy of natural immunity to that of vaccination, but they're not. They're not really "measuring" prior natural immunity at all, but just assuming it's there.

How's that misinterpreted?

That's not even close to "not a perfect study".

Yet it's being presented, like here, as evidence against the efficacy of natural immunity, which is something it's not, and as being applicable to the general public, when the sample population is self-selected to be only the sickest of the sick (2 hospital visits in a year).

Different is not the same as better. Multiple studies show benefits for each under different conditions such as time since exposure and consistency of protection. The best fit for available evidence seems to be that getting COVID (or at least a positive test result) doesn’t guarantee a robust long term immunity for every individual. But it can result in a better long term immunity for many.

This is why it’s recommended for people to get vaccinated even after infection. They might already have robust immunity, or they might not. The vaccines are so incredibly safe and cheap it’s simply not worth the risk.

https://www.science.org/content/article/having-sars-cov-2-on...

> The natural immune protection that develops after a SARS-CoV-2 infection offers considerably more of a shield against the Delta variant of the pandemic coronavirus than two doses of the Pfizer-BioNTech vaccine, according to a large Israeli study that some scientists wish came with a “Don’t try this at home” label. The newly released data show people who once had a SARS-CoV-2 infection were much less likely than never-infected, vaccinated people to get Delta, develop symptoms from it, or become hospitalized with serious COVID-19.

From the same article:

> The researchers also found that people who had SARS-CoV-2 previously and received one dose of the Pfizer-BioNTech messenger RNA (mRNA) vaccine were more highly protected against reinfection than those who once had the virus and were still unvaccinated.

Yes, and?

The comment to which I'm responding said there's little evidence that natural immunity is better than vaccines. That's just not true. There's pretty strong evidence, actually.

That natural immunity plus a booster is better than either is interesting, but not responsive to the question.

No there is not strong evidence. The Israeli study highlighted previous infection versus vaccinated but not (yet) infected. Note the "previously infected" category did not exclude the vaccinated, but the vaccinated category did exclude the previously infected. The only solid conclusion to make from that is: that even if you have been previously infected, get a vaccine.

> The Israeli study highlighted previous infection versus vaccinated

Yes, they did this, and showed that natural infection was superior to vaccination alone.

> but not (yet) infected.

Incorrect.

> Note the "previously infected" category did not exclude the vaccinated, but the vaccinated category did exclude the previously infected.

No. You only have to read the link to see that your understanding of the study is entirely incorrect.

> The study...found in two analyses that never-infected people who were vaccinated in January and February were, in June, July, and the first half of August, six to 13 times more likely to get infected than unvaccinated people who were previously infected with the coronavirus. In one analysis, comparing more than 32,000 people in the health system, the risk of developing symptomatic COVID-19 was 27 times higher among the vaccinated, and the risk of hospitalization eight times higher.

Okay. I admit that my characterization was sloppy/incorrect. Thank you for pointing that out. The paper is still not strong evidence though. To whit:

"the higher hospitalization rate in the 32,000-person analysis was based on just eight hospitalizations in a vaccinated group and one in a previously infected group. And the 13-fold increased risk of infection in the same analysis was based on just 238 infections in the vaccinated population, less than 1.5% of the more than 16,000 people, versus 19 reinfections among a similar number of people who once had SARS-CoV-2."

These numbers are very small for distinguishing between the effectiveness of two different and effective immunization methods (natural and vaccine). By now, we should have more data to support if the effect size is that strong. Do we?

Even if the numbers scale up, they'd mean that you'd avoid roughly 1 hospitalization for every 2285 people who got immunity from being infected instead of from being vaccinated. Unfortunately, to obtain that immunity, about 1 in 30 had to be hospitalized, 1 in 250 died, and a significant number suffered serious complications.

Nobody in their right mind would choose such a tradeoff.

Nobody here is making this argument. You're setting up a straw man.

The point is: people who have recovered from the illness are immune, and should be treated as such.

> people who have recovered from the illness

I'm not sure the guy on the street is actually interested in properly understanding the risks associated with Covid.

My neighbour is in his 70s, he had Covid in November 2020 and (in his words) he wasn't particularly poorly with it. He subsequently had his vaccinations.

He and a couple of friends have been having blood tests to check on antibody titres. His antibodies are still really high, his friends (who haven't had Covid) have antibodies which have dropped significantly since they were vaccinated. He told me he wasn't sure why.

We were talking out on the street, my kids were out and around on their bikes, he told me he thought it was really important that children (like mine) should get vaccinated in order to keep people like him "safe".

What do you say at that point? I'm honestly not sure where we go from here.

> These numbers are very small for distinguishing between the effectiveness of two different and effective immunization methods (natural and vaccine). By now, we should have more data to support if the effect size is that strong. Do we?

You should check the number of deaths in the original trials used to approve the Pfizer and Moderna vaccines. You might be surprised. Even in big trials in immunologically naive populations, only a small number of people became seriously ill -- a total of 10 people became seriously ill across the entire Pfizer trial. No deaths occurred. [1]

Once you've vaccinated your population (or otherwise allowed them to become immune), you're talking about incredibly small effect sizes.

[1] https://www.nejm.org/doi/full/10.1056/nejmoa2034577

Doesn't that literally have survival bias baked into it? The people that survived COVID-19 are going to be more fit as a population than the population that didn't have the deaths.

Even if they were, why would you assume this would be relevant to re-infection?

The vast majority of people testing positive for the virus are not dying from it.

What does 'better' mean to you?

I am in relatively lower risk group, and in good health. I got it and recovered on my own. I got blood test and have Dr. letter to prove it.

It appears I now have sterilizing immunity, which is not available with the present vaccines. I suggest sterilizing immunity is better for everyone around me.

Bullshit of course. You can get COVID multiple distinct times, with or without a vaccine

I got vaccinated because I didn't want to die from COVID. I'm okay with getting an annual booster, as I am with getting an annual flu vaccine. The risks of not getting vaccinated were too high for me to accept.

I'm still interested in how resistance to the disease emerges in the unvaccinated population. It will help to inform our response to the next pandemic.

Isn't the reason a vaccinated person's immune system might not specialize to wild covid as much during infection as an unvaccinated person's that the disease in the former is shorter lived? Like, the way the never-vaccinated person would get slightly lower risk in the future is by taking a much larger risk now. You're still way better off with the vaccine.

Also selecting for survivors.

In the group of vaccinated survivors there will be more folks who would have died from infection without the vaccine, because of insufficient immune response.

People who survived an infection without prior vaccination are more likely to have a good immune response to the disease.

We get flu vaccine every year, what's wrong with getting vaccinated forever?

Who's "we"?

I don't intend any hostility here. But I have never gotten a flu vaccine in my life, and it seems deeply silly to me to get a yearly shot just to cut down on the chance of mild illness. A quick poll of my acquaintances reveals that almost no one in my social circle gets flu shots, either. This makes me wonder whether the antagonism to mandatory COVID boosters is just an intensification of an existing divide between people who already get yearly jabs and people who don't, a divide which was mostly unobserved until now because it wasn't politically relevant.

(Minor grammatical edits.)

> it seems deeply silly to me to get a yearly shot just to cut down on the chance of a mild illness.

Is it silly to get a shot in order to cut down on the chance of someone else having a mild illness turn severe or fatal?

"We" are people intelligent to recognize that vaccination against diseases like the flu is a good idea even if we're healthy and unlikely to have significant complications. "We" know that the shot will make it less likely for us to get sick, and that we're more likely to have a mild case if we do get it after being vaccinated. "We" also recognize that getting vaccinated helps reduce the number of people who spread a virus that can be deadly to other members of society, particularly the very young, very old, and those with compromised immune systems.

Getting vaccinated not only helps yourself, it helps those around you.

"You are not intelligent because you make different personal medical decisions than I do."

Indeed. Every time I read a post like the grandparent I move closer to full-blown antivaxx.

Pedantically, basing your stance purely on being tired of being told what to do _isn’t_ an intelligent strategy. Not saying that’s your entire stance, but emotional contrarianism is not a good reason to update your priors.

It can move you closer to an environment where you aren’t often told what to do, though.

It doesn't help when that thing you're being told to do is constantly changing, and in addition doesn't seem to change where it matters. It seeds doubt and uncertainty, which is surely what we're seeing all around us. No one knows what to do with Covid. And those who claim they do for certainty are sure as hell full of shit.

I was in the military for years. Vaccines galore for any and every conceivable illness. I was required to have flu shots. Every single flu shot I've had gave me the flu. Full blown sickness, within a day of receiving the shot. Since leaving the military I've not had a flu shot and I've not had the flu. Obviously it's anecdotal but you'll never convince me to start taking flu shots after such repeated experiences.

That's not how flu shots work. You might have had an immune response that had you feeling down, but flu shots don't give you the flu.

It's semantics whether or not full-blown flu symptoms are "the flu" or not; I get the flu shot, then I get sick.

Except you aren’t going to risk getting very sick (pneumonia) from the vaccinated response. And you aren’t going to give the virus to someone else.

Enjoy your moral superiority, and I'll enjoy not feeling like dog crap for a week after getting the shot.

I find it insane that someone would argue against your personal experience like that.

I've had the feeling all along that once we've started getting people forced into perpetual Covid vaccinations it's gonna move into seasonal influenza vaccines. Judging by this discourse my hunch is not far off.

Why engage in discussions when semantics does not matter?

Technically I think your reaction is from the immune response to the vaccine. Which is unpleasant but not contagious.

Now real flu viruses may have not yet given you symptoms since you stopped vaccinating. But it's possible you're becoming a carrier of the virus that spreads it to more vulnerable people. Some of whom may not be able to get vaccinated.

It's my choice not to take shots that make me sick, and no I won't take them again. It's unfortunate that some people have fragile health, but it's not really my problem. No amount of brow-beating will make it my problem. No, I'm not a calloused individual that doesn't care about others. I don't believe that anyone is required to undergo medical procedures in order to benefit me, and I will not undergo medical procedures for anyone else, especially considering my experience with those procedures (significant illness, every time).

Mind you, you sound 100% like someone who do not care about others.

But your decision to not take flu shots sounds totally reasonable given you apparently get a bad adverse reaction every time.

You therefore belong to that group of people whose health is too weak to get vaccinated, I guess.

I hope you won't catch the flu, and will keep getting vaccinated whenever I get the chance since I'm lucky enough that I've never felt any illness from any vaccine (but got flu once and had to stay in bed, half unconscious, for almost a day).

I don't know what high horse bubble you live in, but in my almost 40 years on this planet I've only met one single person who has ever had a flu shot and he's younger than me. Granted I have to live in another kind of bubble. My currently 70+ year old parents and aunt, as well as my 80+ old mother-in-law, have never had a flu shot (until my aunt this winter).

It definitely has nothing to do with "not caring about others". What a malicious human being you seem to be. The vast majority of people just aren't that worried about the flu. It's a natural part of life for most people. For old people and immunocompromised it's relevant, and for them it's obviously their choice to defend against it - and I've started recommending elders in my community to get flu shots (if they want!), even though it only has around 40% efficacy.

Vaccinating kids or young people? Wow. I was sacked for 2 days both with my first and second jab. Next one I'm just gonna let my immune system ride it out. Arrogant people like you convince me.

Well.

The flu isn't always mild, especially as you get older. Depending on the year a couple hundred thousand Americans wind up in the hospital and about 10-20k die. [1] Compared to COVID-19 (hence the "politicization of getting the vaccine) it's not that bad but it's still not great.

Now what is the cost of getting a flu vaccine every year? Well, for most people it's 0. You walk in, get a shot, walk out. Arm is sore for a day or two at most and that's it. Then in getting the flu shot you reduce your own chance of getting the flu and reducing severity if you do get it anyway (which many people do), and you lower the risk for others who might be immunocompromised, susceptible to the flu, etc. Now I understand if you want to make the case that society shouldn't pay for it or that it's not worth it or w/e, but on an individual level there seems to be a ton of upside versus the downside.

So what's the downside of the flu shot? You're inconvenienced. That's about it. Unfortunately it's hard to measure the value of that inconvenience versus the upside, so, as typical human nature goes, you just value your inconvenience and then decide not to get a flu vaccine. Unfortunately it's just human nature. The same human nature manifests in all sorts of "I got mine" kinds of ways, ranging from global warming to opposing healthcare for all (why don't they just get insurance like me?).

If anything I think the dividing line isn't so much political (though it's now being used politically), it's who is willing to make sacrifices for the good of society. In the case of the flu vaccine here what I'm hearing you say is basically "welp, I don't see how it benefits me so I don't care". Is that not the case?

> it seems deeply silly to me to get a yearly shot just to cut down on the chance of mild illness

As someone who now just grabs the flu shot whenever it's available and I happen to be in a convenient spot the 1-3 days I might feel like crap seem like an awfully high price to pay for not getting a shot that takes 5 minutes. At least practically speaking. Idk. I don't like getting sick and the shot doesn't bother me at all.

[1] https://www.cdc.gov/flu/about/burden/index.html

I got the flu when I was in my late 20s. Up until that point, in common I suspect with most teens and twenty-somethings, I had thought myself pretty much indestructible, so would never have even thought about getting a flu vaccine - I thought that was only for the old and vulnerable. However, since that experience, I try and get one every year - even if you are young and healthy it can be pretty rough, and why risk having to go through that again if you can avoid it?

To the GP's question, about whether catching something gives you better protection than having a vaccine, my (non-expert) expectation is that Covid is like the flu - my having had the flu won't give me protection for all future strains, so I'll keep on needing new vaccines periodically for those new strains.

> about whether catching something gives you better protection than having a vaccine

It's also medically incorrect. When you get a vaccine you are literally getting a live virus injected into you. There's no difference for your immune system. One isn't "fake" and the other "natural". Period.

To your point, viruses mutate and so similar to the flu and flu vaccine, if COVID-19 continues to mutate in ways that are different enough we'll have to get new COVID shots which use modeling to predict the likely virulent strains. People that are aghast about this concept are not really understanding the new reality we're in. The only hope is that if enough people get vaccinated quickly enough, a new strain won't mutate and cause the vaccines to lose some effectiveness. I think that's a wildly naive hope, though and the best path forward is just treating this like a worse flu and moving on with our lives.

> When you get a vaccine you are literally getting a live virus injected into you.

This is false for the mRNA vaccines according to the CDC:

mRNA vaccines do not use the live virus that causes COVID-19 and cannot cause infection with the virus that causes COVID-19 or other viruses.

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different...

Correct, though the "natural" vs not still applies here. There's no evidence or scientific reason to suggest that catching COVID-19 naturally provides any different immune response than receiving the vaccine for the same strain.

In my previous comment I was unclear about what I was addressing and when, though ultimately the point is that this distinction of contracting a virus "naturally" versus "artificially" is not scientifically based. Applies to COVID-19 mRNA vaccines as well as flu vaccines.

If there's evidence to suggest otherwise though we should get that out there.

> mRNA vaccines do not use the live virus that causes COVID-19

That has caused resistance among friends I know, who say that its not a real vaccine, since vaccines give you a small dose of a live virus to trigger one's immune response. Perhaps the mRNA injections should have used a different name to clear misconceptions.

Either you’re using the medical definition of mild (didn’t require hospitalization) or you haven’t gotten a true influenza infection in a long time. So many people call strong colds a “flu”, which creates confusion around its severity and contributes to people avoiding the vaccines. But real influenza will have you in bed for a week and set back your fitness for a month (making you tired after even moderate exertion).

Getting my first real flu since childhood is definitely what got me back on the vaccine train. All this talk about mortality, I want to minimize even basic inconvenience to myself!

It is exactly that, a divide between people who already get yearly jabs and people who don't.

What is new is that those who get yearly jabs, now wants to mandate the other group to get yearly jabs.

This is what I never want to see happen, we should have as much control as possible over our own body.

First of all, "we" don't all get the flu vaccine every year. Those of us who are healthy can elect not to get it and be just fine.

Secondly, the flu vaccine isn't the same vaccine every year. It is reformulated to target the flu strains that are predicted to be dominant that season.

Thirdly, the flu vaccines effectiveness varies wildly from pretty darn good to almost worthless. Usually depending on how accurately flu strains were predicted.

You cannot "elect" to not get a vaccine and be just fine. You're just relying on your luck after electing not to reduce the risks.

The risks vary with different diseases, and in different people, and in different demographic environments. But with covid, it's quite clear that for all adults, the risk reduction by vaccine far outweighs the risks of vaccine complications.

Risks of vaccine complications are not the only risks to weigh against getting a vaccine.

Now that these are being mandated it also becomes a risk of validating medical tyranny as an authoritarian methodology.

Is it tyranny if it’s what the majority wants and votes for? It seems like “tyranny” is being used to describe situations where democracy is working as expected, and some people just don’t want to accept the majority result. I feel like this word tyranny is being thrown around a lot lately without much rigorous thinking about the fact that we do need laws because we have no choice about having to share a lot of things including the air we breathe. Is the fact that it’s illegal to murder someone tyrannical and authoritarian?

How much of your comfort in these drugs is based on who is holding power wherever you may reside?

I don't really know what you are talking about with the murder analogy. Obviously the uncomfortable issue at play here is the duality of:

Your right to swing your arms ends at my face or whatever.

Who's doing what to who here? Are you punching me with the mandate or am I punching you with my hypothetical infection and hypothetical ICU bed? Do we have to put numbers to how hypothetically infectious I am or we must fall in line and "Do whatever we can" which today happens to be getting injected with a drug that fails to prevent infection.

> How much of your comfort in these drugs is based on who is holding power wherever you may reside?

Literally zero. I know enough about science and economics to know that the US president has no bearing on the efficacy of the COVID vaccine whatsoever, just like politicians have exactly zero bearing on how well the flu vaccine works or how well Ibuprofen works.

> Your right to swing your arms ends at my face or whatever.

Right, so why in your mind doesn’t that extend to my right to not get infected by you in public?

P.S. you dodged the question: why is a mandate that the majority wants equivalent to tyranny? Do you think the mandate to buy car insurance in order to drive on public roads is tyranny?

Oh you mean the Americans who think they have a 15-25% chance of dying from Covid if they get it? I wouldn't trust the majority to be well-informed.

https://covid19pulse.usc.edu/ (granted the numbers have been going down recently, but it still illustrates the hysteria quite well)

And I also wouldn't trust big pharma to have my best interest in mind.

> Oh you mean the Americans who think they have a 15-25% chance of dying from Covid if they get it?

Absolutely not. I meant the total number of people who have actually died from it compared to the near zero vaccine fatalities.

Your question (not me though, but) was:

> why is a mandate that the majority wants equivalent to tyranny?

I doubt the dead people (the vast majority being 60+) are the ones mandating it.

It's the same people who think it's imperative that we vaccinate children when a) children are barely affected by the virus b) the vaccine doesn't do much for the transmission rate anyways.

And if that's a majority then the majority is simply misinformed (or stupid).

> I doubt the dead people (the vast majority being 60+) are the ones mandating it.

What’s with the silly straw man? Your last comment was a straw man too. I’m interested in a rational discussion if we can have one. Are you uninterested in that?

> if that’s a majority then the majority is simply misinformed (or stupid).

Then it seems like you’re saying the vaccine mandate is not tyranny, it’s just in your opinion stupid people, right?

This may be relevant to your question: https://en.m.wikipedia.org/wiki/Tyranny_of_the_majority

Do you believe this is what parent was referring to? I must assume not because they used the word “authoritarian”, which implies they’re complaining about minority groups imposing their will on the majority.

Do you believe that Tyranny of the Majority is a valid concern with the vaccine mandates? Which minority groups are being oppressed?

I can't speak for parent, I'll leave that to them. I just meant to show evidence that because something is approved by the majority doesn't disqualify it from being tyrannical.

Personally, I don't see why it wouldn't be a concern with the mandates, but I think this conversation has already been repeated by others ad nauseum:

I say bodily autonomy, you might say we mandate all sorts of vaccines, I say these aren't those vaccines, you might say well they're safe and effective, and I say talk to me in 5 or 10 years when we have long term data, and you might say well we've never linked adverse effects to previous vaccines after n days, to which I'd say good luck actually finding those impacts if they do exist and again these aren't those vaccines, and we eventually arrive at a difference in beliefs/biases and an impasse.

> I say bodily autonomy, you might say we mandate all sorts of vaccines […] talk to me in 5 or 10 years when we have long term data

It’s strange to me that the arguments against vaccines are all self-centered, about personal risk, and the arguments in favor are all addressing net social benefit. I kinda want the bodily autonomy to not get infected by someone refusing to take any social precautions over political beliefs.

We have more than enough data already, enough people have died from COVID, to prove the vaccine is a net benefit to society, and enough data and solid evidence to know that the personal risk is much lower than the risks that come from getting COVID.

> because something is approved by the majority doesn’t disqualify it from being tyrannical

We’re talking about something specific, not vague platitudes. Tyranny is defined as being oppressive, arbitrary or cruel assertions of power. None of that is true for the COVID vaccine.

We're going to have to agree to disagree on your usage of autonomy there, but your point is taken. We should be looking out for each other, and I think you'd find that a lot of people probably are, even if they disagree with you about various covid/vaccine issues.

Regular testing, distancing, masking, foregoing normal activities are examples of other ways to look out for each other. Maybe I'm crazy, but I think we'll eventually find that folks who just got vaccinated and went about life like normal probably caused more spread than folks who didn't but kept up all the other precautions. I think if you assume everyone thats going about it differently from you is selfish, you're going to be missing chunks of the picture.

> We have more than enough data already...

And this is where we find our difference in beliefs/biases. Same for your opinions on what is and isn't tyranny, which you're welcome to.

> I think we’ll eventually find that folks who just got vaccinated and went about life like normal probably caused more spread than folks who didn’t

Why do you believe this? What evidence do you have to ignore the overwhelming conclusions of all the experts actually studying the disease and the vaccine? The idea that vaccinations cause more spread has in fact been studied on the COVID vaccine and on others. It’s generally not true for most vaccines, why do you think it’s true for this one?

Why are you talking about spread and not also hospitalizations and fatalities? The vaccine considerably lessens the risk of dying. Even if the spread rate were to increase a little (which I don’t really buy), but the risk decreases by an order of magnitude, isn’t a lower total death rate a social net benefit?

How many people have died of COVID to date? How many people have died of COVID vaccines so far? Seriously, please find and compare those two numbers.

Tyranny is defined in many dictionaries. It’s not my opinion, the word has a specific meaning. You haven’t answered the question of why a vaccine mandate should be considered tyranny, or how it compares to any other case of action mandated by law, or personal freedoms limited by law, of which we have many.

It would be lovely if anti-vaxxers were distancing and wearing masks, but that seems like a fantasy to me. How many anti-vaxxers really are wearing masks and taking all other precautions? There seems to be a lot of data that there’s a large correlation and significant overlap between people who are anti-vax and anti-mask and anti-lockdown. We had the chance to stop COVID spread, and we bungled it by politicizing the solutions, people are screaming tyranny over mask mandates and social distancing mandates too.

> the overwhelming conclusions of all the experts actually studying the disease and the vaccine?

Forgive the snarkiness, but do you have some sort of machine that knows who all of the true experts are, and figures out the sum of all of their knowledge? Even better if it comes with daily updates. I'd love to borrow it if you do.

My point is you yourself would have to be an expert to be making the assertion that you're making. Are you? If not, it comes down to us just trusting different sources. I personally like published literature. I don't like the news or Twitter personalities or bureaucrats.

That aside, I think you're responding to something I didn't (or at least didn't mean to) claim. I'm not saying the vaccine itself makes you spread covid, I'm saying I wouldn't be surprised if the people who heard "safe and effective" and thought "great, no need for any of that other stuff, let's party!" [Edit:] might be generating more cases than someone who takes every other precaution.

I believe this because there is published evidence that these vaccines only reduce spread, they don't stop it. (More exposure + some reduction in transmissibility) could be greater than (minimal exposure + full transmissibility). I'm not claiming this is fact. It's just the prediction of some dummy on the internet.

> Why are you talking about spread and not also hospitalizations and fatalities

Can't have hospitalizations or deaths without spread. I'm talking about looking out for each other here, the social good that you referred to. If my own personal odds of spreading to other people is low enough (for example because I regularly test and have previously recovered, and all the other precautions I mentioned), I've done my part. If someone is vaccinated but engaging in high risk activities, I've done more than them.

> Tyranny is defined in many dictionaries

Lots of things are defined in the dictionary. It's then on us humans to interpret them and apply them. I'm not necessarily saying the mandates are tyranny, I'm saying they could be. The mandates may turn out to be illegal. If they do, that might be considered the president unlawfully enforcing rules, which to some might be considered tyrannical.

I'll bite. First of all I don't think vaccine mandates are "tyranny", just stupid/stubborn (and in the some cases virtue signaling).

> The idea that vaccinations cause more spread has in fact been studied on the COVID vaccine and on others.

The studies done since at least August (after delta) suggest that the vaccine doesn't do much for stopping transmission. For example: https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

> Why are you talking about spread and not also hospitalizations and fatalities? The vaccine considerably lessens the risk of dying.

It all boils down to hospitalization. The problem here is that the vast majority of hospitalizations are old people and/or with co-morbidities. Vaccinating young and healthy (or children) does very little to help this (except line the pockets of pharma companies (and politicians if you believe in conspiracy theories)).

I got two jabs because I was under the false impression (as were many others) that I'd be protecting my parents (and other members of society), but now since that's out of the window thanks to delta (and omicron lurking behind the corner) I see very little reason to get a lifetime Pfizer subscription.

> It would be lovely if anti-vaxxers were distancing and wearing masks

Given that I've had two jabs but am strongly considering not getting a third, does that make me a pro-vaxxer or anti-vaxxer? I'm fairly young (in my 30's) and in good health. I'm not worried about Covid. I'm worried about older members of my family getting it and have recommended them 3rd jabs. For me, no thanks.

Re: masks, it's difficult to speak about this (due to being labeled an "anti-vaxxer" or "spreader of misinformation"), masks don't ultimately don't do that much. Assuming you're socially distancing you're already protected against droplets, and against aerosols you'd have to use N95's to get any kind of protection. Sure if someone is talking to you directly (or coughing at you) wearing a mask makes sense. But by that logic it means that we should be wearing masks everywhere (unless we stay isolated) for the rest of our lives. Not an attractive option.

We all hoped vaccines were gonna solve this, but the situation we're facing now is one of denial, where no one is prepared to admit that we don't know what to do, so governments are panicking and hoping that vaccine mandates or Covid passports are going to do anything other than make already angry/scared/frustrated people more angry/scared/frustrated. Hint: It won't. Covid is here to stay.

People are yelling "pandemic of the unvaccinated". Think ahead a bit. If we were to get to 100% vaccination rate, which is practically impossible, it would just become the "pandemic of the vaccinated". Which kinds of variants would we be worrying about then?

Which leads into the fact that research shows (as logic also dictates) that natural immunity offers better protection than just that of the vaccine. I'll take my chances and let my immune system do the work, thankyouverymuch.

We don't force fat people to go on diets either, even though they're a burden on the healtcare system. And here in Europe we have to pay taxes for their healthcare as well. We accept that.

> We had the chance to stop COVID spread

Did we, seriously? It's becoming increasingly clear to me that there's not really much we could do after maybe March/April 2020. We can only mitigate the damages, try to protect risk groups. And that's what we should be focusing on. Not broad senseless measures like for example Covid passports.

As a young, healthy person you don’t get the flu vaccine to protect yourself, you get it to lessen the chances that you’ll pass on the flu to someone elderly or immunocompromised for whom the flu is often deadly.

This is how vaccines work toward public health. Not by preventing illness in all cases, but by lessening the pool of potential cases to ease the health burden on the population.

It’s good practice as a citizen and a neighbor to get vaccinated.

Many vaccines do not prevent transmissibility.

Huh. The CDC says that about 50% of adults in the US get the flu shot.

That's much higher than I would have guessed. I would have thought it was around 20%... medical workers and the old/infirm. I never have; I might when I get into my 70s or 80s.

It's a different vaccine every year, because the "flu" virus family mutates extremely much, for (at least to me) unknown reasons.

note that it’s not that the flu virus mutates so much more than other viruses, as it’s using the same (imperfect, mutation-inducing) machinery to replicate itself as other viruses, it’s that its genome is sufficiently resilient to mutations that more variations can survive to infect others. perhaps there are many more, or just more flexible, non-critical regions that can be swapped out willy-nilly without damaging the core replication function. or the replication-coding regions of the genome can be swapped around more easily without ill effect. or there’s more error-correcting. or a number of other plausible mechanisms than being better at mutating, because that’s unlikely.

You had the vaccine so you recovered quickly, if you didn’t have the vaccine you might not have recovered and needed hospitalization.

I mean, the alternative where you don’t get the vaccine includes much higher risk of lung damage, nervous system damage and total organ failure.

I think even if there was data to back this up (that somehow vaccine gives less protection than a real infection…), getting a booster every year or 6 months is well worth it given what happens with an unvaccinated covid infection. People do seem to get reinfected and die after already having it once.

I don’t think that your model of how vaccines work really makes sense. I mean, the point is to prime your immune system with antibodies to something similar but relatively harmless so you can fight off the disease immediately rather than waiting for it to get a strong foothold… in a way that is safe.

Saying it is less effective than getting sick is like totaling your car to avoid regular maintenance.

Except for many cohorts, the overwhelming — near certain — odds are that they’d be fine after contracting COVID.

Why draw a deadly roulette ticket?

Because this:

https://www.forbes.com/sites/adamandrzejewski/2021/11/04/fed...

despite this:

https://www.youtube.com/watch?v=lepqvdXoA2E&feature=youtu.be

Oops, you can't watch that. Senators holding an expert panel is "dangerous misinformation". Here you go:

https://rumble.com/vokrf7-sen.-johnson-expert-panel-on-feder...

Just so it is clear to you, the Forbes article you link is an opinion piece.

Premised on the undisputed fact that vaccine manufacturers are not liable for adverse reactions, leaving the victim with no remedy.

Just so it's clear to you, there are facts in opinion piece. Opinion pieces are often someone's opinion on existing facts.

Seems like the vaccine is the deadly roulette ticket: risk of fatal bloodclotting every time a new vaccine is administered while ironically being at a higher risk against new, potentially more dangerous, mutations compared to people who recovered from a Covid infection naturally. I guess it comes down how much you trust pharmaceutical companies having the payday of a lifetime and politicians on a power trip.

To be clear, there is no evidence for any of your claims.

Risk of blood clotting / thromosis (VIIT) with adenovirus vector and Peri / Myocarditis with mRNA based are known risks, even if extremely rare overall (but worrying for specific groups; <50 females and <30 males respectively)

You should compare with risk of clotting vs covid disease.

In which case….why care which order you did things in, by your logic? If the consequences are low the decision is academic.

(I don’t agree: I think there is risk of chronic damage that doesn’t appear as acute symptoms)

> I don’t think that your model of how vaccines work really makes sense.

I believe OP is referencing "Original antigenic sin" [0].

"This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections."

[0] https://en.m.wikipedia.org/wiki/Original_antigenic_sin

Doesn’t make sense. If the infection continues the immune system will generate new antibodies and responses. After all it’s a new thing not seen before.

The linked article both describes the mechanism and has plenty of recent references observing and studying the effect whether or not you think it makes sense.

The general mechanism is that recognition of the antigen by memory B cells produces a response that also inhibits (non-memory) B cells from reacting to the antigen. So when the antigen has drifted enough that memory B cells still recognize it, but the antibodies are less effective then at that point B cells are actively inhibited by the memory B cells so new and retargeted antibodies are not produced.

So, down the line, you might be more susceptible to a similar mutation. (Based on no hard evidence for this particular virus).

(Social media reports aren’t exactly reliable and everything seems to indicate that your chances of serious complications are worse without a vaccine).

Right now, there’s a deadly virus going around and there might not be a “later” for me if I don’t get the vaccine. I think I’ll take my chances with the vaccine. It seems like a no brainer to me.

There is hard evidence. I’m on mobile and can’t look well now, but I encourage you to look!

Eventually you clear the infection in most cases. How do you think that happens?

It happens the same way. This is just talking about rates. When naive B cells see that existing antibodies are already present on the virus they take that as a signal that memory B cells already exist and the search for new antibodies is called off. So there's a balance between the quantity of virus, how quickly the virus replicates, quantity of antibodies, how well the antibodies bind to the virus, and how many bound antibodies are needed on a virus to suppress the naive B cell response. Basically, if binding becomes less efficient you'd expect the viral load to have to get higher before naive B cells get significantly involved. And in fact the infection may just be cleared without involving naive B cells, but just take a bit longer. It seems unlikely that would be worse than not being vaccinated, but I'm sure the devils are in the details of all these factors.

> When naive B cells see that existing antibodies are already present

I don't think this is how this works.

They "see" antibodies sticking to a target, as successful antibodies are presented for replication and refinement. This implies a functional response. If the vaccine antibodies wouldn't work on a new strain, the B cells wouldn't recognize them as suitable candidates.

If this was true vaccines would be ineffective against Delta and other mutated variants, but it turns out the vast, vast majority of cases that are severe or result in death are among the unvaccinated.

This is just bad science and isn't supported by real-world outcomes.

Also adaptation of antibodies evidently works, as cross-vaccination schemes improve response rates. E.g. 2 doses Moderna, then 1 dose BionTech and vice versa, is better than 3 doses of the same for either one.

https://twitter.com/Karl_Lauterbach/status/14516437827855564...

I thought about this a bit more… there’s no reason this wouldn’t apply to a secondary infection with a different strain of covid is there? I don’t see what’s special about the vaccine that would make this effect noticeably worse than simply being infected twice.

> whereas if I had just gotten COVID without the vaccine maybe I would be set

You might be "set" with long COVID, sure [1]. It's like wishing to be mugged so you can learn to fight the muggers next time you get mugged instead of practicing mugging defense with say, a martial arts teacher.

The act of being mugged could injure you for life or kill you.

[1] https://www.nbcnews.com/health/health-news/monumental-acknow...

… well a good martial arts teacher would tell you to either run away if possible or give the mugger your wallet, no?

What do you think a “proper” immune response entails exactly?

Keep in mind that reinfection was always still possible after getting Covid, regardless of vaccination status.

Long-lasting original antigenic sin (e.g., an immune system trapped for years (or forever) in a sub-optimal state by a vaccination event) is a very unlikely scenario. I don't think we have ever seen something like that for any other virus? So, it's no surprise you haven't found much data. I would also suggest you critically examine whatever data you have found that supposedly backs up this concern of yours.

Long-lasting original antigenic sin is well documented at least for dengue.

"Original antigenic sin has the advantage that a response can be rapidly mobilized from memory. However, the downside is that in some cases, such as dengue, the response is dominated by inferior-quality antibody. In influenza, original antigenic sin has been shown to reduce the effectiveness of vaccination (13, 34, 51). In dengue, the effect of original antigenic sin has considerable bearing on vaccine strategies. Once a response has been established, it is unlikely that repeat boosting will be able to change its scope, meaning that balanced responses against the four virus serotypes will need to be established with the first vaccine dose."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014204

your link only reports on primary and secondary dengue. There is no analysis of how long of a gap there was between primary and secondary, and whether that length of time matters. I don't see any evidence whatsoever in that link of a "long-lasting" original antigenic sin.

From the paper I originally linked: "Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three." Dengue researchers routinely talk about lifelong original antigenic sin effects in dengue. You seem to want to split hairs and ask instead "but which papers specifically established the duration of the original antigenic sin in dengue". I can't help you with that beyond linking to the seminal Halstead 1983 paper. From there on you are on your own.

https://pubmed.ncbi.nlm.nih.gov/6824120/

I'm not splitting hairs at all. The point that infection with one serotype elicits lifelong immunity to that serotype only, is not original antigenic sin (OAS) at all, much less lifelong OAS. To make sure we are discussing the same thing, OAS (to me) refers to the effect that infection with (or vaccination against) one serotype makes it difficult/impossible to obtain any useful immunity to a second serotype. Lifelong, means that this effect is very long-lasting (years). If dengue researchers routinely talk about such, then you should be able to produce one paper that demonstrates it. Certainly Halstead does not although it contains an interesting reference to and discussion of the earlier work by Eisen, suggesting OAS lasting 7 months in rabbits. However, my larger point is this: a strong enough OAS effect to actually blunt vaccine effectiveness is rare. In fact, other than Dengue and RSV, have we really every seen proof of it at all, never mind whether it is long-lasting? For example, Influenza vaccines infections do show a slight OAS effect, but vaccination still works very well.

There are other studies suggesting that infection + two doses of Pfizer could be effective whereas just two doses aren’t.

Would you have preferred to have a 103F fever for 2 weeks, your stamina be shot for almost a year, and a bunch of auxiliary symptoms?

Speaking as someone who got Covid Original Flavour(tm) before vaccines, I'd gladly trade our positions. And my case would be considered "mild"--I never lost my sense of smell, for example.

I've been following the research closely and haven't seen this anywhere. Mind linking to the studies?

Discussion on HN of the Moderna vaccine released to GitHub. https://news.ycombinator.com/item?id=26628233

Moderna targets one specific feature of one variant of the virus. If the virus evolves to minimize this structural feature, then this mitigation will fail.

It's a functional feature.

> This is consistent with other research showing that people who are vaccinated then infected are more likely to get reinfected

A study that showed this was what I was looking for.

"Well the problem suggested by other research is that when vaccinated people are infected with a functionally different strain they don’t appear to create new antibodies."

Do you refer to the mRNA vaccinations only, or vector vaccine, too? How about the inactivated type vaccines? Simple logic says, you would be better off with those?

It's because there are two main types of studies getting published: studies based on the actual virus or real world observations, and studies based on a pseudo-virus or simplified modeling.

This study is the latter- it only tests efficacy against the spike itself, and nothing else.

The study that suggested natural immunity plus the vaccine is the best protection was similarly based only on the spike protein.

So any immune response based on any part other than the spike gets neglected, and I suspect that's at least somewhat intentional.

I briefly skimmed the article at the medrxiv link, but it does not seem to assay neutralizing antibody titer. Rather the medrxiv link just assays "reactivity." I suppose it would be great if the booster increased reactivity against all variants. But it is not so surprising that a booster furthers the selection of higher affinity antibodies, which tend to be more specifically adapted to the antigen. However, at the end of the day, the Pfizer data shows that either this decrease in reactivity is not enough to overcome the recovery in titer elicited by the booster or that the decrease in reactivity is not a general phenomenon. Or, hopefully not the case, we will start to see this decrease in reactivity effect as we look at larger sample sizes. I think there is a ton of data available to Pfizer about booster titers/effectiveness, so I would be surprised to see larger sample sizes change the conclusions.

The real question is how this translates to actual protection against serious disease. These increased responses sound impressive but, beyond some threshold, additional response offers only negligibly better protection.

Do we know what those thresholds are?

No, at least to Christian Drosten [1], he explained multiple times in his podcast, that it is quite hard to compare antibody titers from different laboratories and therefore it is hard to define general safe thresholds.

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

BioNTech distributes directly in Germany for sure. Also as far as I know in all European Union countries, because they basically bulk-ordered their vaccine supply together (though the deliveries are individually split up to each country).

But in the end it shouldn't matter anyway from a financial perspective, since BioNTech and Pfizer have a 50:50 split agreement on all costs and revenues related to the vaccine. That agreement should nullify any possible influence of distribution region assignments on the financial results.

Is it possible to officially buy a BioNTech dose in Germany ?

Yes and no. You can order Comirnaty in Germany if you're a doctor's practice, and the deliveries will come from the central distribution facilities in each German state. Those facilities are receiving shipments from the Marburg production facility that BioNTech owns and operates. Similarly, if you were to do the same as a Belgian physician, you would receive shipments that originate in Pfizer's production facility in Belgium. It's exactly the same product though. I don't know if there's a difference in the labeling beyond specifying production site. The production lot labels you get for each dose to be added to patient vaccination records look exactly the same (other than the lot serial numbers of course).

However doctors cannot currently order Comirnaty "directly" from anywhere except from the government-controlled distribution system, which operates along the same basic distribution lines that are also used for other vaccines and medicine products, but is governed by special rules (for example the government can limit the number of doses a single doctor can order if demand outstrips supply).

And when it comes to ordering from the manufacturer, whether it's Pfizer or BioNTech, AFAIK nobody except nation states can do that. They just don't accept anyone else as customers - with very rare, but notable exceptions (there was this occurrence where the company TSMC ordered some millions of doses of Comirnaty as a proxy for the Taiwan government because some weird Chinese intervention, of which I didn't fully understand the exact mechanism how it worked, prevented Taiwan from ordering directly).

> Does anyone have a list where BionTech distributes directly?

It's Germany and Turkey.

In a press release earlier this year[0], BioNTech described their relationship with Pfizer and they listed the countries it covers. Also, for China they have another company instead of Pfizer.

Why Germany and Turkey, you may ask? Well, the inventors and founders of the company are Turkish immigrants to Germany. So they are able to give the vaccine on special terms to the country they came from and the country that made them. To be honest, Turkey is extremely lucky that they feel like helping out the motherland. Thanks to them, Turkey has abundance of the vaccine and probably at a good price.

[0] https://investors.biontech.de/news-releases/news-release-det...

They also have a licensee (and early R&D investor) in China, Fosun Pharma. I don't know if Fosun is actively manufacturing and distributing, but I think they have the exclusive rights for the Chinese mainland, Hong Kong, Taiwan and Macau.

Doses of BioNTech vaccine distributed by gov'ts in Hongkong and Macao were manufactored by Fosun Pharma. As vaccination rate has dropped dramatically since the initial rush, I don't know if Fosun Pharma is still manufacturing the BioNTech vaccine. Weirdly, I still don't think any foreign made vaccines are approved in mainland China.

Wiki: https://en.wikipedia.org/wiki/Fosun_Pharma#COVID-19

I cannot find any references via Google that prove Fosun Pharma has exclusive rights for Taiwan. If anyone has any specifics, please reply. Honestly, I doubt it, as Fosun in a mainland Chinese corporation and China was actively blocking Taiwan out of international COVID efforts efforts vis-a-vis WHO (World Health Org).

> "Fosun Pharma has been licensed by BioNTech to exclusively develop and commercialize COVID-19 vaccines based on its mRNA technology platform in Chinese Mainland, Hong Kong SAR, Macau SAR and Taiwan region."

https://investors.biontech.de/news-releases/news-release-det... (2020)

Searching the CDC in Taiwan, I was unable to find any press releases announcing they bought vaccines from Fosun Pharma. Everything I could find said they only received BioNTech vaccines when they were donated. Please correct me if wrong. I assume "Taiwan region" is simply something to satisfy the PRC gov't (CCP) which believes Taiwan is a part of its country and governed by PRC.

TW CDC PR: https://www.cdc.gov.tw/En/Bulletin/List/7tUXjTBf6paRvrhEl-mr...

Just like you I don't take statements like this at face value due to the complexities involved. :-)

My understanding is that folks locally didn't trust the Fosun-made batches, but Taiwan couldn't purchase vaccines from Pfizer due to Fosun holding the distribution rights

Hence the donations

There are no Fosun-made batches.

I tried to Google about this issue, but I couldn't find anything. Can you suggest a link or a Google search? I would appreciate to read more about this issue.

>I assume "Taiwan region" is simply something to satisfy the PRC gov't (CCP) which believes Taiwan is a part of its country and governed by PRC.

To be fair, Taiwan (Officially the Republic of China) also claims that it is a part of China and is in fact the rightful rulers of China. The Kuomintang withdrew to Taiwan after losing control of mainland China to Mao and the Communists. I'm not super up to date on the latest claims between China and Taiwan, but Taiwan has never recognized officially that they do not rightfully control China.

That is not true. All BioNTech doses used in Hong Kong were manufactured by Baxter in Germany for BioNTech and then distributed in HK by Fosun.

Latest: https://www.info.gov.hk/gia/general/202110/16/P2021101600482...

(they keep falsely claiming Baxter to be a city in Germany. It's a company that manufactures for BioNTech, not a city. https://www.baxter.com/)

Outstanding. Thank you to correct me! It is so weird that a mainland Chinese company is "arranging" delivery of a vaccine from Baxter (a German company) to Hongkong that is not approved by mainland China. Simply bizarre.

I found more: https://www.covidvaccine.gov.hk/en/faq

<< Quality

60. Where is the Comirnaty vaccine supplied to Hong Kong produced? How to ensure the quality of vaccines supplied to Hong Kong?

According to the information provided by Fosun Pharma, the Comirnaty vaccines for Hong Kong will be produced in Germany. Click here to read the package insert.

The vaccine manufacturer must comply with the Pharmaceutical Inspection Co-operation Scheme (PIC/S) Good Manufacturing Practice (GMP) standards, or equivalent. The imported vaccine also has a Certificate of Analysis to prove that it meets the specifications. >>

You wrote: <<the inventors and founders of the company are Turkish immigrants to Germany.>>

I double checked on Wiki. There are two founders -- husband and wife. While both have Turkish heritage, only one is a Turkish immigrant. To be fair, I agree with the overall sentiment of your comment!

Husband: Uğur Şahin was born in Turkey, and immigrated to Germany at age 4

Wife: Özlem Türeci was born in Germany. Her parents immigrated to Germany from Turkey.

If anyone is interested to learn more about these amazing scientists, I recommend that you watch the YouTube video where they are interviewed by CEO Mathias Döpfner for one hour after winning the Axel Springer Award in 2021: https://www.youtube.com/watch?v=B4u4JzAZQoc

They are part of the Turkish diaspora in Germany. Wouldn’t know about the exact birth details but they played substantial role in the vaccination program in Turkey.

They also wrote a book

Nice tip! I didn't know about it. I found this: https://us.macmillan.com/books/9781250280374

<< The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic

Author: Joe Miller with Dr. Özlem Türeci and Dr. Ugur Sahin >>

Interestingly both last names are written incorrectly on the cover (should have been TÜRECİ and ŞAHİN -- with a dotted capital I). Looks like a bug in the "convert to all caps" function of their publishing or design software. It can't be a font issue as they were able to print "Ğ".

You can say one is 1st generation immigrant, and other is 2nd gen: https://en.wikipedia.org/wiki/Immigrant_generations

Sorry, but I need to push back against this sentiment. Where is the limit? It strikes me as exclusionary, and many other young, educated Germans have agreed with me on this specific point. When I lived in California, I met Chinese Americans who had lived in the United States longer than my family (1850s, 5+ generations). With a purely reductionist view, does everyone remain an immigrant in the United States ad infinitum except Native Americans? Is that also true in Malaysia, Canada, Peru, Taiwan, Brazil, New Zealand, Fiji, and Australia from their/your cultural view? It strikes me as "Ad Absurdum". To really stir the pot: Considering the recent Black Lives Matter movement, are all African descent people absolutely and continuously for all eternity "immigrants" where ever they live away from the African continent? Repeat for the descendents of the Indian subcontinent, whom form one of the largest diasporas in human history. I have watched and read multiple interviews with Özlem Türeci, and, each time, she specifically pushes back against this posturing: "Oh, but you are 'truly' Turkish."

This is the meat in the meat...

> Neutralization against the Omicron variant after three doses of the Pfizer-BioNTech COVID-19 vaccine was comparable to the neutralization against the wild-type strain observed in sera from individuals who received two doses

This means that the vaccine is still effective - but very clearly LESS effective than it was against earlier variants.

We need UPDATED booster shots each year. The new normal will be boosters every year as we have with the flu.

Is there any evidence for covid reinfection?

Returning to this one after doing more research, there seems to be a 90%+ protection after reinfection, from all strains so far, and similar protection against hospitalization. Vaccination effects on previously infected individuals is touted as giving better protection, but the data is shaky at best. We'll need years more data.

Those who wants booster shots can take them, while those who don't want to are free to do just that.

Same as with the flu, which of course means that we do away with Corona passport and the other limits we set up.

The end goal is to treat Corona exactly the same way we treat the flu, ie. your personal choice will not lead to restrictions.

If I'm reading this correctly, this is "protection against severe disease" and has little to do with transmission. The National Airport Data from Israel seems to suggest "the absolute number of infected individuals in the Vaccinated (boosted) group is likely to be at least as high as in the Unvaccinated" [0]

So it seems to me that as long as we all remain obsessed with case numbers and not actual hospitalizations and death, this isn't going away, at least not anytime soon. I personally find this beyond depressing.

[0] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3963606

> all remain obsessed with case numbers and not actual hospitalizations and death

It's a balance. E.g. Germanys current trouble is a direct consequence of official policy that had a core of "we only care about hospitalizations now", but ignored "... and based on case numbers and other statistics, what will future hospitalizations look like if we don't change anything about our approach" - not helped by election campaigns and politicians publicly admitting they haven't understood this whole "exponential" malarky yet. You really need to consider more than just one number.

The superseded government (by way of Jens Spahn) admitted that it held back on acting w.r.t. COVID in 2021 to avoid negative impact on their campaign. General inaction or adverse action in other areas (e.g. ICU staffing, leerdenker) did not help, either.

As someone who has quite some experience in running operations based on data, numbers and metrics the German approach to COVID on that front alone really puzzled me from the beginning. First the incidence of 50 that they pulled out of their ass for contact tracing, which was ignored basically the next day. Then the fact that resources weren't really increased to improve contract traceability. Then the decision to use a backward looking KPI, ICU occupation, to tackle a highly dynamic situation. Which also meant to ignore the incidence, the only real predictive metric we have. And it is good at predicting ICU occupation and severe cases when combined with vaccination levels.

That's simply amateurish, and means all measures, not all of which are bad, are usually a couple of weeks late. Even better, the 7-day average incidence is based on the daily numbers. Those numbers are, what a surprise, limited to the testing capacities of laboratories, so the incidence is reported based on the day the test was analyzed, not when the sample was taken. This flattens the 7-day average curve. Well, until the new numbers are reported once labs git through their backlog. Thing is, the 7-day average is not changed once published. Again just amateurish.

Yes, it's been really frustrating to see RKI predict this for weeks and just ... nothing happening. And then you still get headlines of "incidence fell slightly!" - from 392,4 to 392,2 (or sth like that), when testing labs are hitting capacity. We somehow lucked into a relatively good first wave and ever since then... so much unnecessary mess.

The drop in incidence is the same BS when reporting in DAX or S&P moving by 0.2 % day-to-day. That's noice, no signal.

EDIT: That's also noise for HF traders, because day-to-day numbers are pointless when you worry about milliseconds.

German government staff is as un-digital as you can get. They have no idea how a small modeling group would have helped. Maybe the incoming government will do better, but I am not holding my breath.

Access to modeling isn't even the issue, given RKI, Charité, ... Asking those resources the right questions and turning their results into policy and communicating it is the problem, which is even more fundamental "that's what a government is for" skills...

Being digital doesn't necessarily improve decision make. All the necessary data was there. RKI the German equivalent to the CDC in the US predicted the current wave rather accurately in summer, but politicians ignored it, because they wanted to win the election.

It's not modelling, just having a basic understanding of your metrics and the ability to choose the right ones. German officials showed none of that. Well, I'm not holding my breath on that neither.

It tells you a lot of the level of expertise in a country, if a physicist like Viola Priesemann previously not involved in any kind of disease modelling is able to be a significant voice in the national conversation. The 'experts' that are listened to are either numerically illiterate like Drosten or non-experts in disease control like Priesemann. Moreover the actual tools and quality of code that is used to model the situation are so far away from what would be ideal it is laughable.

You really think Drosten and Priesemann decide measures? That's politicians, the government decided on it. If I remember well, scientists were worried when hospitalization was declared the only truth.

And the RKI predicted the forth basically down to a T, they were a couple of weeks of so. Doesn't matter because they predicted, along with Drosten, already during summer.

I think there is an expert vacuum that was filled by opportunists and enabled politicians to decide non-sensical measures. Compare that to the situation in Taiwan, where the vice-prime Minister is an epidemiologist.

Also the "honor system" for quarantine. Also the closure of museums (airy, 25% capacity, everyone masked) but not department stores (crowded, many ignoring mask rules). Also the fact that my art-supply store in Berlin had to cordon off the half of its inventory that wasn't on the "essential" list, so some paint yes, some paint no. Also the refusal to confront the anti-vaxxers (police complicity, etc). Also the very public promises they knew they probably couldn't keep (Christmas is big in Germany).

I had a pretty high opinion of German government competence, Berlin-specific dramas notwithstanding, before the pandemic. I now have a very, very low one.

Yes an authoritarian police state enforcing quarantine in Germany sounds like a great idea. I'm sure there are historical examples they can follow.

Or, you could be honest with the public and call it voluntary.

In many countries, compulsory quarantine was enforced. In Germany it never was, but they still presented it as compulsory and held out the possibility that it might be enforced.

I don’t wish they had enforced it, I wish they had been honest about the arrangement.

Well, this is the issue you have with a lot of these lockdown, mask laws. Are they enforceable? No, unless you have a compliant population and in that case no law is probably necessary.

Almost all western governments did a piss poor job of preventing facts which why we're in the situation we are now. They appear untrustworthy because they've presented partial truths or completely changed their stance throughout.

"Remain obsessed" with transmission of a highly contagious virus that has shown significant ability to mutate at scale? That sure seems worth being obsessed about. When it mutates to spread past all current defenses then consistently kill because we failed to stop current spread it will indeed be "depressing".

There is absolutely no way to stop the spread forever. Just suggesting it is crazy. It is an option you have to forget about.

Stalling the spread is useless as well - we have already had two major mutations in less than two years.

>we have already had two major mutations in less than two years.

How frequently do equivalent Flu mutations occur?

Every. Single. Year.

> There is absolutely no way to stop the spread forever.

Well, there is, we just don't want to pay for it: vaccinating poor countries, where effectively the mutations are being created by high infection rates.

The vaccine hasn't stopped spread in rich countries, why would it do so in poor countries?

Also there haven't been enough variants as to determine that most variants are coming from poor countries. Speaking of delta, India has more population than the entirety of Europe. Mathematically it makes sense than a variant could come from there regardless of whether the vaccine does anything.

> The vaccine hasn't stopped spread in rich countries, why would it do so in poor countries?

It has greatly slowed the spread. The highest vaccinated countries have almost stopped it. There is every reason to believe that high vaccination across the world would stop covid, and anything less will ensure continued spread (and mutations).

People demanding an all or nothing from a vaccine are missing the big picture.

The highest vaccinated countries have almost stopped it? Israel had among the highest vaccination rates in the world prior to its most recent peak, which has now declined. Other countries are going through the same thing. There is only a very rough/weak correlation between vaccination rate and positive cases.

Isreal hasn't been among the highest vaccinated countries in quite a while. They got over 50% early, but stalled out. https://ourworldindata.org/covid-vaccinations (Isreal isn't selected by default) Check out countries like Portugal if you want to see what high vaccination does.

It is depressing how people pretend that it is the same virus every time.

Israel has faced waves of 3 different viruses - original, Alpha and Delta what have required different level of immunization and Israel has managed to vaccinate itself out of 2 of these waves.

Looks quite impressive to me.

I also fail to understand why people pretend that 2 doses should be expected to stop Delta that has higher viral load - it does not make any sense.

It is a probabilistic game - antibodies are not smart - they are like mines - you need to have high enough concentration to stop viral particles to move around. If the viral particles can overload this concentration - they are going to win. There obviously must be some threshold of antibody concentration below what you can't avoid infection - when 2 dose regimen reaches it too quickly, well, game over. 3rd dose regimen is known to boost antibody concentration and keep it high for longer time. There is no surprise here and yet even people in position (like WHO) that should know better have intentionally ignored it.

Don't forget to vaccinate the wild deer and other animals that catch and spread COVID.

I don't understand: every single study out there says that vaccinated people do still catch the virus and can still spread it.

Why would the current crop of vaccines be able to stop the virus, even if applied worldwide, seen that they don't prevent infection?

If the vaccine brings R0 down to below 1.0 for vaccinated people, then the vaccine offers a way to get the virus to an endemic situation rather than a pandemic.

The evidence is still not solid on whether or not it does this, as far as I am aware.

> There is absolutely no way to stop the spread forever.

There's a significant difference between COVID-19/SARS-COV-2 become endemic, and it continuing as a pandemic that threatens public health systems due to caseload density. Yes, we're unlikely to get beyond it being endemic, which means that like influenza, it will continue to be an issue, but we can certainly get a point where it is "just endemic", which would be a huge improvement over the current situation.

If you ignore the context and the multifaceted consequences of lockdowns etc., then yes, you are correct and we should be obsessed with the transmission rates. However, we don't have the same level of obsessions about other viruses present in humans (say, HSV-1 which unlike SARS-CoV-2 will live inside you until you die), and even other coronaviruses. Why? Because what matters most is how dangerous the virus is.

Fortunately, as of today, Omicron deaths are still at zero, and this fills me with moderate optimism. [0]

[0] https://www.cityam.com/anxiously-optimistic-south-africa-hol...

> Omicron deaths are still at zero

Omicron hasn't been around long enough to expect many deaths yet. Even the optimists need to wait a few more weeks.

Plenty of evidence that Omicron has been around for a substantial period of time. I believe the lower bound is at least a month in the US and Europe at this point, presumably longer at the point of origin.

technically you are right. However delta is dominate and we don't sequence most tests so we don't really have any data to work with.

sewage treatment testing happens behind the scenes, involves essentially the entire population, and is incredibly valuable. it confirms omicron's "long term" presence in the US.

"a highly contagious virus that has shown significant ability to mutate at scale"

That doesn't uniquely describe COVID. It describes pretty much every virus you have heard of.

The gradient for viruses trends strongly towards trading severity for contagiousness. They do not generally "mutate past all defenses and kill", the generally "mutate past defenses and give slight to non-existent symptoms", for several reasons, the two most important of which is that killing means they can't spread anymore, and at the Pareto frontier (which viruses live on all the time), contagiousness and severity are in active conflict with each other; energy put into one comes right out of the budget for the other. And viruses have no particular interests in making you ill... they want to spread.

You've been amped up to a level of fear so severe for viruses that if your fear was accurate, there would be no multicellular life on Earth, because highly contagious and severe viruses would kill anything that provided such a big target. So, good news! Your fear is not accurate. You can verify yourself by checking your environment for multicellular organisms that have not been killed by viruses.

This theory of "killing means they can't spread anymore" doesn't really work out with diseases like sars-cov2. It might have worked in a medieval world where people travel by foot, horseback or sailboat, and with a disease where the carrier stays contagious forever.

But we are in a modern world where travel around the globe happens in 24 hours. Covid is contagious for some time before the patient has any symptoms, and for most people, it stops being contagious by the time some of the carriers are so sick they might die.

So, when a patient starts having symptoms in 5 days, (s)he may have had time to infect other people on more than two continents.

A virus that kills the patient will still infect less people than one that doesn't.

The fact that viruses in general can spread more widely and more qiuckly doesn't change this.

> And viruses have no particular interests in making you ill... they want to spread.

To restate this without the teleological angle: virus will not become widespread unless they are easily transmitted, and they are not easily transmitted if they make the subject excessively ill. Ergo, the most common viruses are better at being transmitted than making people really ill.

I seriously question whether we're at a level technologically that "control" was ever an option here.

With things like covid and the flu, vaccines will always be playing catch up with variants. Its not like the measles which doesn't mutate. Infection and hospitalization rates for vaccinated with covid are already significantly higher than the flu as far as baselines go .. it's reasonable to say we can't expect vaccines to snuff out this kind of disease.

Therefore, the only realistic way to stop the spread is with ruthless targeted testing, tracking, and quarantining. But the problem with that method is by the time we're aware of a problematic strain, its already spread too much for quarantining to be effective.

Nature is inevitable. Once we've done all we can, all that's left is to learn to live with it.

That’s a weird way to phrase your second paragraph, considering hospitals have been close to full very recently in parts of the us.

https://protect-public.hhs.gov/pages/hospital-utilization

Sure, but I'm willing to bet most of the hospitalised are not vaccinated, or at least a disproportionate amount of them aren't vaccinated

How much are you willing to bet? Keep in mind that if the population is 90% vaccinated, you expect something approaching 90% of ICU beds to be vaccinated (well, with an effective and sterilizing vaccine you wouldn’t expect this, but that’s not where we are).

In England last month, 79% of Covid deaths were vaccinated. Currently about 36% of hospitalizations are unvaccinated.

The raw data is here, good luck parsing anything useful out of it: https://assets.publishing.service.gov.uk/government/uploads/...

A majority of deaths in the winter months will be elderly people with underlying health conditions that might have died from a flue or cold virus if covid was not circulating. It's more interesting to see excess deaths for this winter. I have a hunch excess death rates will be similar to 2019.

I don't think so, but we can quite well follow it up here, for most developed and semi-developed countries.

https://ourworldindata.org/explorers/coronavirus-data-explor...

(As OWID relies on official data sources, they may be skewed or manipulated for undeveloped or autocratic countries)

Not really. With population vaccination rate nearly 90 % we have something approaching 30-40 % of hospital and ICU bed users vaccinated.

The risk of ending up on ICU is about 30 x higher here, when comparing similar demographics. Risk of needing to go to hospital is 19 x higher currently.

The UK is interesting in that only about 70% of the population is fully vaccinated, which seems to be less than the proportion of Covid-releated deaths that were fully vaccinated. This isn't because the Covid vaccines are ineffective at preventing death - it's just that age has a much bigger effect than vaccination on someone's risk of dying from Covid, and the high-risk age groups are almost 100% vaccinated whereas the lowest risk are largely unvaccinated.

Yes, and generally the age risk is so high that proper assessments must be done comparing age cohorts, not the entire population vax/unvax rates.

I've been trying to get a clear answer to this for some time, because at least in Switzerland, and apparently in other countries as well, vaccination status of hospitalizations and deaths is well published, while vaccination status of ICU occupants is reported only anecdotally.

As you say, a sizable percentage of deaths (~50% in the 60+ age group) are vaccinated — because those tend to skew elderly (85 in Switzerland) and highly vaccinated (>90%).

Likewise, a sizable percentage of hospitalizations (~40% in 60+) are vaccinated — those are a bit younger (66 in Switzerland) because many of the very elderly patients never make it to a hospital.

All the ICU administrators I've seen interviewed, however, say that their ICU occupants are ~90% unvaccinated. One explanation for this might be that the ICU median age is considerably younger than the above ages, about 55 in Switzerland, and younger population groups are less vaccinated.

But IF this is in fact the case, I wish the statistics were public.

Hospital beds were "maxed out" before the pandemic. [0] at around 64%. They are sitting at around 78% on average now, with hard hit areas at around 80-85% according to your link. These are almost all at-risk and unvaccinated people. That's my point. If mandates and lockdowns are based on case counts instead of actual dire outcomes, then I fear we're going to continue seeing strange policies and laws for people at little to no risk, namely children and the vaccinated.

[0] https://www.webmd.com/lung/news/20200326/us-hospital-beds-we...

Apparently there was a flu epidemic during 2017-2018 and hospitals were being overwhelmed by flu patients [1].

[1] https://time.com/5107984/hospitals-handling-burden-flu-patie...

2017-2018 was an unusually deadly flu season:

> More than 80,000 Americans died of the flu in the winter of 2017-2018, the highest number in over a decade, federal health officials said last week. Although 90 percent of those deaths were in people over age 65, the flu also killed 180 young children and teenagers, more than in any other year since the Centers for Disease Control and Prevention began using its current surveillance methods.

https://www.nytimes.com/2018/10/01/health/flu-deaths-vaccine...

Other contemporaneous reporting:

https://www.nytimes.com/2018/01/26/health/flu-rates-deaths.h...

https://www.nytimes.com/2018/02/02/health/flu-symptoms-virus...

Meanwhile:

> Overall, more than 771,000 COVID-19 deaths have been reported in the U.S. during the pandemic. About 385,000 were reported in 2020, according to CDC data, and more than 386,000 have been reported this year.

https://www.webmd.com/lung/news/20211122/us-covid-deaths-202...

So 2021 alone has nearly 5x the Covid19 deaths as the 2017-2018 flu season. Also:

> As of last Monday, nine hospitals in Michigan were 100 percent full (https://www.michigan.gov/coronavirus/0,9753,7-406-98159-5236...), and at least 20 others were at or above 90 percent capacity. Statewide, nearly one in four hospital patients (https://www.bridgemi.com/michigan-health-watch/michigan-hosp...) has a confirmed or suspected case of Covid-19. In the last few weeks, my hospital has been consistently at or near capacity and nearly every day the vast majority of those patients are sick with Covid-19. Nearly all have been unvaccinated.

> On some shifts, the stress in the air is palpable. My colleagues and I know the patients are piling up, but there just are not enough nurses to properly triage everyone. A patient experiencing heart failure waits in an emergency room because inpatient rooms upstairs are all occupied. Patients who need surgery can’t be transferred because nearly every hospital within a two-hour drive is near or at capacity, too.

https://www.nytimes.com/2021/12/08/opinion/covid-michigan-su...

Hospitals are not designed to be empty, though. So you can’t just point to 80% full ICU beds and say a hospital is overwhelmed. Is there any data showing ICU beds filled above carrying capacity? Or number of patients transferred to a different hospital due to bed shortage?

This is the reported situation here in Minnesota as of yesterday: “Statewide, nearly 98% of adult ICU beds and 95% of overflow, observation, and active surge/expansion beds for adults were occupied, according to the state Department of Health.”

Likewise, hospital are routinely denying transfers. I’m also not sure what “above carrying capacity” would mean here. They’re not sticking two to a bed.

Even in countries with fairly good covid situation (I'm in Finland) we are going to see excess mortality over the coming years, because right now as we speak, elective operations for heart surgeries and cancer operations are being postponed in order to make room for covid patients.

ICU wards are designed for normal operations at near-full capacity. Maintaining a large-scale vacant ICU capacity is both uneconomical and operationally very difficult (because ICU treatment skills are highly specific and learning, maintaining and updating them requires one to be working on the area).

This will show up as excess mortality of "preventable deaths".

But those stats will be overshadowed by 2 larger factors:

1. the pendulum will swing back as covid goes to zero .. fewer unhealthy and elderly members of the population will result in overall lower mortality rates in the short term (2-3 years).

2. baby boomers are coming of age .. a baby boom is eventually followed by a death boom. This will drive up the mortality rate long term (5-10 years).

In Germany wr have evacuatiom flights from Bavaria to Hamburg for example. We had that early in the pandemic from France and Italy to Germany. So yes, there are numbers for sure somewhere.

This is neither about transmission nor severe disease. The study itself is a lab test to see how the new virus holds up against the vaccines, their suggestions about protection are still conjecture

Yes, as far as I understand it's somewhat of an indicator for infection risk, but can't capture overall consequences, and I think right now any strong statement for "it's going to be this bad/not bad" should be taken with a large grain of salt - we just don't know yet and are watching datapoints coming in day by day.

The reason why people are obsessed with case numbers and not deaths is that case numbers control the case numbers in the insufficiently immunized which predicts death toll 3 weeks ahead of time.

Why would you want to control a system with 2-3 weeks of additional lag in your input data when case numbers (a thing that is somewhat easy to measure) correlates so well future deaths?

Ideally politician would have some family of models the equivalent of the CDC runs 3 weeks into the future which accounts for seasonality, social events so we could model predictive control on the death numbers but my impression is that is not done (transparently), due to mistrust in experts.

That’s not necessarily true. If you suddenly start testing low risk people you weren’t testing before, then you can get an increase in cases without necessarily an increase in death.

For example, if you implement a travel rule that every traveler needs to get tested a day before they leave and a day after they arrive, then you’re going to see an increase in cases (both real and false positives).

Yeah, but in practice that hasn’t been relevant.

It’s important to be cautious, but it’s also important to not be a know-it-all who just because they can think of a limitation of a data collection / statistical method they can suddenly cast doubt on the whole thing, even though people who know much more about it already probably did exactly the same thing.

Finden a limitation of some data is extremely easy. Extremely easy. It will literally always be possible whenever people are working with data about people because this shit is hard. That doesn’t mean you get to name that limitation, cast doubt on something and piss off. That’s unproductive and irresponsible.

These are the facts: incidence is a great leading indicator if some care is taken with it and it’s regularly put into the larger context (i.e. given more vaccinations a higher incidence is possible until things turn to shit). And you can shout data limitations at that central fact until you are blue in the face but it’s still gonna be there and true.

For a successful technology(/medical intervention), reality must take precedence over public relations, for nature cannot be fooled

All of that plus "What kills people from COVID now?" To which the answer is "Lack of access to ICU-capable health facilities."

And what causes lack of access? Total number of people hospitalized. And how does that number grow? Exponentially.

So every public health department in the world is optimizing for "How do we prevent our limited number of ICU-capable health facilities from being overwhelmed."

And that comes down to predicting the future hospitalization rate, which can be predicted by the current case count as you said.

I agree completely, with the addition that this has been the case pretty much from the start. Evolution of therapies has been minimal, the killer factor has always been the level of pressure on health services - which doesn't just mean ventilators as initially thought, but the entire care process over several days. And this is why vaccines are a game changer: they remove the need for hospitalization.

Also, obligatory: staff. Which is to say the health care system is sized for employing enough highly-trained trauma / ICU staff to support normal operations, with some small (very small) amount of surge capacity. And people under-estimate the specialization & experience required for high-level ICU and respiratory care. You can't just take a floor nurse and transfer them over to do the new work.

And the amount of complex hospitalizations due to COVID can very quickly become a couple orders of magnitude above "normal operations."

' "What kills people from COVID now?" To which the answer is '

Matching with observed reality a better answer may be: 18 months of enhancing the comorbidities of being overweight and in poor physical condition. Sitting on couch while snacking on carbohydrates and fear has been detrimental to many people.

> Why would you want to control a system with 2-3 weeks of additional lag in your input data when case numbers (a thing that is somewhat easy to measure) correlates so well future deaths?

Because case numbers are actually not easy to measure.

I'm basing this of my personal experience working in a German healthcare company, we took up testing during the pandemic; All the tests we do are on unvaccinated people.

That's because unvaccinated people are the only ones who need mandatory, and up to date, tests for pretty much everything from the barber to eating at a restaurant. Recently, it's become so strict that unvaccinated people even need a test to use public transport.

Vaccinated people do not need these mandatory tests, I have no clue who tests them and at what intervals, it certainly ain't the public testing stations, as those are now literally swarmed by the unvaccinated and nobody would go there if they didn't have to.

Which means that in practice we have a massive sampling bias going on; Somebody who's unvaccinated will be very likely to get flagged as positive very quickly, while somebody who's vaccinated would need to decide on their own to do a test.

The obvious solution to this problem is to do actual random sampling: pick members of the public in as close to a random fashion as possible, test them for Covid regardless of vaccination status or symptoms, and you should be able to get a reasonably unbiased estimate of actual infection levels in the community. The UK has been doing this since about spring 2020, but weirdly no-one else seems to even though it's obviously useful.

Just doing random sampling on a small group to estimate the error ratio should also work. Also as long as everyone who has symptoms can get a test the error ratio is bounded by the ratio of people with symptoms making it irrelevant for this control problem.

Better is the worst enemy of good. Please suggest a different metric then. One that can be measured easily and will do about as well as the biased infected numbers or one which will do better than the biased infected numbers at a similar effort.

There is little control theoretic relevance of the Dunkelziffer smoothly varying between 2 and 6 as long as that doesn't make the controller overlook a wave (it doesn't). The sign of the policy should still be the same and if measures don't work, harder measures are imposed means we basically got a PI(D) controller and can achieve stationary solutions even if the Dunkelziffer changes smoothly.

Sure, there is selection bias. Given the overall effectivness of vaccines, the number of positive, yet untested, vaccinated people should be rather small. Plus, those vaccinated without symptoms most likely are not the problem as they are not really infectious. Once you develop symptoms you are tested.

On tip of that, a lot of states are now on 2G+, recovered or vaccinated and tested (anti-gen), for things like cinemas (requiring official tests in e.g. Bavaria) or self tests on site (fitness studios for example). Kids are regularly tested in school (my son three times, my daughter twice). Sure, some of those tests, those at fitness studios, are not counted. If those are positive, I think the number of people not getting a proper PCR test is rather small.

I'm sure you're right regarding sampling bias, but the vaccinated people I know have not turned off their phone contact tracing alerts, and get tested if they receive a tracing notice.

People get tracing alerts? I've had the apps of three different countries now for some 1.5 years running now and never received even a single blip.

Maybe, maybe not. It is clear, even to someone with zero background in vaccines, that the COVID vaccines are no resulting in sterilizing immunity. Everyone said as much since the first trials.

What does this mean? IMHO it means that once we reached sufficient levels of vaccinations (no idea what that would be, definitely above 70%) COVID will be nothing more than a severe flue / cold for most of the population, if they get it at all. It would also, I would assume, push mutations down the more infections and less severe route in order to overcome the limited spread among the vaccinated (they are still overall less infectious then unvaccinted people) and the vaccines themselves. Both are good news.

And that drives me so crazy with the anti-vaxxers (among a lot of things with them). They don't want the shots because a) COVID is just a flew (and simultaniously a deadly bio weapon the Chinese spread in order to win a global economic war...) and b) vaccinated people are also infectious and can get it. Well, they kind of have it backwards there, don't they? it actually will be like a cold because people are vaccinated, not before. At which point the fact that vaccinated people can also transmit COVID is not really important anymore.

It was already on the scale of a cold approximately for some 90%+ of people. This virus is mild or asymptomatic in the vast majority of cases and that has been apparent for a long time. The only possible justification for vaccines at this point is to minimize overloading of hospitals because of the contagious nature of the virus, the overall complication rate is still very low.

>anti-vaxxers (among a lot of things with them). They don't want the shots because a) COVID is just a flew (and simultaniously a deadly bio weapon the Chinese spread in order to win a global economic war...)

Maybe the problem is that people who are against covid vaccines are being a) slandered as anti-vaxxers and b) lumped in with all sorts of other conspiracists.

I am not aware of a common cold that resulted in hospitals being overloaded to the point planned surgery needed to be postponed. Severe cases maybe a rather small percentage, yet in absolute numbers they are big enough to be real problem.

Well, if I were an anti-vaxxer, why would being called one be a slander? Either I am one or not. And yes, they are conspiracy theorists, even worse they are of becoming even more radical every day.

But thanks for showing again the main problem I have with them: pure egoism. Covid wont be an issue for me (singing in the dark, lalala), so screw everyone else.

>I am not aware of a common cold that resulted in hospitals being overloaded to the point planned surgery needed to be postponed. Severe cases maybe a rather small percentage, yet in absolute numbers they are big enough to be real problem.

Which is exactly what I wrote. The problem with covid is its rate of spread, the actual complication rate per infection is very low. That's why I explicitly said the only possible justification for vaccines now is to prevent hospital overload.

>Well, if I were an anti-vaxxer, why would being called one be a slander? Either I am one or not

No, this isn't binary. Not all vaccines are created equal, and it is perfectly rational to be in support of vaccination in general but against covid vaccines. To blindly group such people with antivaxxers is disingenuous.

We're already at 70% or above for all the age groups that matter

https://data.cdc.gov/Vaccinations/COVID-19-Vaccination-and-C...

> the absolute number of infected individuals in the Vaccinated (boosted) group is likely to be at least as high as in the Unvaccinated

But if the vaccinated represent a much larger share of the population, the same absolute number represents a much smaller proportion who become infected.

In many countries where vaccination rates are very high (think of Spain, Portugal...) the infection cases have been increasing yet people in the hospital or deaths caused by/with the virus have been rather low. Attribute it to vaccines, natural immunity, a potentially weaker variant - or everything at the same time but my point is: I agree with you, at least when it comes to these highly-vaccinated countries.

I wish we would just stop looking at infection rates as it's never going to change as long as the virus exists (and continues to mutate) and/or a sterilizing vaccine of sorts shows up and people take it.

Focus on case numbers by means of PCR tests is problematic because a PCR test only measures virus RNA, not the cause of sickness or contagiousness.

If a thousand healthy people come in contact with the virus it is possible they all will have a positive PCR test while not being contagious at the same time.

The Netherlands assess the "risk level" based on hospital admissions and ICU admissions: https://coronadashboard.government.nl/over-risiconiveaus

We need to be able to predict the hospitalization rate to be prepared for surges, so tracking transmission is absolutely necessary. Perhaps after a long period of low hospitalizations (6 months, a year?) the general public can stop paying attention... but we're definitely not there yet.

It's looking like high double and triple vaccination rates can do it (like 80%+), but that's starting to look impossible in some countries.

Covid is endemic and will be with us forever. The terror threat indicator on news networks lasted many years and I suspect the attention to covid will follow a similar attention cycle unless something else major happens and dominates the news cycle. You'll need biannual boosters until then

This is a good point. Hospitalization and death are really all that matter. People will be getting sick (to lesser degrees, likely, but it will still happen) from this for generations to come. What really matters is whether or not you are sick in bed at home and missing a few days of work vs sick in the hospital, occupying emergency health resources and facing potential death.

And case numbers are the best metric we have to predict deaths and hospitalization. Together with vaccination rates, age and so on. But overall, if cases go up, hospitalization will go up a couple of weeks later. Why would we not use that to enable to us act instead of reacting once it's too late?

Exactly. Case numbers are not meaningless. They are a leading indicator. People unexpectedly showing up to hospitals is a lagging indicator of disease prevalence.

Because as new variants with lower virulence emerge, and we see more breakthrough and reinfection cases, that direct link will become less direct.

We don't lock down for the flu because the virulence of the flu is lower than covid and we consider it acceptable. At some point, we'll pass those acceptability thresholds for COVID as well.

For some people, and regions, they already have passed those thresholds, as both severity and people's acceptance of different outcomes vary.

I'm not into modelling, I would imagine that, depending on how good the vaccines work against variants, even that could be modelled quite well.

For me, the threshold when Covid becomes an acceptable fact of life is when hospitals can work normally without any measures in place. We seem to be quite far from that.

In my state, we have ~10k hospital beds. There are currently ~450 covid patients that are hospitalized and that's actually significantly higher than last week. I think a lot of places are pretty close to that situation now.

Of course, total hospital bed utilization is still over 80%, but overwhelmingly its non covid.

I agree with you about the focus on cases instead of hospitalizations. However, even in places with high levels of vaccination, so far cases does translate into stressing hospitals to the edge, followed by lockdown and other restrictions. See Alberta, Canada in September, or Austria two weeks ago and Germany now.

This doesn't end until nearly everyone is vaccinated, recovered, or dead. To paraphrase the German health minister.

Alberta delayed a few surgeries, nobody was triaged out of ICU care. Bringing on enough staff to up ICU by 50 more beds is the right goal for them.

They had to backtrack and place severe restrictions on what activities were allowed and also restrict activities of the unvaccinated. There were hospitals transfering patients out of province, as well as surgeries cancelled - which is a big harm. The hospitals likely would have reached breaking point had no action been taken.

I find it encouraging. A virus that’s endemic and doesn’t kill people who are vaccinated is not a big deal. Like yeah it would be great if we eradicated it, but this is really fine.

I watch This Week in Virology occasionally. A discussion among virology professors. Vincent Racaniello who kind of seems to run TWiV has been skeptical about boosters. His argument is that they're not needed (unless you got the J&J) because your first 2 vaccinations will protect you from serious illness. You might something akin to a nasty cold but you'll be protected from hospitalization or worse. His argument is also that we need to get the rest of the world fully vaccinated before we start looking at boosters here in the US.

Also, Pfizer is only looking at antibody responses here, not T-Cell & memory B cell responses and other parts of the immune system that were primed by vaccination.

Governments and public policy makers are being excessively cautious and slow to react to changes. Governments are beholden to public opinion*, and public opinion is slow to change.

I'm not trying to justify the actions of govts, I'm merely stating that slow reaction times are considered by many to be a feature not a bug.

As for breakthroughs a common problem with analyzing vaccinated with unvaccinated is that among the unvaccinated there will be disproportionally higher percentage of naturally immune (recovered), who are if not equal, better protected from reinfection than naive vaccinees.

Yeah I stopped looking at case numbers a long time ago. They're completely irrelevant, with the amount of hysteria going around. Hospitalization is the only thing that matters at this point (and in fact has been since the beginning).

Omicron is so infectious it may infect everyone available and die off quite rapidly.

If there is an expert in immunology here I'd really like to ask a question:

Aren't antibody titers just one measure of immunity?

Since ~everyone with just two shots get them a while ago, and people receiving the boosters are receiving them now, wouldn't we expect must higher levels of neutralizing antibodies in boosted people? I know the number of antibodies fades over time, (whether from vaccine or infection) but this doesn't mean you don't have lasting protection after this, right?

Wouldn't it therefore be a mistake/misleading to conclude something specific about a level of protection from this titer data alone?

Not the expert you were asking but one thing I know is natural immunity isn't just antibodies, which is why traditional inactivated vaccines yield more robust and long-lasting protection.

FYI, vector vaccines and mRNA vaccines also create t-cell immunity , not just antibodies. It’s not just “inactivated vaccines” that do so.

I did not know that. Thank you. Possibly in lesser quantities though? It is only related to the spike protein in the case of Covid. As I understand the natural immunity has a different fingerprint even with covid?

"natural" immunity would create antibodies and immunity that may be related to non-spike proteins of COVID-19 (I believe this depends on your own body's response and the severity of infection exactly what is generated).

The vector and mRNA vaccines only expose the spike protein (in various forms), so they don't generate immunity to other proteins of COVID-19.

> traditional inactivated vaccines yield more robust and long-lasting protection

This is wrong. The formation of memory T/B cells has nothing to do with the vaccine tech. Both create lasting T/B cell memory immunity.

The problem is that it takes a week or so for T/B immunity to kick in - so you still get sick.

Thank you. Shouldn't have said that with such certainty. But maybe perhaps having just the spike protein vs the whole virus is eliciting a different response? Again, I don't know.

There's the whole t-cell and b-cell stuff that protects from serious disease but it's much harder to test/measure so you don't get these rapid headline grabbing lab studies. T-cells as I understand it are much less likely to be thrown off by spike mutations because they react to whole genome of virus (edit: T-cells from an infection that is).

This is not my area but isn't the point of the mRNA vaccines that that virus' DNA is never introduced into your body? You only end up with a narrow transcribed slice of that DNA targeting a specific protein.

I've also never heard of your immune system targetting a genome; how is it generally gaining access to that genome when it is encapsulated?

My understanding of the spike targeting is that COVID is only so infectious because of the specific configuration of that spike protein. Change it too much, and it stops being nearly as infectious (and thus stops being COVID as we know it).

oh yeah thats a point, t-cells will only be able to react to the things that they've seen

> because they react to whole genome of virus

Why do you think that?

A genome codes for protein production. T-cells are something like a Unix grep for protein sequences (instead of character regexes) with their grep argument a memorized protein sequence to recognize in the wild.

So it's some sort of dumb luck if the entirety of proteins, specified in a genome's blueprints, would happen to have t-cells assigned to recognize all of them.

Good question. My vague understanding is that antibodies react to the external shape of the virus, the spike and so on. Whereas T-cells react to the little chunks of rna produced during multiplication of the virus, kindof the byprodyucts of a virus-factory-cell, and as such are not restricted to the 'outside' of the virus but can potentially learn about any part of the virus' genome. Hence T-cells are less likely to be thrown off by spike mutations. But my grasp on this is very vague.

From what I can remember from my immunology class, B-cells specific to a particular antibody will detect the antigen in a re-infection, start to massively clone themselves and quickly increase the specific antibody titer in the blood in response.

It doesn't make sense from an energy point of view for these to get produced in large volumes in the blood forever, so unless you're continually re-infected, the antibody titers will then drop but the memory B-cells remain, ready for a new round.

What's crucial is how fast the immune system can ramp up again in a re-infection, perhaps for COVID19 this is almost always fast enough to prevent a deadly re-infection but not fast enough to prevent any form of viral replication and shedding and this is why vaccinated still spread the virus around (and this might keep being the case with the current type of vaccines for corona viruses unless you deal out 10 billion booster doses every quarter).

So the question is complex and depends on what your goals are, and all of this has to be dumbed down in a way for consumption by the general public who just want to know "how long is my vaccine good for"... :/

Perhaps the antibody blood titer is not the only data that is relevant, but maybe it's determined that it correlates to one of the outcomes in a good enough way..

Hospitalization and death numbers are definitely directly connected to how long its been since you got your shot. So for now, it does not seem like the whole long immunity/T-B-cell thing is happening with Pfizer/Moderna/J&J at least

There is a very real per month affect, every month after your latest mRNA shot, your chances of getting seriously sick get a little bigger. After 6 months they get so big that scientists concluded its time for a booster. Now we wait and see, but so far things seem to be trending in the same direction, in Israel at least (so, no Moderna or J&J). Its not that we are only measuring titers. Its that vaccinated people are suddenly dying. So there seems to be no or very low memory to making more titers

Then, people get a booster, and boom, 90% lower chance of death again with high titers

https://www.nejm.org/doi/full/10.1056/NEJMoa2114228

https://www.science.org/doi/10.1126/science.abm0620

The veteran research which had 800,000 participants showed terrible long term results for J&J

> Hospitalization and death numbers are definitely directly connected

There has never been a RCT which showed covid vaccination reduces mortality. I believe they do but this has not been rigorously shown.

Unfortunately, even though we've had gigantic RCTs on covid none of them showed statistically significant covid-mortality in the unvaccinated population (potentially due to prescreening eliminating people who were at risk of dying), so they weren't able to show any improvement.

Numbers from the population have been suggestive, but unfortunately you can get the same graphs -- an initial spike of reduced mortality with a pronounced fall off in effectiveness -- from a simulation where the vaccine has no effect on mortality at all.

The reason for this is that our stats on the public measure time lagged mortality against current vaccination numbers. People reported dead today actually died a week before and got sick two weeks before that. When the increase in new vaccination is high, you will overestimate the size of the population for the people who died and falsely think the vaccine is more effective than it is. And you end up with your 'per month effect' -- the same statistical error will make the cycle nicely repeat with boosters due to the same population size error for the newly boosted population.

This is the sort of bias that is structurally eliminated in RCT design and hard to avoid in population monitoring.

If anyone wants more details, I assume you’re referencing this recent blog. If you haven’t seen this, you’ll love it because it makes the same argument: https://probabilityandlaw.blogspot.com/2021/12/possible-syst...

Hadn't seen that! but, indeed, it's the same point.

We need all-cause mortality stats from vaccinated vs non vaccinated populations but they won't give us these without fighting for it. For instance, Pfizer's all cause data from their initial trial was higher in the vaccinated group. So they then went and vaccinated the control group thus destroying any chance of long term study in this population.

The good thing is you don't need a RCT to see that vaccines are effective against mortality. For this you just have to talk to any clinician who is witnessing this winter wave and let them tell you about the difference in age profile of people on the ICU.

Or you look at incidence and observe that with even higher incidence than last year, we do have reduced mortality overall.

This is a Human Challenge Trial: have vaccinated participants exposed to either covid or placebo (rhinovirus)! There are heavy ethical dilemmas here, even when using young and healthy candidates. IIRC there was one Human Challenge Study being run in the UK, though they've been awfully quiet for months.

> Aren't antibody titers just one measure of immunity?

Yes. But Omicron just came out 3 weeks ago.

--------

We start with the quickest measures of immunity. As better data comes in, we change our opinion. The gold-standard is a large-scale, multi-month A/B test. There simply hasn't been enough time for that to be created.

If these smaller tests prove adequate, we probably will skip the large-scale test... much like Alpha and Delta, it seems like these variants don't last very long in practice. We just barely finished studying Delta's effects across a variety of treatments, and all of that data is about to become obsolete with a new variant.

> We start with the quickest measures of immunity. As better data comes in, we change our opinion.

This is exactly the problem with pandemic messaging. Too many claims based on garbage data that end up being wrong later. The result is a population that doesn't trust its government's guidance.

Vaccines were supposed to end the pandemic. Then it was they would keep you from getting sick. Then it was you'd still get sick, but you wouldn't spread it. Now it's you'll still get sick and you'll still spread it, but you won't die.

> This is exactly the problem with pandemic messaging

There's two parts to the pandemic. Gathering information, and spreading information. You need to spread the currently known things, so that scientists know what else to look for.

Welcome to the world of science and learning. You know one thing, and then it changes as new tests come in. Its impossible to get to the truth from the beginning in one step.

On the contrary -- welcome to the world trust building.

If you only know one thing, you keep your mouth shut until you know more. And if the thing you know isn't actually known, like how effective the vaccine really is, that goes double.

Notice that doesn't require you to "know the truth from the beginning in one step." It requires the people in charge to show some restraint.

You only get so many opportunities to be wrong before that trust is eroded.

Damned if you do, and damned if you don’t.

> And if the thing you know isn't actually known

Who do you want to be the arbiter that gatekeeps this information and decides the science is strong enough that you “actually know”?

“ If you only know one thing, you keep your mouth shut until you know more. ”

So hiding and covering up information is the way you think scientists should build trust, rather than being open and also clear about the limitations?

The lack of trust has nothing to do with scientists publishing data and everything to do with hucksters who misinterpret or lie about it to spread anti-vaccine panic or “government control” conspiracy theories.

The lack of trust in these situations seems to come more from how many people perceive the world of science. Many people seem to think once science has an answer it can't be wrong, and it's difficult to change, when it's more or less the complete opposite. That's what we've been taught in school. No one has been taught about how many studies turned out wrong or are easily misleading, or how to study papers and make research.

I blame education for that, for it doesn't properly teach you how to understand science. Science is taught like a Bible, when it should be taught as something people created and it's error prone.

And that's why academics shouldn't be the face of policy making. But I guess they liked the spotight too much to step out of it.

Not an immunology expert, but the focus on antibody titers seems to reek of corporate conflict of interest. It's pretty well understood that antibodies will break down and mostly fall to undetectable levels after a few months of an infection (in most cases, and in individuals who actually produce antibodies, not everyone will such as immune-compromised people) , but there's a huge financial incentive for vaccine producers to focus on these studies because it paints the picture that people need continuous boosters for protection. That being said, it's harder to detect other forms of immunity such as memory T and B cells, so it's not like the studies are completely disingenuous, it's just easier to do the studies that way.

At this point in the pandemic, I think full immunity shouldn't be the goal for most individuals. COVID and it's variants are never going away, so unless you are high risk, live with someone who is high risk, or travel a lot, the first round of vaccinations should be good enough to prevent serious illness in most individuals for a long time, at least until a variant that changes the spike protein enough comes around. At which point, to my understanding, the efficacy of most vaccines will drop significantly below natural infection, as most target specific protein structures on the virus capsid (in this case, the "spike protein").

Your first sentence is contradicted by the last sentence in your first paragraph (which is correct).

B-Cell immunity is much much harder to detect and cannot be done in any test given to the public. It's also difficult to determine from a positive b-cell result whether that person will have a strong or weak immune response - and how soon.

I think everyone in the immunology community is aware of the limitations of antibody tests, but I think it's wrong to attribute how it's portrayed in the media as corporate conflict of interest.

My impression is that it the media needs simple stories to build their narratives and cannot complicate things with b-cell immunity.

I agree with everything else you said, but I think the story for yearly (maybe bi-yearly) covid vaccines, as we have with flu, have a very strong case even given immunity memory cells.

The sentences don't really contradict, both can be true (though I will concede the first sentence is not immediately relevant to this particular study). My whole point is that the focus on immunity (vs mild cases) by vaccine manufacturers is potentially misguided and incentivized by selling more boosters.

I have a few relatives in the medical field (all vaxxed and boosted) that have explained the booster shot is just more of the same stuff - they haven't had time to make a new recipe.. so isn't this just the same study all over again? i.e 2 shots had high protection in the beginning and waned over time. Can we expect the same from the booster shot?

My assumption at this point is: probably, but the immune system is complicated so nobody's really sure.

They are comparing 3 weeks after second dose and 4 weeks after 3rd dose. Presumably efficacy drop over time after vaccination is not in scope.

Not enough time has passed under observation to actually determine if it will wane similarly.

The important bit is Omicron. Since as you say the recipe is the same it is an open question whether these vaccines can offer the same protection as for delta (and for how many doses)

I think immune response doesn’t necessarily work that way. It’s possible the third shot could improve immunity for a longer time frame of 1-3yrs.

I think I read there is also a new omicron specific mRNA vaccine in the works too.

From reading around (not a biologist), I get the impression that there's some kind of super-linear immunity building, not just waning protection. Standard children's vaccines often have a few doses, and not evenly spaced.

Soo... you're building up better immunity against the "baseline" virus with each dose. That immunity translates to some (reduced) immunity to the variants. But if the "baseline" is high enough, you can afford some drop in efficiency.

Perhaps in some ideal world, the boosters would be tuned to the variants. But as you say, they would need to be re-tested etc. Cf. the AZ vaccine, which through some arcane process causes (extremely rare) blood clots, it's probably hard to verify ahead of time a modified vaccine wouldn't suffer from such side effects.

My understanding is that there is poor evidence that any of the vaccines cause a statistically significant increase in blood clots over any other vaccine-- that the act of getting an immunization can (very rarely) trigger a blood clot regardless of what it is and COVID just happens to be in the hyper-sensitive spotlight.

It is likely that the cause or at least a cause of rare blood clots has been found. There is a chance that adenovirus used to make vaccines can bind to a specific clotting factor in the blood which then in rare cases may be attacked by antibodies created by the immune system to fight the infection.

https://www.biospace.com/article/researchers-find-possible-c...

The immune response to the booster isn't necessary the same as the response to the second dose, so no, it isn't the same study.

One impact is that antibody levels are higher after the booster than after the second dose.

I think there are two schools of thought, with little evidence so far to make one dominant.

What the press seems to be assuming is that it's as simple as the immunity from vaccination simply wearing out over time. But there's at least one alternative explanation.

The alternative is that the timing of the second dose was less than optimal. With little experimentation to guide the authorities, the 4-week delay was chosen in part to give a quicker timeline for vaccination. If they'd said, say, 2 months or 6 months, then we would have been that much slower getting to even that level of immunity, so it was a conscious compromise. But what if the optimal gap between shots really is 6 months, and because the booster achieves that, the effect will be more permanent?

Like I said, not enough is known for sure, but there is some reason to believe that the latter explanation may be true.

We should have the data to study that since some countries decided to wait longer between doses. The UK and Canada focused on getting as many first-doses into arms as possible before folks were eligible for a second jab.

There are studies that show, that you do not have much protection against an infection half a year after your second dose. This is true for all available vaccines in the western world. You probably still have protection against a severe outcome, but not against getting infected and thus spreading the virus.

A third dose, even of the same stuff, will again increase your amount of antibodies and therefore lessen the chance of an infection in the first place. Using a different vaccine as third dose seems to offer even more protection.

Expert on tv explained it just yesterday.. 3 shots is actually what you need for most vaccines and is the common procedure for most if you remember..

1st shot "warns" your immune system 2nd shot really triggers your immune system (that's also why most people see strongest side effects here) 3rd shot then makes your immune remind, and massively increases B+T lymphocytesmemory memory cells

So yeah, you can expect a lot from it.

> Expert on tv explained it just yesterday.. 3 shots is actually what you need for most vaccines and is the common procedure for most if you remember..

The same so called experts that will say that now you need the 4th dose, the 5th etc. It's now obvious that it's a vaccine as a service.

Pfizer ceo's hinted at it last year, saying it would probably be recurring every 6 months.

That’s… fine? I don’t care if I have to get a jab every 6 months. I don’t care if Pfizer and Moderna make a ton of money off this—they deserve it.

That's cool, you can give them as much money as you want. My problem is when it is me giving them the money (directly or through my taxes)

No its not fine because not everyone reacts well to these vaccines. I know numerous people, including myself, that have had crippling heart inflammation after their second dose. I can apply for an exemption but ultimately that does little for what rights I am afforded.

People are being left behind, and its not okay.

And I know people who died from Covid, who'd be alive today if they'd took the vaccine.

The difference here is no one is forcing you NOT to take the vaccine.

But I did take the vaccine, twice. It gives me great anxiety to think about taking it again given what I have gone through. My situation improved significantly but I might not be so lucky next time. I shouldnt have to weigh up potential damage to my heart, versus my right to freedom of movement (im an expat).

Personally im holding out for Novavax now.

What do you suggest as an alternative? This is the current state of the science as far as Covid-19 is concerned. There will most definitely be different types of vaccines with longer lasting immunity [1] and anti-viral drugs [2] in the future but this is the best we have at this time.

[1] https://www.clinicaltrialsarena.com/news/emergex-trial-covid...

[2] https://www.npr.org/2021/12/06/1061902658/what-a-new-antivir...

I appreciate the concise explanation.

Is there data yet that demonstrates what you describe is indeed the effect? Or have 3rd doses not yet been deployed widely enough and for long enough to know?

It took just weeks after the virus was DNA sequenced to make the first vaccine. The trials are what took so long. The vaccine existed before we started shutting stuff down in the US.

https://covid19.nih.gov/news-and-stories/vaccine-development

This paper from Africa Health Research Institute shows a 41x reduction in effectiveness of pfizer vaccine for omicron.

https://www.ahri.org/omicron-incompletely-escapes-immunity-i... https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021...

This preprint also shows reduced antibody neutralization of omicron in comparison to delta (including for double vaccinated + previous infection).

Note the sample sizes for all these studies is small. 12 participants for the AHRI paper and 8 to 20 per group for this one.

https://www.medrxiv.org/content/10.1101/2021.12.07.21267432v...

Sample size doesn't really matter much in this kind of study.

Ideally you'd match it to some population of interest. For my own medical affairs, I don't care what grand-pappy's results are here, I want to know how cousin Tim fairs.

Why not? I’m no statistician, so my basic understanding is you should always prefer bigger sample sizes to ensure statistically significant findings.

This paper doesn't even attempt to measure effectiveness. It measures neutralization titers which is a totally different thing.

Interesting. So far the Omicron variant has shown itself to be mild with minimal hospitalizations and 0 reported deaths worldwide.

Is there even a need to vaccinate at all? It would seem this is the variant we would want to spread worldwide and let it take over the more dangerous strains.

From what I've learned about the previous variants, hospitalizations are usually delayed by as much as two weeks following the increase in cases. The increase in deaths would likely follow a couple of weeks after that.

I'd still remain careful but agree the data we have now look promising. I also agree that if the Omicron variant is less dangerous it would be advantageous if it took over the delta variant

I think you mean a need to vaccinate against it specifically, but to be clear, we DO need to vaccinate to prevent serious hospitalization.

There isn't a need to vaccinate. But there are many, many leftover doses to sell. Scare the people, and sell them the "solution". Rinse and repeat every 6 months.

> It would seem this is the variant we would want to spread worldwide and let it take over the more dangerous strains.

We don't want any variant to spread worldwide because with each infection it has the potential to mutate and turn into another (sometimes more dangerous) variant. That's how Covid-19 came to existence in the first place, mutating from a relatively harmless Coronavirus.

Some provisos - it can be non mild in the unvaccinated so it's still worth having a jab even if it doesn't stop you catching it. Also there's a bit of uncertainty - there probably have been some deaths. However I'm optimistic it may spread and replace delta.

Isn't it a little suspicious that they claim more of their existing vaccine will protect that well against the new variant?

I don't want to question the rigour of their scientific testing, but it might be good to have independent tests done. Of course in parallel to giving out more booster shots, which can only help (by an unknown amount).

If they said they people will need a new vaccine (which with the current mRNA tech will be relatively quick), I can imagine a similar comment pointing out suspicion that they want to sell something new.

Doesn’t make sense for them to market the current vaccine as still working if it’s not. Eventually more real world data will be coming in and it’s not something to easily hide from.

First neutralization test results posted by the Sigal group in Durban and the Ciesek group in Frankfurt agree with the BioNTech/Pfizer data.

Sigal did not test triple vaxxed.

Why haven’t they updated the vaccine? I thought one of the major benefits of this technology was the ease with which you can modify them.

Pfizer are on it (1). They estimate that it takes around 3 months. Which actually is really easy.

And the others are following suit in similar timeframes (2)

The hard part is deciding if this variant is the one that you're going to vaccinate against for a year or more. That takes data, which also takes time.

1) https://www.theguardian.com/society/2021/nov/26/biontech-say...

2) https://www.reuters.com/business/healthcare-pharmaceuticals/...

https://www.independent.co.uk/news/uk/omicron-oxford-covid-a...

Each successful varient tends to be the ancestor of the next successful varient.

That means if you develop a vaccine against any successful varient today, it will be a closer match than one made last year.

As I understand it, none of the existing major variants is an ancestor of Omicron - their closest common ancestor is quite a way back in the pandemic. Alpha and Delta weren't particularly closely related either.

Is there a good reason that they haven't updated their vaccine for Delta, which has been out for much longer than 3 months? Over 99% of cases in the US are Delta now, which the original jab wasn't designed for.

Boosting with the original vaccine was effective for delta.

We do have a Delta-specific jab though that has gone through trials. Why not release it for sale? Just to save the government money on all the older jobs they already bought and haven't used?

Not just that, but distribution and whether or not you are ready to push for every person to get the updated one or not. People will fatigue from having to keep up, especially if only a month after their last shot there is a “new” one for a new variant, and then omicron comes out and a “new” one for that. You could end up with far more boosters than actually needed at which point people will get confused or mentally burnt out on it.

I think there are some sound reasons for not jumping on updated vaccines for every variant and only ones that the original doesn’t appear sufficient for.

> Delta now, which the original jab wasn't designed for.

Current vaccines have still been "highly effective" against Delta, so I think that's why this hasn't been done: there's no point in using the big guns now when the existing weapon works well, and you might really need the big gun soon (and you can't know when).

So it's better to keep it in reserve. The question now is, is Omicron "it" ?

By their own data, it’s less effective against Delta than the targeted strain. And the massive spike in excess deaths within heavily vaccinated states/countries this past fall was a pretty good sign we would have benefitted from an updated vaccine.

"Once Delta became the dominant strain, VE went from 91% to 78% against COVID-19 infection, 92% to 90% against hospitalization, and 94% to 91% against death."[1]

[1] https://www.cidrap.umn.edu/news-perspective/2021/09/covid-19...

(Fairly) effective at preventing serious disease/hospitalization. It seems to me the original plan on the vaccines was to reduce r0 below 1 in the population as a whole, but when Delta came along we changed the metrics the vaccines were to be judged by.

Over 90% is more than fairly effective.

All vaccines are judged by preventing serious disease and death. Not meeting higher hopes doesn't change that.

The justification for a vaccine mandate is based on preventing infection and transmission (aka r0), not just disease or death. That is probably on a lot of people's minds.

How long does it take to ramp up production? I'm at 6 months and a few days since my 2nd shot. Do I get a booster now or wait a few months in hope of an updated one?

Get a booster when you can, it is worth it.

I had mine last week.

We don't know if and when there will be an omicron-specific jab, and a mRNA 3rd dose cuts your chances of bad outcome (severe illness, hospitalisation) from omicron or previous variants to a lot lower than 2 doses ever did.

https://twitter.com/PaulMainwood/status/1458020957457731585

https://twitter.com/PaulMainwood/status/1460191035531878405

I'll likely do that. For what it's worth I was not eligible for a booster where I live until very recently.

> Get a booster when you can, it is worth it.

If you are under 65 and not immune compromised, there's essentially no evidence for this claim.

If you are either of those things, there's some evidence that it takes your risk of severe illness (already low after vaccination), and divides it by another factor of ~20 [0]. That's great, but it's a tiny absolute effect, and we shouldn't over-sell it.

If you're under 65, there's essentially no evidence supporting widespread use of boosters, and the CDC ACIP was against recommending it for all people [1] (but was ignored by politicians). The WHO continues to ask rich countries not to give boosters to healthy young people, given lack of evidence and supply constraints. [2]

Not incidentally: your two tweets discuss infection, not severe illness. All current evidence is that you're well-protected against severe disease after two shots. Paper in the lancet as of last week found that boosters had a marginal impact on cellular immunity, with the primary benefit being antibody response. [3] Again, fine, but we know that antibody response wanes over time. It's completely unsurprising that you'd have more antibodies two weeks after vaccination. You'll have far lower antibodies 9 months from your third dose, too.

[0] https://www.nejm.org/doi/full/10.1056/NEJMoa2114255

[1] https://www.cdc.gov/mmwr/volumes/70/wr/mm7044e2.htm

[2] https://www.who.int/news/item/04-10-2021-interim-statement-o...

[3]https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

> a mRNA 3rd dose cuts your chances of bad outcome (severe illness, hospitalisation) from omicron or previous variants to a lot lower than 2 doses ever did.

Literally no evidence for this statement. We simply don't know anything about Omicron and boosters. This is why this press release from Pfizer is on the front page of HN right now.

If you are in that group (under 65 and no co-morbids) two shots should be fine. Getting infected, using early treatments (even controversial ones) and recovering with a dose of natural immunity is probably better as the SA study from yesterday showed.

> Getting infected, using early treatments (even controversial ones) and recovering with a dose of natural immunity is probably better

Citation needed, as you appear to be saying that a COVID infection is preferable to a vaccination, and that is an extraordinary claim. Bonus points for using " natural immunity", a loaded term.

There's good evidence that natural infection is more robust than vaccination alone, and that a combination of infection + a booster is best overall:

https://www.science.org/content/article/having-sars-cov-2-on...

That may be a silver lining, but the statement was "is COVID infection preferable to a vaccination".

COVID infection, if you're not aware, also can have downsides. This evidence does not make "lets get COVID" a good idea on balance.

For low risk groups I think it's preferable to let your immune system have a go at it. Training it on only a portion of the spike with an alpha based vax will get you into the endless booster game. Especially if you have things like ivermectin and vitamins at your disposal.

> I think it's preferable to let your immune system have a go at it.

Again, citation needed, as you appear to be saying that a COVID infection is preferable to a vaccination.

> Especially if you have things like ivermectin and vitamins at your disposal.

Are you joking? I can't tell if this is supposed to a serious suggestion for discredited quack remedies, or sarcasm.

No I am not joking. Ivermectin worked for me. Cured me of long covid rapidly after three months of suffering through it this past spring.

Quackery it is.

Well I hope you never get as desperate as I was because this inability to see and evaluate alternatives would hurt you.

I'm not suggesting that people should run out and get infected in lieu of getting a vaccine.

I am suggesting that this mad rush toward boosters-for-all is unscientific and driven by hysteria.

That still doesn't sound like a strong argument against it to me. Getting the booster might help or might not help as much as was said. Not getting it does nothing for or against you. It sounds to me like getting a booster is a safe, reasoned choice that has a good chance at offering additional protection, zero financial cost for almost everybody, and typically very mild side effects. "Don't get it because there's a chance that it might not help and almost no risk of harm" doesn't sound compelling.

> It sounds to me like getting a booster is a safe...and typically very mild side effects.

Based on what, exactly? Also, you can drive a truck through the gap left by "typically", here. People with two doses of the vaccines will "typically" never become seriously ill.

We don't prescribe (let alone, mandate) medications because "it might help and people are scared". You have to show the benefits exceed the costs for everyone for whom you are making the recommendation. And the "costs" here don't just include things like heart inflammation (which is a real risk amongst young boys, in particular), but also the societal cost of otherwise healthy people being vaccine-sick for 1-3 days post-booster. Why do that, if it isn't going to provide a real benefit?

Also, I don't know if you noticed this in what I wrote, but the WHO is practically begging rich western nations to stop hoarding vaccines for healthy people, so that poor nations can get first doses.

Meanwhile, we have a new variant...plausibly out of a poor, under-vaccinated nation. Just a coincidence, though!

The article's main point was 3 doses of the original vaccine is more effective than 2 for omicron. They expect to have an omicron vaccine available by March if 3 doses of the original vaccine isn't enough.

I totally agree with that assessment. What I am weighing, though, is that I would not be eligible for any potential omicron-specific booster for several months if I get a booster now. It's a risk/reward calculation.

Previously it wasn't deemed necessary (i.e. the original design was good and universal enough), for Omicron as far as I know tests are running, depending on how that goes and how countries decide to treat the regulatory part of updating it we might see an adjusted one now. (EDIT: "universal enough": we don't want a vaccine extremely optimized for a variant, but one that has a good chance to work well against other/new variants too, so there's a balance if a improvement against one variant makes it worse overall)

EDIT 2: apparently some small trials for modified variants are also running for Delta, so I guess this statement needs to be modified and it wasn't considered justified to rush out a new anti-delta variant, but testing is done so the findings can be used for upgrades.

They can definitely update the vaccine but it's not easy as 1 2 3 then good to go.

I thin an appropriate analogy to your question is the question "Why haven't you written your masterpiece novel? I thought one of the major benefits of a computer is the ease with which you can write and publish anything."

In the case of the mRNA vaccines (e.g. Pfizer) it is the spike protein targeted, and that has a hard time effectively mutating because most changes to it make it less infectious. Other aspects of the virus may change but the spike so far has been relatively stable.

Not an expert, but I think the problem is in the testing and distribution. Just from a public health POV, it's hard enough tracking who is getting doses of what and all the public communication about what to do that it really needs and deal with hate tweets from Rand Paul. Synthesizing the vaccine could possibly be done in a week.

That page says they are working on it and expect to have it ready for use in 100 days including the design and manufacturing but not approval.

Very curious as to how this was determined:

"Although two doses of the vaccine may still offer protection against severe disease caused by the Omicron strain, it’s clear from these preliminary data that protection is improved with a third dose of our vaccine"

Based on the latest data, not a single person has died from Omicron, so what are they using to back this up? It's possible that Omicron is less deadly than previous strains, so what they're claiming may be kinda like saying "our water is wetter"...

Their specific test was about how the immune system reacts, it says nothing about how dangerous the virus is.

Is "First Shot" "Second Shot" and "Booster" the same as 3 "doses"?

Yes.

According to the CVS person who did my booster, the booster for Pfizer is a full dose while the Moderna booster is a half dose (relative to each manufacturer's original first and second shot doses).

Worth noting that Moderna uses a larger dosis then Pfizer for the first and second shot.

And at half dose of Moderna is still larger than a full dose of Pfizer

Probably because Moderna’s original shot was already a higher dosage than Pfizers.

According to this source https://www.statnews.com/2021/02/02/comparing-the-covid-19-v... the original Pfizer dose was 30 micrograms of vaccine, while Moderna's was 100 micrograms.

If that is correct, then Moderna's booster would still be more vaccine (50 micrograms) than Pfizer's original dose.

Of course more is not necessarily better!

One wonders if another full dose of Moderna would provide even better protection, given that a correlation has been found with the dosage: https://news.ycombinator.com/item?id=28580745

It almost certainly would. But with all vaccines, there is a balance between enough and too much immune response.

Though in this case I suspect more was better. At least that’s my hypothesis for why moderna vaccine immunity held up better against delta than Pfizer

Moderna had more time between doses too.

3 Pfizers is basically 1 moderna...

Thinking seriously about this, I will ask, were these different dosages a work of collusion between these companies and the government because they were so unsure of the reaction and efficacy at a specific dose? Was it, in effect, a huge "clinical trial"?

Between Pfizer and Moderna what is the difference other than dose? Didn't they use the same mRNA? So what was the science behind them choosing different doses? Were they guessing or were they colluding?

If someone could answer my question with a logical response instead of just down voting it I would appreciate it because it is a serious question I am trying to understand about the vaccines. I am debating on getting a booster but I have a risk profile that makes this more of an issue for me.

So, what was the science behind the different doses? Does anyone know if Pfizer and Moderna used different mRNA?

They did not use the exact same mRNA sequence: https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV...

The different doses were guesses made to balance effectiveness with severity of side effects. (Earlier Moderna trials, at least, had included even higher doses, which could cause pretty severe side effects.) Their choices had to be locked in early, based on very limited preliminary trial data, in order to run their phase 3 trials as quickly as possible, to actually bring the vaccines to market quickly in 2020. They just made somewhat different bets. I think it's as simple as that.

NYTimes has some pretty great explainers:

https://www.nytimes.com/interactive/2020/health/moderna-covi... https://www.nytimes.com/interactive/2020/health/pfizer-biont...

I don't think they are paywalled. Worth a read.

Yes. Admittedly a weird way of communicating it but I think they're trying to accommodate those who are already confused. I personally think it's having the opposite effect.

I wager it's more to avoid the "what, a 3rd dose?" reaction.

"Booster" is more positive than "we told you it would be immunization, but actually it's partial and limited, and you have to do it again. Woops, now again".

Especially since people have been talking about a 4th dose.

In the context of distrust of the pharma industry, it would be easy to have the social networks to claim pfizer is trying to become the netflix of vaccine and sell shots as a service.

So they are very careful with the wording.

Booster is also established immunology nomenclature that perfectly fits the situation, I don't think it's an attempt to "spin" it.

Well, it was effective as promised against the strains it was marketed as effective against. Those strains have been effectively eradicated. The issue is Delta, and now Omicron, which developed after the vaccine was designed.

They also said the vaccine targeted the spike protein, which was said to be very unlikely to mutate since it's such a vital part of the virus and there is little room for variation.

Unlikely to mutate much. The vaccine still remains effective because the new variants still have very similar spike proteins

Given how sick the second dose made me, I'm not keen on doing this every 6 months. Not keen.

My thoughts exactly. Why suffer through 1-2 days of sickness every 6 months to protect myself against an illness that I've already had and poses no threat to my demographic anyway? Sounds like the cure is worse than the disease. I smell a rat.

Because it reduces spread and thus reduces the chance of mutations becoming dominant. The vaccine is not only about protecting the individual.

It doesn't reduce spread in a significant enough amount to make a difference. This seems especially true with Omicron and the spread through vaccinated air travellers. It encourages mutating variants to escape/prevail because it reduces severity so you are more likely to function socially and keep spreading it.

> It doesn't reduce spread in a significant enough amount to make a difference

Yes, it does.

> This seems especially true with Omicron and the spread through vaccinated air travellers.

Nobody knows yet. We don't have enough data. Anyone who says something definitive about Omicron is either basing it off of a small amount of early data, or is lying to you. Things like infection rate, hospitalization and death are all lagging indicators. We do not have enough data to make such assertions yet.

> It encourages mutating variants to escape/prevail because it reduces severity so you are more likely to function socially and keep spreading it.

This we agree on - which is why vaccination is so important. It does reduce spread. Not sure where you got the idea it does not.

---

E (to the person who responded to me): Your response was flagged and dead before I even came back to look, so it wasn't me. Nice try calling me "cowardly" though.

The vaccine does reduce spread of the virus(es) it is made for. That statement had little to do with omicron.

My second point about assertions still stands. I don't think my comment was that hard to decipher, and certainly didn't warrant calling me names.

Being purposefully obtuse about relatively simple concepts is generally not well received on HN. Perhaps that's why you were immediately flagged.

> "we told you it would be immunization, but actually it's partial and limited, and you have to do it again. Woops, now again"

This is often portrayed as something people say, do they actually? Because that's exactly how it works with e.g. the flu. It's called yearly flu shot for a reason... 'cause it's yearly.

    [x] Usually occurs in waves during winter
    [x] Vaccine is effective for around 4-6 months
    [x] Vaccine does not confer sterile immunity
    [x] Transmitted through air
    [x] Transmitted especially in crowds and enclosed rooms
    [x] Masks work
    [x] Infects respiratory tract but
        can cause severe auto-immune inflammation afterwards
    [x] Can cause long-term respiratory issues
    [x] Many people do OK being infected, but long tail of death

I strongly feel like it's the other way round. There are already diseases where we have multiple doses, like Tetanus[1]. If they said "hey, turns out we need a third and a fourth dose like with Tetanus, and then maybe a booster every 10 years" then that would be fine, and I think most people would accept that. But the word booster suggests to me they want to become (I hadn't heard the expression before, but I love it) "the Netflix of vaccine". Especially now that the EU has declared that vaccination certificates will expire 9 months after the last vaccination.

1. https://en.wikipedia.org/wiki/Tetanus_vaccine

Is there a comprehensive white-paper anywhere with sample sizes and error bars? Otherwise this seems like an anecdote.

"The sera were collected from subjects 3 weeks after receiving the second dose or one month after receiving the third dose of the Pfizer-BioNTech COVID-19 vaccine"

How do we know this study isn't just measuring the effect of that additional week? Also how many subjects was this sera pulled from? Are the subjects materially similar between the second and third dose groups?

Not exactly surprising the people selling the third dose conclude that it is needed. It's like when the waiter recommends the most expensive option.

>> Is there a comprehensive white-paper anywhere with sample sizes and error bars? Otherwise this seems like an anecdote.

It's marketing. When the vaccine effectiveness is waning the solution seems to be more of it

If it only took 2 days to create the vaccine, why do they not have an updated one? Is there another in development that targets more than just the spike protein? Why is the entire defense that vaccine?

> If it only took 2 days to create the vaccine, why do they not have an updated one?

There's a deafening silence every time somebody asks this.

From what I've been able to see, it's because regulatory bodies won't accept an update vaccine without 8 months of testing, and the manufacturers are doing the testing, but at those delays there isn't really any point.

Why regulatory bodies won't accept updated vaccines is the more interesting question.

The regulator is only tasked with approving the manufacturer's end results, I don't think they audit the production facilities or the design process. If the production process were fully transparent and the manufacturer could prove it didn't change anything except for "this one input tweak here", the approval process could likely be further streamlined -- but I don't think the authority of the regulator stretches that far, and manufacturers will likely claim trade secrets on their internal processes.

Besides, I don't expect the anti-vax crowd to be very forgiving about mistakes or unforeseen consequences of an updated vaccine. I'm perfectly happy with the regulator having very strict controls for what gets approved for rapid rollout to the entire population.

FDA absolutely reviews stated design processes and audits against these. See 21CFR211 - The perspective here is that even if we are actually pretty confident that it is just "one little tweak here", a one-letter change could have wide ranging affects when interacting with the human body.

If all you want is transparency, most governments are perfectly capable of demanding it.

Consider this ^^^ and the fact that it takes additional months just to distribute it. Then add in the fact that the virus has a very high and successful mutation rate and can persist in and out of animal reservoirs. Mass vaccination is mentally unsound but profitable.

> When the vaccine effectiveness is waning the solution seems to be more of it

Yes. That's the definition of a booster.

> If it only took 2 days to create the vaccine, why do they not have an updated one?

The article said they started clinical trials with a delta vaccine. But they found the original vaccine was effective.

I have no idea why you believe a third dose is just marketing. It is plainly obvious that immunity decreases over time, as is the case for all vaccines against flus and similar.

A booster is the normal way to handle it. If there were a way to avoid it, at least one of the many companies working on this would have created it. And one for the regular flu, too, while they are at it, which has not happened in decades.

That reminds me, I need to get my Polio booster

I didn't say it was just marketing - I was asking for additional data to shed light on how robust (or frail) this result is. I don't think there is enough in this press release.

edit: (maybe you meant to comment on that other comment on this...)

Biontech founder Livestream: https://www.youtube.com/watch?v=nojokAK2vgU

Damn thanks. I like the German accent.

Has anyone seen research around mix and match? As in which is better, stay with the original or get a different booster?

Especially mRNA followed by J&J, and J&J followed by mRNA?

Additionally, is there any benefit to Pfizer followed by Moderna and vice versa.

Yes, there's been some research in that direction, of course I can't find the link right now ... If I remember right, core result was that using the other mRNA for booster doesn't hurt and might provide a small benefit.

Most Canadians had a mix of either AZ and mRNA or the two mRNAs mixed. There's some studies you can search for, IIRC, the mRNA ones are basically interchangeable, and the AZ/mRNA mix gave better results.

There hasn't been a complete matrix. Using moderna as the booster when you started with the other two is best. In the case of J&J moderna as a booster is significantly better, pfizer slightly. However if you had moderna to begin with we don't know. There are many other vaccines out there have haven't been studied at all as well.

In my case I had Moderna, so trying to decide whether to go with J&J or Pfizer. I guess I’ll give J&J a shot.

Can someone tell if this would be a good personal/societal strategy: once you had covid, or fully vaxxed, it’s much better to be among other people, to be exposed to the virus and continuously train your immune system.

Much of that depends on who else you’re exposing. I have to be careful because I’m helping my elderly mother, and no amount of vaccination can fully protect older individuals in poor health.

If I didn’t have to worry about other people, I’d feel much more comfortable with my current vaccination status.

in this layman's view of similar past events that seems to be exactly what happens. look at previous pandemics - Russian, Spanish, Hong Kong. Very similar infection and mortality waves; elderly, predisposed, poor health were the first casualties. as it made its rounds the rest developed immunity over time, along with children being incredibly resilient. as the population turns over those with immunity have low impact encounters. The corresponding viruses from those pandemics continue to circulate today as seasonal flu and cold strains. just my 2 cents.

My main concern is that the tests were done several weeks after the dose at the moment of peak immunity. No evidence I’m aware of of how long the neutralizing antibodies last for Omicron after a booster, though it would not have been particularly difficult to test samples at 2 week intervals to get a trend line. Ideally the higher protection would last at least a few month since that’s how long a infection wave usually lasts in the population.

From reading this article I understood that they drew serum (blood plasma?) from 2 or 3 shot recipients and introduced a similar virus to COVID (pseudo virus?) into the serum because a pseudo virus acts similar but is less dangerous (contagious?) and then I’m not sure if they looked at amount of white blood cells produced. Would love for someone more familiar with the topic to give a layman’s interpretation.

A virus is introduced just to see if/how much it gets attacked. This correlates with the efficiency against the real virus, inside a human. It has nothing to do with the introduced virus being more or less contagious.

When I see threads like these with all the buried/flagged comments I get strong "dangerous thinking" vibes. I won't be taking any more of these.

Any more booster shots? Any more vaccines?

Booster shots. Something doesn't smell right. People on all sides are scared and I don't think rational thought is being applied any more.

Sounds like your gut is in the right place. I keep my fingers crossed that our governor doesn't issue mandates for boosters for us folks in the public sector. I did my part with shots 1 and 2, but I am _not_ doing this again, for a variant which hasn't even killed anyone.

If all it takes is hacker news comment threads to sway your opinions on medical topics, you were probably looking for an excuse to not take the vaccine already. Barely anyone here is an expert on this topic and if there were experts here, you would find them at the top of the thread - not buried behind moderation at the bottom.

This is a website for fans of startups and tech. The closest we get to statistics is some middleware vendor optimized for p-hacking. Applying startup thinking to mature fields is a constant source of egg-on-face for silicon valley, as demonstrated famously by IoT safety devices. [0]

The reason for large downvotes and flags in a thread like this is because there are a lot of people who think they know what they're talking about, but don't. The rigor to participate in this conversation is much higher than having a hot take on the latest MacBook. But that doesn't stop people from oversharing anyway.

[0] https://gekk.info/articles/iot.html

I bet they had leaked this article to Wall st. yesterday and that's why we saw the markets rise sharply.

Really? This doesn't look like good news to me. It's fairly positive on the effectiveness of boosters, but negative on the original doses. That would still suggest a COVID spread through the vaccinated population (the bulk of the population) with vastly less social distancing that the first year of the pandemic. The US and Europe will not get boosters to even 40% of the population before the new wave's peak.

It's an assurance that the current vaccines work + less severe cases/fatality compared to other variants. Good enough for the bulls to stay bullish.

The intense antagonism towards any criticism of the reality of corporate collusion with the news media and Wall Street on HN leaves me confused and depressed.

The moment to have any critique against capitalism there is an invisible vocieless army of downvoters to suppress any chance for reality to invade the bubble of libertarianism on here. I get it, this is hosted on a capitalist funding platform, just do not pretend this is a refuge for inquiring thought.

You really think this does not happen, that people on Wall Street do not get inside information before the rest of you suckers get it?

It isn’t criticism. The comment is unsourced speculation. The stock market moves up and down all the time, so there are tons of other explanations for what happened yesterday and there was no effort to rule them out

Not to hijack the thread: why is my post being flagged? I'm asking a genuine question!

I was linking to UK Government data here [0] and asking about the numbers.

They're not adding up. I want to know if my interpretation is correct

[0] - https://www.ons.gov.uk/peoplepopulationandcommunity/birthsde...

You gave an inflammatory conclusion "we're all being lied to!" without showing how you reached that conclusion.

Perhaps I flew off the handle. Partly due to being flagged with no reply!

The other relevant factor is that if you lead with "Ok, I'm going to get flamed, downvoted or whatever for this", people will downvote/flag the post almost regardless of what it says, because (a) it's against the site guidelines, (b) it's a tedious internet trope, and (c) it's reliably a marker of bad comments. Best to edit that kind of thing out in the future.

Find a new talking point, this one is trivial to debunk[0]

[0] https://www.ntu.ac.uk/about-us/news/news-articles/2021/11/in...

I don’t know myself, but this happens frequently. Any body can flag your posts.

Untrue, I believe you need a certain amount of karma to be able to flag.

But it's something like 20 or 25, so really trivial to hit for any genuine user. (Although it's possible there is some weighting going on, so maybe new accounts get less flagging power or something like that)

Nope, I have 213 karma and the only thing I can do is upvote comments.

Can you flag submissions?

Yes, I can.

interesting. maybe I'm misremembering and comment flagging comes with downvotes, which I guess would make some sense.

Look all the way over at "Second dose", the age-standardized mortality rate is 1.1 per 100,000 vs 5.4 per 100,000 for the unvaccinated. 5x protection against death.

Table 1, in the linked XLS file for data through 24 September. You can see that it was originally closer to 0.1 (50x protection against death) but it's gone up to 1.1 over the last few months, I'm guessing as immunity has started to wear off.

Something else to consider is that while a person may die while having COVID-19, it does not mean that is all that they died from. People in general may have several health problems, which is especially likely for an 80+ year old person. Some healthcare activities have also been postponed since the outbreak, by the patients and also the hospitals, which may have led to less healthy people.

This is indeed what Table 8 shows. The vaccinated skew elderly, and while slight more vaccinated died, they were at a much lesser risk of dying for COVID. According to that data, over 32 times less likely for their age.

To put these numbers in perspective, global death rate from car accidents is 18.2/100k/yr. 12.4 in the US.

https://en.m.wikipedia.org/wiki/List_of_countries_by_traffic...

Yeah, and this is per week data, not per year too. So one year of being unvaccinated is equivalent to 17 years of car crash risk.

They don’t like this devolving into politics, which they really need to get over because the historical fact (when this is all said and done) is that Covid was heavily politicized by both sides in a variety of countries.

I think it's more about unsubstantiated conclusions, hysterically presented.

If the original post had outlined the data points that led them to the (IMO erroneous) impression they reached, then the point could have been rebutted.

Probably I took a look at the data linked and I have absolutely not idea how he came to that conclusion.

Like if you pick a age and week and then compare the age group+week specific death rate of fully vaccinated to the death rate of the same age group+week for unvaccinated people and it at least nearly always (I haven't check all data points) very clear that the death rate for unvaccinated people is worse.

I think you should see https://www.youtube.com/watch?v=XVRfBhy5vGI

If you want to seriously discuss you should put which data points your comparing so others can also compare. When I look at that sheet and look at the rates comparing unvaccinated vs fully faccinated the death rate is lower for every age group when vaccinated.

* Comparing week ending 24th September 2021

They're comparing different/dates/vaccination rates, classic Simpson's paradox. No adjusted data shows otherwise.

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