Covid 11/11: Winter and Effective Treatments Are Coming

I was considering splitting off my analysis of the effectiveness of Pfizer’s Paxlovid, a new Covid-19 treatment pill, but it’s so straightforward there’s no reason to do that. It works, with our best guess being it is 89% effective at preventing hospitalization and death, and that’s that. Trial was halted because medical ‘ethics’ is crazy and decided we couldn’t study the pill because it was too effective. Paxlovid still needs to be approved and production needs to be scaled up, but both of these seem like near certainties. 

In the meantime, it looks like cases are heading back upwards again. There was high uncertainty (I said I’d be more surprised by no change than by some change, but it wasn’t obvious which direction was more likely) so this was definitely in the possibility space, but it’s near the top end and rather disheartening. 

There’s the usual kinds of developments on other fronts, but none of it should come as a meaningful surprise.

Executive Summary

  1. Pfizer’s new Covid-19 treatment pill Paxlovid is ~89% effective at preventing hospitalization and death, but it will take several months to ramp up production and gain official approvals before it is widely available. Effective treatment is coming.
  2. Cases are starting to increase again outside of the South. Winter is coming.
  3. Everything else about as you’d expect.

Let’s run the numbers.

The Numbers

Predictions

Prediction from last week: 442k cases (no change) and 7500 deaths (-11%)

Results: 470k cases (+7%) and 8092 deaths (-4%).

Prediction for next week (EDIT 11/15): No prediction was made this week, which was an oversight. I didn’t notice until Monday morning. If you see me forget to do this again, please point it out. I don’t look at numbers during the week and not much happened, so I’m going to put my best guess here as to what my prediction would have been, which is 507k cases (+8%) and 7,690 deaths (-5%), but given the delay this one likely shouldn’t count for scoring purposes, no matter the result.

The miss on deaths is due to a large increase in the West. On reflection I likely should have baked some of that in, -11% was a lousy prediction and -7% or so would have been a better prediction. I do think that this is still a disappointing number despite that. For cases the miss is the same size, but this seems more like uncertainty rather than mostly being a mistake in prediction. Cases rising this much this quickly was definitely surprising, and a large update on what’s likely to happen this winter.

Deaths

The jump in the West is not centered on one particular state, with several reporting the highest levels in a while. I’d like to say it is a systematic reporting pattern somehow, and I presume that some deaths from last week out West got shifted into this week. I don’t have any gears for that explanation and given it’s not focused in one state I don’t feel great about not having any gears to explain it. Still, it seems a lot more likely than this being a real decline followed by a real increase. 

Cases

The increase looks fully real. The question is not whether cases will continue increasing, but rather whether the increase will accelerate and by how much. Child vaccinations will help a bit once they come online, but that will take a while and the total size is likely small, so we are probably looking at another winter wave. 

Vaccinations 

Skipping the graphs this week.

Vaccine Effectiveness

Half doses of Pfizer produce strong immune response (MR), presumably with fewer short term side effects, and conserving supply. We could have vaccinated far more people far quicker, here and around the world, with smaller doses. Oh well. At least kids are already going to get lower doses. This will almost certainly have exactly zero impact on the doses given out in the United States, and at this point it’s too late for most of the gains from this anyway. 

Did you know the vaccines are super effective against all-cause mortality? I mean, no, that’s crazy and any such finding is super duper suspicious and presumed hopelessly confounded but it would be remiss not to holy **** check out this chart from this video:

The effect is even stronger for Moderna than Pfizer which is stronger than J&J, and second doses are stronger than the first dose alone, and it survives segmentation by age, with the control group being people who got the flu vaccine within the last two years (but not the Covid-19 vaccines). Sample size is 11 million.

Can you imagine what people would say if these statistics were reversed with even 10% of this magnitude? With 1% of this magnitude? If people were somehow dropping dead far more after being vaccinated than those who didn’t get vaccinated? The vaccines most definitely would not remain legal, and no amount of figuring out and correcting for the confounders would make any difference. That would be the end.

I want to be super clear that I don’t buy this as a ‘real’ reduction. This has to be some sort of confounder effect somewhere, or an outright error, and the more interesting question is what that is all about. Maybe the control groups here are super weird somehow. I don’t have an explanation, and assume I’m missing something. Yet this is part of a very clear unmistakable pattern that no, the Covid-19 vaccinations aren’t causing major other problems in quantity. 

Vaccine Mandates

I’ve repeatedly noted that when vaccine mandates come into effect the number of people who actually quit rather than get vaccinated isn’t always zero, but it is always quite low. Would that change if the job is more fungible, more replicable and less appealing? For example, a truck driver?

Image

This is a rather terrible place to put a mandate, since truck drivers mostly spend their time alone driving trucks and we can’t afford to lose them at the moment. That doesn’t automatically mean this calls for a carve-out, since rules need to be simple and once the exceptions start things escalate quickly. It does introduce a potential serious issue, since trucking is a potential bottleneck on much of the economy.

By default I don’t expect much impact here, for several reasons, yet there are still reasons to worry. First, here’s the case for not worrying, as I see it.

  1. I don’t expect the rules to be enforced here in a meaningful way. Carve outs don’t need to be official to work, and I’m skeptical we’ll see much enforcement at all outside of the especially juicy targets.
  2. The baseline that almost no one actually cares enough to lose a job over vaccination. We might see somewhat more but it’s still not that many.
  3. If someone does quit, they have the option to walk over to a smaller truck company and get a job with them instead. Truck driving is mostly small businesses that are constantly forming and changing (source: listening to the Odd Lots podcast), with lots of turnover and highly fungible tasks. If someone needs to get in under the mandate’s employee limit to keep working, they’ll do that, and who does what job driving which truck is presumably mostly fungible in the end. That definitely works out on the road. What’s less clear to me is whether there’s the same flexibility at the ports to transfer staff to sufficiently small companies, if those jobs are sufficiently distinct, which in some ways they might be.
  4. This has echoes of a few years ago, when everyone thought truckers would quit over monitoring devices, and basically none of them did. We actually ended up with a capacity overhang because everyone was ready for a bunch of drivers to quit and then they didn’t quit.
  5. Thus there’s an either/or dynamic to this. If This Time Is Different it’s largely because it won’t much impact the supply chain, and if it would impact the chain, it won’t be different.

I’ve seen two counterarguments to all this that give me pause.

The first is that when someone leaves a particular trucking job, they often exit the trucking industry entirely. This is weird to me given that trucking jobs seem mostly fungible and there’s high demand for truckers, but it seems there’s other good options and the labor markets in those other options are very hot, so given the impetus of job switching some people will leave entirely. Which in turn implies that their cost of leaving the job is low, and it’s more realistic that they might quit a job over the vaccine issue.

The second is that while the effect will be small, this is a market where marginal throughput and capacity changes can have oversize effects. So if only let’s say 2% of truckers change jobs, even if that would long term return to equilibrium, that could have a very large impact on freight costs or cause bottlenecks. And for various reasons, especially stickiness in the future, it’s hard to quickly adjust wages sufficiently to compensate, so there might be considerable short term additional friction where we can least afford it.

In other mandate news, as a friend asked in a locked account, what exactly is the word “responsible” doing in this sentence?

This also seems to implicitly echo multiple other fallacies, which I know Scott knows better than. There is no ‘level we need to get to,’ there are only benefits to marginal improvements, and the existence of other ways to raise levels that we aren’t doing doesn’t change the question of the OSHA rule unless we can choose those options, nor does ‘divisiveness’ represent the obviously primary cost of policy. 

Meanwhile in Singapore, they’re done paying for Covid-19 treatment for the ‘voluntarily unvaccinated.’

But the Singaporean government said Monday that it will no longer cover the medical costs of people “unvaccinated by choice,” who make up the bulk of remaining new coronavirus cases and covid-19 hospitalizations in the city-state.

The government now foots the bill for any Singaporean citizen, permanent resident and holder of a long-term work pass who is sick with covid-19, unless they tested positive shortly after returning from overseas.

“This was to avoid financial considerations adding to public uncertainty and concern when covid-19 was an emergent and unfamiliar disease,” the Health Ministry said in its statement.

Then there’s Greece, where there’s fun being had with low social trust.

It turns out that giving out the real vaccine protects the doctors from getting in trouble for taking bribes to not administer the vaccine, but that doesn’t mean not taking the bribe, that would be crazy talk, who turns down perfectly good bribe money. 

In terms of humor value and schadenfreude value, I can’t argue with Agnus’s evaluation. 

But maybe this is actually… not the best? And we shouldn’t be happy about people getting vaccinated while the doctor tells them they’re getting water, regardless of the bribery and the attempted fraud, because the one does not make the other okay? 

It’s Over

Last week’s title was The After Times, and I made much more explicit my position that for all practical purposes that involve actual meaningful health risks, the pandemic for most people reading these posts is over now that booster shots are available and kids can get the vaccine as young as five. 

So basically this, except without the surprise.

That doesn’t mean we’re done with NPIs. There will be masks and tests and distancing and other such precautions and you and especially your children will be caught up in all that, perhaps for quite a while and perhaps at great cost. So it wasn’t fully over.

In any case, perhaps I should have waited a week, because Pfizer’s anti-Covid pill Paxlovid has interim results, and modulo the time it takes to ramp up production they can be summarized this way:

Washington Post write-up is here Here’s the AP rounding up to make it sound better, also they have a quote saying it’s ‘100% effective against death’ which is not the correct conclusion from 7 vs. 0 deaths. Here’s the Pfizer announcement. 

The trial was stopped due to ‘ethical considerations’ for being too effective. You see, we live in a world in which:

  1. It is illegal to give this drug to any patients, because it hasn’t been proven safe and effective.
  2. It is illegal to continue a trial to study the drug, because it has been proven so safe and effective that it isn’t ethical to not give the drug to half the patients.
  3. Who, if they weren’t in the study, couldn’t get the drug at all, because it is illegal due to not being proven safe and effective yet. 
  4. So now no one gets added to the trial so those who would have been definitely don’t get Paxlovid, and are several times more likely to die.
  5. But our treatment of them is now ‘ethical.’
  6. For the rest of time we will now hear about how it was only seven deaths and we can’t be sure Paxlovid works or how well it works, and I expect to spend hours arguing over exactly how much it works.
  7. For the rest of time people will argue the study wasn’t big enough so we don’t know the Paxlovid is safe.
  8. Those arguments will then be used both by people arguing to not take Paxlovid, and people who want to require other interventions because of these concerns.
  9. FDA Delenda Est.

I propose the Law of Efficacy, which states that the requirement to halt a trial due to a drug being ‘too effective’ is that the drug has been approved for public use by the regulatory authorities. 

If it’s so damn obvious that the drug is safe and effective that we don’t need more data, then the authorities can make that determination. Until then, no halting trials.  

You can tell me that there’s one set of ‘ethics’ for people intertwined with randomness or who are in front of your face, and another for those who aren’t, and I will note that such arguments are obvious nonsense. I reject the Copenhagen Interpretation of Ethics

Merck’s pill was much less effective than Pfizer’s, and it was still a huge deal. Pfizer’s pill, by all rights, should change the whole game. An additional 89% reduction in hospitalization and death, on top of the gains from vaccination including booster shots, in vulnerable populations.

There is still far too much uncertainty in how effective Paxlovid is, due to the trial being halted early – the idea that we know what we need to know here already is absurd. But we do know enough that this should become the standard treatment, and it should mostly replace prevention efforts other than vaccination. 

Once Pfizer’s pill is widely available, and most who catch Covid-19 can get the treatment, on top of widely available safe, free and effective vaccines and booster shots, I can’t see any reasonable case for prevention measures that meaningfully interfere with the living of life. The cost-benefit on that does not make any sense, any more than we already interrupt our lives for the flu or any other disease. Stay home when you’re sick, get tested if you might have it and treated if you do, and all that, but that’s it. It’s a marginal concern, but that’s all it is, a marginal concern.  

Note that this means that the case for medium-term caution if a winter wave does hit is much stronger this week than it was last week. If you wait, you do get meaningfully more protected, and there’s greater plausibility that life could mostly return to the old normal within a reasonable time frame. Similarly, there’s a less stupid policy case for doing more to contain the spread and stop the wave, since stopping the wave now buys time for a meaningful change. 

I do not agree with those cases for those who have had booster shots, I think they still fall far short, but it is important to note that the arguments in favor did get substantially better. It’s a sign of how overdetermined things were before that I’m not close to changing my mind on this. 

Think of the Children

Big Bird got vaccinated for Covid-19 this week. Here’s a clip of him getting vaccinated back in 1972, so none of this is new. Yet somehow when he Tweeted (yes, Tweeted, which for a Big Bird does seem rather appropriate) about his vaccine shot, this was a big news item for a bit this week, as according to various sources such as Ted Cruz this was government propaganda being used to push the Covid-19 vaccine on children.

A lot of the responses to this from the anti-vaccine crowd are dark. Also dark humor, which only benefits from the author quite likely taking themselves seriously.

I mean the framing on that, the attention to detail. Chef’s kiss.

Ted Cruz’s offering is much less refined, but the concept is even better, so I say it still wins. I mean, that’s great stuff, only I don’t think it sends the message he has in mind.

Is this whole operation government propaganda? No, absolutely not, HBO and Sesame Workshop did this on their own. Is it propaganda? I mean, yeah, sure, I guess, if you want to call it that, is there a problem? 

Yes, there’s a problem. This horrible photographer thought a picture to remember forever justified spending a minute outside without a mask, and I’m glad I taught my daughter better than that, says proud area mother.

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Once again, that photo, I mean look at her eyes, chef’s kiss. Future meme. Let this moment be remembered for exactly what it is. She has no mouth, and she must scream.

Therefore, Emily asks the tough questions about masks.

A number of pieces have also been written about the evidence of the protective value of masks in schools. Not everyone agrees on that topic. But today I want to look at what we know about the other side of the coin, which is actually the question I get most frequently from parents: Are  there any downsides to mask wearing for kids in school or child care?

I mean. Open mouth. Close mouth. Boggle. I mean, sure, measure the magnitude of the downside, but asking whether there are any downsides at all? I mean, seriously, have you met a child? Have you even met a human being? What in the world?

When people discuss possible concerns with masks for kids, there are a few key issues that are raised:

Interference with breathing/respiratory health

Interference with social development (ability to read emotions and interact with friends)

Interference with intellectual development (learning to speak, learning to read, learning in general)

Concerns about students with disabilities

Yes, yes, all of that is good, that is an excellent list of some of the downsides one should measure. It reminds me of nothing so much as an Effective Altruist trying to measure the advantages of an intervention to find things they can measure and put into a report. Yes, they will say, here is a thing called ‘development’ so it counts as something that can be put into the utility function and we can attach a number, excellent, very good. Then we can pretend that this is a full measure of how things actually work, and still imply that anyone who doesn’t give enough money is sort of kind of like Mega-Hitler, especially given all these matching funds. 

If you think you need to talk about Charles Darwin and the role of facial expressions in emotional development to understand that it’s not a free action to have to wear a mask all day, I’m sorry, I don’t think you have met a human being, I notice I am confused, what is even going on. No, that’s wrong. You’ve met a human, and you think that human hasn’t met any humans, or is willing to act as if they have not met any humans, and you’re reacting accordingly. And then, in this case, you’re forced to conclude that you can’t prove anything in terms of magnitude, so maybe masks are fine and don’t matter?

Burden of proof is a hell of a drug. So are demands for this kind of “scientific” rigor. 
 

Ministry of Truth

In potential blog movement news, as my previous post noted, I’m considering moving to Substack, and I’m now also considering Ghost. If you have thoughts on that, please comment on the linked post rather than here. This includes if anyone has a good source for making the block editor or comment section on WordPress not terrible, or a recommended comment solution for Ghost since it requires you to pick one. 

One of my considerations is potential future censorship, as this blog’s statements would doubtless have been suppressed and probably outright censored on major social networks and distribution channels such as Facebook or YouTube.  Wordpress and Ghost allow self-hosting and are effectively immune. Substack so far has taken a strong anti-censorship position, but history tells us we should worry how long that will last. 

Usually when I mention these concerns people will respond that no, that’s ridiculous, such actions aren’t taken in such cases, they have much bigger things to worry about. Except, well, no:

This is Cochrane. They are the gold standard on reviews of the medical literature. I’ve had my disagreements with them over the years, but it’s not like there’s anyone out there doing it better, unless there’s something I don’t know, in which case definitely let me know. Here is their Instagram, which has been declared dangerous and unmentionable due to ‘repeated posting of false information.’ 

So yeah. I’m going to continue worrying about such things.

In Other News

This story talks about trouble in the CDC, and I can’t figure out what it thinks went wrong beyond ‘political missteps’ and some sort of failure to get the White House to kowtow further to the CDC? It says there’s a ‘credibility problem’ and points to a few places where they outright proved not credible (e.g. said that which was not, and then couldn’t pretend they hadn’t done that) but didn’t seem to get into the systematic actual problems. 

Twitter thread from Kelsey Piper about how much one can poison the well on an intervention by suggesting people actually use it, repeatedly and loudly, simply because it probably works. Also she points out that the guidelines for using Fluvoxamine still haven’t been updated

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87 Responses to Covid 11/11: Winter and Effective Treatments Are Coming

  1. k says:

    I think you’re missing the vaccination graphs.

  2. DRM says:

    Zvi, You seem quite adamant and emotional that people recognize that children wearing masks has obvious downsides. To be clear, I certainly think mask mandates in schools in periods of low community spread, high vaccination and some measure of good ventilation are overkill, annoying, uncomfortable and should not continue. That said, I had the experience of being a teacher in a Japanese public middle school back 30+ years ago. It was quite normal for a very significant percent of the kids, and some teachers to wear masks during the cold and flu season days or weeks at a time, indoors and outdoors. It was unremarkable, no one complained, and there really wasn’t any discernible downside. I think that is important to note. Extreme and stupid mask mandates aside, masks should have an ongoing role in public health and we don’t need to make a big deal about it–properly used, there really is no downside.

    • albrt says:

      Yeah, I don’t have kids so I refrain from opining about them, but I am human and have met several other humans in my 58 years.

      I plan to keep wearing n-95 masks in crowded indoor spaces for the foreseeable future. Covid aside, it has been great not getting colds and flu, and I frankly don’t understand why anyone without a severe respiratory disability finds it burdensome at all. As you said, many humans in Asia have been wearing masks regularly for a long time.

      Best I can figure is that it’s a psychological problem. Mask wearing has unpleasant associations for a lot of Americans who’ve had difficulty processing the near-total failure of important institutions for the past two years.

      • lunashields says:

        Some people cut themselves and think it’s great. People do all kind of things to themselves, and think it’s great. You most definitely can keep wearing n95 masks wherever you want. We, on the other hand, can make fun of you for that. Both are perfectly fine things.

      • Dave says:

        Some people have sensitive noses and don’t like the smell of their own stale breath. I have always hated wearing ski masks in the winter for the same reason.

    • Tom W says:

      There’s a huge, huge difference between “kids are allowed/encouraged to wear masks while sick or while a bunch of other kids are sick” and “every kid is required to wear masks at all times no matter what”.

      • myst_05 says:

        Yep, that’s what everyone is missing every time this get brought up. If masks are optional, people are still allowed to wear one or ask their kid to wear one. And yes – there are certainly mask that are effective enough to not require others to wear one around you to stay protected.

    • cwuestefeld says:

      DRM, I hope you’ll keep a sufficiently open mind to see that other people find masks more burdensome than you do. For the record, aside from personal discomfort I’ve always (like, for many many years before all this) found mask use personally offensive. I want to be able to smile at people myself, and I think it’s a problem that I can’t see when others smile at me, or for that matter, that I can’t tell *what* expression they’re wearing. To the extent that we still communicate face-to-face at all anymore, the last thing we need is another barrier to seeing the human feeling behind our interlocutors.

      I’ll respect your desire to wear a mask, but don’t expect me to be happy about it, and don’t expect me to wear one myself. (You may insist that I stay home when there’s any likelihood I may be sick, though.)

      • dmendels says:

        Marty,

        I hear you, but I have trouble with this. Large percentages of the population don’t like eating vegetables. Does that mean vegetables have downside and we should use platforms like to argue against them? Isn’t there a point where we say the downside is not with X (vegetables or appropriate use of masks as a public health tool) but rather with the culture/systems/context/mindset that leads people to oppose X? Isn’t the right response to one’s own personal dislike of vegetables to think, “yeah, I don’t love them but they are healthy nutrition and lots of people are able to eat them or even love them so I should focus on being flexible and growing/expanding my preferences rather than arguing against them. “ Should we really decide my “lived experience” of vegetables (probably based on early childhood experience, or maybe on bad preparation) is so important that “vegetables are the problem” and not “my reaction to vegetables”?

      • TheZvi says:

        OK, that example is so perfect I’m going to simply point out that I gag when I try to eat vegetables, I can’t eat them. My body literally decides they are Not Food and causes me to gag. So if you were to pass a, let’s call it a Vegetable Mandate, where I wasn’t allowed to do basic life things without eating enough vegetables, I would literally need to emigrate to another country, it would be that bad.

    • TheZvi says:

      I’m happy to have masks play a role in public health (e.g. at hospitals, or if you’re actively sick, or what not) and I agree you can get used to anything – a lot of people dress up in suit and tie every day, and it’s fine. It has its upsides. But it’s not free, it’s a cost, and it’s not purely “psychological” although that would count too. Of course, if you personally want to wear a mask, I’ll mostly support your right to wear one for as long as you like, wherever and whenever you like, it’s fine.

      But c’mon. The idea that there’s ‘no downside’ is patently absurd. I can’t see who is who half as well, I can’t hear people as well, my breathing is worse, my ability to exert myself is worse, my glasses still sometimes get fogged up (and this has sometimes been dangerous), plus it’s one more thing I have to constantly check on, and that’s MY mask. My kids masks mean fighting constantly with kids and taking up cognitive space that could be used for other things. I’m confused how ‘no downsides’ can be a real position.

      I thank you for making it clear that stage four of the clown makeup (“X is good actually”) is out there as an opinion.

      • dmendels says:

        Zvi,

        I respect your “lived experience” but looking at roughly 100 years of widespread use of masks for public health in Japan I can’t find any data that there has been downside for individuals or society. If there was, after 100 years, you would expect to see some evidence of it in health (or mental health) data, GDP, productivity, anything.

        Don’t get me wrong, I oppose the stupid use of mark mandates where they aren’t necessary or well designed. And there has been a lot of that. And I personally prefer not to wear one. Just think it is a mistake to conflate that with arguing there is some material “downside” to masks in the absence of any evidence (besides some people’s “lived experience.” (Feelings, anecdotes, etc)).

      • dmendels says:

        One additional perspective on this. I have had a mild phobia of needles since I was a kid. I had a hard time psyching myself up to get the shot. That’s my lived experience. But I wouldn’t then go out on a public platform like this and get people riled up about the downsides of vaccines because of my personal experience. I can differentiate between the fact that I find vaccines quite difficult/unpleasant, and my rational understanding that this does not constitute a material downside for vaccines, vaccines are almost pure upside for everyone except a tiny minority that have very particular medical conditions. Masks—used appropriately—are roughly the same.

      • TheZvi says:

        Ah, I see.

        So there’s a motte-bailey situation (or a different definition situation) where it’s something like:

        Motte: Masks are not so expensive to wear that the share of mask wearing shows up unmistakably in the GDP numbers, it’s not this terrible crazy burden that ruins your entire life.

        Bailey: There are no ‘real’ downsides to masks, it’s all in your head, they’re like vaccines.

        Alternatively, one could say this is an isolated demand not only for rigor but also magnitude. You’re welcome to have last word and so on but committing to stop commenting here, if it’s worth me continuing I’ll do so in a main post.

      • dmendels says:

        It was a good faith point, not a motte and Bailey or isolated demand for rigor. Your response is odd.

        If I detest X and see all sort of problems with X but then I see hundreds of millions of people do X over 100 years for the benefit of society at large with no meaningful evidence of downside, measurable or even anecdotal, my reaction is to adjust my priors and think, “damn, maybe I am the problem and I need to be more flexible.”

      • Matty Wacksen says:

        Replying to @dmendels:

        >no meaningful evidence of downside, measurable or even anecdotal,

        Consider the following evidence of downside: in places where there are no mask mandates, at least 50% of people don’t wear a mask (anecdotally, from visiting one of these places, ymmv). This means, these people *measurably* think that masks are worse than the risk of covid they would prevent. Their preferences *measurably* show that masks are not worth it for them.

        >And I personally prefer not to wear one
        >conflate that with arguing there is some material “downside”

        There’s your “downside” right there. The *only* thing that matters in a certain utilitarian worldview is people’s “lived experience” or preferences. It’s kind of silly to claim that preference isn’t some kind of “material downside”. Prices themselves only represent preferences, are prices now not “material”? What does “material” even mean here? I mean it certainly doesn’t mean “measurable”, because you saying “I prefer not to wear a mask” is certainly something we can measure…

  3. lordfrezon says:

    The strongest sign to me that the pandemic is over came last weekend when I went to my local Chinese restaurant. Since they’ve had their doors open last November (as opposed to handing food through the window), they’ve had a sign necessitating wearing masks, social distancing, and mandating only 4 people inside at a time. The employees, including chefs in the back, have worn masks since last year.

    Went in this past weekend, sign is down, masks are off.

  4. Donald Fagen says:

    Hey Zvi, wondering if you saw this and what you think.

    https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785832

  5. Graham Blake says:

    Aren’t there plenty of plausible ways in which vaccination can reduce apparent non-COVID related mortality? Perhaps the rate of heart attack and stroke in the months post-COVID infection is higher, and those deaths will not be attributable to COVID. Prevent COVID infection in the first place and you prevent those follow-on events, leading to an apparent reduction in non-COVID related mortality. There could be any number of potentially lethal conditions or events that are more likely to affect a person in the months following a COVID infection that the vaccinated will inherently be less vulnerable to.

    • TheZvi says:

      If that’s true then we’d see a lot more excess mortality, right?

      • Graham Blake says:

        How much more? My impression is that throughout the pandemic there has been significant excess mortality above confirmed COVID deaths in most regions of the world, including the US. With no attestation to data quality, Our World in Data tallies a cumulative excess mortality in the US through September 26 of 796k, and confirmed COVID deaths at 689k through the same date. That’s 13.4% of all excess deaths – by that measure anyway – that need to be accounted for. I do not have the time right now to figure out how to convert the numbers in that study to estimate an associated excess mortality number and verify it falls within the 0-15% of all excess deaths range, but it would be kind of shocking to me if the numbers cited in that study required those “extra” apparent non-COVID deaths to be HIGHER than 15% of all excess mortality since Jan 2020.

      • Graham Blake says:

        Plus there’s potentially a confounder in the other direction – the relative lack of influenza mortality since the start of the pandemic. I don’t know how well our excess mortality estimates factor in the reduced influenza mortality, but if they don’t, then the baseline expected mortality number should be adjusted down, giving us a larger pool of excess mortality to account for beyond confirmed COVID deaths.

      • Matty Wacksen says:

        Replying to Graham Blake:

        >With no attestation to data quality,

        Btw if I’m not mistaken, I believe Australia, without any significant amount of covid, has had significant excess mortality.

  6. > This includes if anyone has a good source for making the block editor or comment section on WordPress not terrible

    I put this on LW a while back: Use a single “classic block” for the entire post, and it functions like the old WordPress editor did before they introduced blocks.

    • TheZvi says:

      Yep, that’s a second best solution but it means giving up most of what WP can actually do that’s unique. I did manage to get that working though, thank you.

  7. I publicly admit to being wrong.

    Also thanks for helping me understand airflow, thanks to your advice I convinced my Judo instructor to host Judo in the park rather than at his Gym.

  8. Zvitamin D3 says:

    Zvi, could you please advise when a person should consider getting a booster shot (and what kind of a booster shot) based on their age, overall health status, time elapsed since the second shot, and the monthly risk of infection? I wish there was a microcovid-like calculator to determine that.

    Also, is there any hope in a daily teaspoon of ground black cumin seeds? https://c19ns.com/meta.html – FLCCC mentions 40 mg/kg of black cumin seeds daily in its protocol (as an alternative to questionable iv,ermec.tin, for prevention).

    • TheZvi says:

      If you are eligible for the booster (e.g. 6 months since 2nd shot) then I don’t see a strong reason not to get the booster other than the short term side effects being annoying. So basically my rule of thumb suggestion is to get the shot if either
      A) You are over 35 or so years old OR
      B) You have a condition that puts you at high risk, or are constantly putting yourself at high risk with your job/lifestyle OR
      C) You would otherwise worry about Covid a lot with or without need to take preventative measures, whether you’re worried about yourself or about others

      So basically, if it would let you sleep at night, or stop doing annoying things, or you’re old enough Covid actually matters to you, do it.

      The idea of looking for an ‘alternative to Ivermectin’ (yes, you can say its name, it won’t appear or anything, it’s fine) to me kind of implies that there’s demand for something that gives the illusion of safety, but that IV no longer gives that to you, so you’re looking for an alternative? I haven’t looked at the evidence on Cumin in detail but I’d be highly skeptical, the effect sizes there don’t seem plausible and I have no idea what the mechanism here would be. I also don’t know the safety profile – if it’s harmless (and do check!) and it makes you feel better about life, I mean, sure, why not?

      • In Zvitro Study says:

        Thanks. I am below 35, my family is significantly above, it’s been 4-6 months since we took our 2nd shots, but we’re also taking strong protective measures, so we’ll probably get the 3rd shot before the Fall 2022 spike (depending on the forecasts, vaccine types, and available drugs).

        I am worried about the suboptimal treatment in case of a worse infection and/or hospitalization, so I’ve been thinking about low-dose Ivermectin+fluvoxamine as a potential at-home early treatment. I know you’re skeptical about it, the mainstream painted it as a Trumpist alt-med solution, and some studies reporting positive effects were heavily compromised and therefore useless, but I find it impossible to find a single strong rebuttal addressing this meta-analysis (https://ivmmeta.com/). Why? It would close the entire disagreement among reasonable people.

        I agree it’s unlikely that black cumin seeds have such strong positive effects. They are generally quite tasty and probably beneficial for the cardiovascular system.

      • TheZvi says:

        When you know that the sample of studies of a thing has tons of heavily *intentionally* compromised stuff in it, you can’t simply throw the rest out (if indeed the meta is even throwing them all out, I didn’t check) and then combine the rest. It’s like, well, we know that this 75% of all these crypto projects are scams, but we don’t know that the other 25% are scams and a lot of them claim they are UP UP UP! Cause you absolutely cannot do that. You can still look carefully at an individual study to decide if you trust it but you can’t do a metastudy without doing a micro-examination of everything in the sample – e.g. verifying that the studies actually happened and followed good procedures. I don’t *think* it’s worth me writing up an explainer for this but if literally no one else has done it maybe it IS worth me doing a whole post explaining it as a public service?

        As for the why, presumably because the people capable of it think they’re above such things or that you can’t reason with such people, or don’t want to be seen engaging seriously with the issue, or something?

        Fluvoxamine seems like it’s clearly +EV, so on that one sure, why not.

        The big thing is, boosters allow you to cease other prevention, so you should think about how that trade-off would work, and how much prevention you’d actually be able to stop (e.g. based on those around you allowing it).

  9. Yanky Landau says:

    Hey, what’s your source on the Pfizer trail stopping over ethics concerns? The AP link you posted states

    “An independent group of medical experts monitoring the trial recommended stopping it early, standard procedure when interim results show such a clear benefit.”

    • TheZvi says:

      I’m confused, that’s the same thing. The reason they stop it early is the ‘ethical concern’ that the control group isn’t getting the treatment. Yes, it’s ‘standard procedure’ but I don’t see how that’s relevant to how insane it is.

      • Yanky Landau says:

        Ah, my impression was that the “standard procedure” implied that once you got good enough data to show that it’s working, there is no reason to keep the study going

      • TheZvi says:

        Yes, except a good portion of the time that turns out not to be true, and this is clearly one of those times – the raw number of incidents is still pretty small. It’s enough to know that it works, but not enough to be fully confident on magnitude.

    • samjlord says:

      Yeah, I think there’s a subtle difference between stopping because it’s “unethical” to give the placebo and stopping because it means the inevitable EUA will occur sooner.

      That said, I still think it’s nuts to stop the trial early, as it’s really the only chance to get clean data on this drug. FDA should require drug companies to complete the trial, but allow them to submit an EUA application with interim data.

      • Dan Elton says:

        They only stopped enrollment of new patients into the trial – the current trial will continue. The FDA can also mandate observational studies after EUA, as they often do. Your desire for cleaner data has to be balanced with how many deaths you are willing to cause to get that data. Personally I think the number of acceptable deaths is very low given the high confidence that the drug works we have already from the data so far.

      • samjlord says:

        Don’t use that “you’re killing people” bs. How is continuing to enroll people in the trial and giving half of them the treatment causing more deaths than just giving zero people the treatment while the FDA reviews the data?

        I want the FDA to expedite the EUA with he current data but ask Pfizer to continue the controlled trial for the better data. Low-quality data can kill people, too (if fewer doc/patients aren’t convinced by the data so don’t use the treatment or if it turns out the treatment isn’t actually as good as it first appears but supplants better treatments).

  10. Basil Marte says:

    Trucking: other than regulatory inertia, are there meaningful obstacles to making longer trucks (e.g. turnpike doubles, see https://en.wikipedia.org/wiki/Road_train) legal much more widely than they already are—say, on the entire interstate network?

    • TheZvi says:

      If you’re driving near them they’re pretty obnoxious and kinda dangerous, I think? I don’t think this is an obviously stupid regulation. But I don’t know the cost/benefit so maybe it’s good, I don’t know.

  11. Baisius says:

    Re: Substack:
    Substack has a bad UI. It actively detracts from my reading experience. I read Scott less now that he’s there and would probably read your blog less if it moved there.

    I won’t speak to Ghost, I’ve never read a blog there.

  12. Ivo says:

    Greek doctors not doing what they’re bribed to do benefits society by improving public health and lowering trust in bribes?

    BTW, note that cases in Europe are spiking again. The Netherlands is quite bad. Can the US expect another spike as well?

    • TheZvi says:

      On the spike I answered that in this post with a yes, I thought. I simply notice that after boosters I can’t get into a panic about it.

      There’s an exact level of effect where taking the bribe then not doing what you promised is net good, where things are exactly broken enough that this counts as helping, but oh man is it a narrow level. The world in which people are bribing each other *but can’t even be trusted then* is not a fun one – if I can’t trust you once you’ve taken a bribe, then I really, really can’t trust you to ever do anything other than whatever you damn well feel like.

      • myst_05 says:

        I’ve recently finished reading a book on Pablo Escobar’s manhunt and it talked about how the Colombian society was so broken that the President couldn’t get any of his generals to do what he wanted, as each general only cared about their own personal goals, resulting in them not doing much to capture Escobar. On the other hand Escobar himself was very efficient because his primary weapon was fear, as everyone knew the consequences of not doing what they’re told.

        So if even bribes stop working… you’re down to forcing people to do stuff by threatening to burn down their families if they disobey. Hopefully Greece won’t get there.

  13. Sebastian H says:

    Re the “responsible adults” phrase, I *suspect* he means ‘adults who are not wards of the state or under guardianship for being mentally incompetent’ and he might mean to include prisoners as well. The idea being ‘people who are able to make their own decisions.

    Re all cause mortality and the vaccine, could it be largely selection effect? The people who opt out so far are people who live lots of dangerous decisions? Combine that with really sick people who actually can’t vaccinate. Those people are probably dying from lots of other things because they are really sick.

  14. Brett Bellmore says:

    ” since rules need to be simple”

    Where they’re needed at all, it has to be said. The simplest rule is no rule.

    Anyway, it isn’t actually hard to imagine vaccination lowering all causes mortality. It simply requires modern life being sufficiently close to sterile that our immune systems are malfunctioning for lack of anything to do. Get a jab, any jab, and your immune system settles down for a while and stops causing problems.

    Alternative explanation: There’s a problem out there with ‘occult’ coronavirus infections causing general health issues, and the vaccine clears them up.

    Odds are it’s not a real effect, but if it were there are potential explanations.

    • TheZvi says:

      Those seem like as good a ‘just so story’ as anything else, if one reasons from the effect being real, but I don’t think you or anyone else reading this would have put much (e.g. >1%) probability on them without the data – it’s all very post hoc and straw grasping. But yeah, I don’t think it’s theoretically impossible it’s largely real, simply very very very unlikely.

  15. Craken says:

    Operationally ignoring Fluvoxamine for months, while ~150,000 people die just in the U.S.–another huge failure by the FDA and the entire medical establishment. That’s ~45,000 excess unnecessary deaths, and they’re still dying. The problem for the establishment now Paxlovid has been demonstrated to have such high efficacy is that, in theory, this obviates the need for vaccination for most people. And they are extremely averse to any development that reduces the rate of vaccination. Is this why aspirin as a Covid treatment went down the memory hole after a promising study >6 months ago? 3,000 died on 9/11, prompting a commission to seek after the causes and future preventives, eventuating in a useful but clearly biased report. Covid produced a couple orders of magnitude more *unnecessary* deaths than 9/11. Is there any way a commission on Covid could be staffed by people possessed of the knowledge, and neither personally nor institutionally compromised? Maybe the gentlemen of the JASON group could take it up. Or maybe a group of billionaire hedge fund mathematicians like Jim Simons could oversee it, cloaking the non-sovereign members of the team in very remunerative anonymity.

    The chart showing all-cause mortality effects of vaccination is passing strange. I would bet much of the difference is in undiagnosed Covid infections and delayed consequences of Covid infections–the study includes people with Covid infection over 30 days before death and people not known to have had Covid at death. Yet, a 3x reduction in all cause mortality in the months following vaccination seems a bit high. Also, the rate of reduction is very similar across very different demographic categories, with the exception of the 12-17 age group, whose mortality was only reduced by about 20%. But, how could it be the same reduction among 18-44 and 85+? Maybe part of the answer is that the rule of thumb for Covid mortality is that the risk of death from Covid infection at a given age is approximately the same as the risk of death at that age over the next year from all other causes. So the ratio of risk of Covid death at 40 to risk at 90 would be the same as the ratio of the risk of all cause mortality at 40 to that at 90 (about 1:70). On the other hand, vaccination rates are quite different for the elderly and the young, limiting any supposed selection effects for pre-vax health status or recklessness or whatever among the young. Yet, the reduction rate is the same. The rate of vaccination is also different for the races, with a large gap between blacks and Asians–but no effect on mortality reductions for the double dosed. The control group being flu vaccine recipients leads me to wonder: what 15 year old gets a flu shot? For that matter, who under 40 would bother? This could be one clue as to the strangeness of the younger cohorts. Among the very old, who doesn’t get a flu shot? A breakdown of causes of death in the two groups might help resolve this mystery. I suspect blood clots are more prevalent among the unvaxxed as a late Covid complication, perhaps one that could be mitigated by a few months of post-infection aspirin prophylaxis. Despite these many questions, this study ought to greatly diminish doubts that the vaccines are more dangerous in the short term than Covid infection, even for those of us who have some anecdotal evidence running the other way.

    • TheZvi says:

      My 4 year old is *required* to get a flu shot in order to attend preschool, so it should be very unsurprising that a lot of young people get flu shots. Then again, that’s an argument it’s a poor control there. Also, the flu shot is (I think) simply a win in EV terms, as in your expected amount of time feeling bad in 2019 if you get the shot is lower than if you didn’t get the shot, so yeah it’s not going to save your life but it’s still a good idea because we’d rather feel bad for fewer days on average?

      But yeah, same page in the general conclusion.

      I don’t expect Paxlovid to run into serious barriers based on the vaccine incentive argument, but if I’m wrong someone please remind me that I need to update to be a lot more cynical on several fronts.

      • Stephen Hayes says:

        If they ran into barriers, how would we as outside observers know whether those barriers were based on vaccine incentives? If some FDA bureaucrat decides this needs to be buried because it might result in less people getting vaccinated, I don’t imagine they’d admit such a motivation in public.

  16. Stephen Hayes says:

    A question on booster shots and side effects. I had miserable side effects from my Moderna vaccination (nothing medically problematic, just miserable), if I knew there was a significant chance of getting those again then I’m pretty sure a booster shot would be negative EV for me as a healthy young person. Do we know enough to say whether the fact that I got side effects the first time is evidence I am at risk for more side effects the next time, or are they best modeled as a series of entirely independent dice rolls?

    • TheZvi says:

      There’s at least some correlation. If you had a bad experience before you’re more likely to have one again. Skip if you think that’s a bad deal. Also you can ask for Pfizer, which would reduce expected side effects a lot.

    • lunashields says:

      Also, the strength of side effects seems to correlate with the strength of an immune response. Chances are you don’t need a booster, at least not yet. You can test yourself for antibody levels to verify, it’s relatively cheap – 100 bucks or so.

      • Side effects don’t have to correlate with an immune response in general. For example, this study explored using different adjuvants (basically additives to a vaccine to enhance immune reactions) showed any relationship between side-effect strength immunity down the road. The adjuvants had somewhat different results, but the side effects didn’t seem very related.

        T Mitchell & C Casella, “No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines”, Curr Opin Immunol 2017 Aug; 47: 17–25. PMC 5626597.

        Whether they do correlate in the specific case of a COVID-19 mRNA vaccine, I don’t think anybody knows.

      • lunashields says:

        This was specific to covid vaccines and unscientific sample of people I know personally, and for the _same_ vaccines, not for different adjuvants etc that you’re mentioning. The strength of side effects tended to correlate with expected strength of the immune system(ie less in older people), who would then show much lower levels of antibodies when tested few months down the road. Totally unscientific, but plausible on a surface.

  17. Did you know the vaccines are super effective against all-cause mortality? I mean, no, that’s crazy and any such finding is super duper suspicious and presumed hopelessly confounded but it would be remiss not to holy **** check out this chart from this video:

    Things somewhat like that have been seen before with other vaccines, albeit in smaller studies with smaller effect sizes. For example, somebody asked me about Alzheimer’s and vaccines last summer, so I wrote a short piece on it, digging into 2 such studies.

    Basically, there’s some mild evidence that TDaP, polio, and flu vaccines somewhat lower the risk of Alzheimers (Hazard Ratio 0.58, 95% CL: 0.54 – 0.63, i.e. very statistically significant). COVID-19 vaccines might have a similarly salubrious effect, but I hadn’t seen any claims for all-cause mortality until your evidence today.

    One potential confounder could be that people who get vaccinated and keep up with flu shots are taking better care of themselves in general, leading to all sorts of harm reduction. But really nobody knows.

  18. myst_05 says:

    Re: Pfizers pill being a good argument for remaining careful. I think this only applies if you’re in a very vulnerable group or have daily interactions with someone in that group. Based on what I can find, the pill is not trivial to make, so it would always remain restricted to the most vulnerable age groups as Pfizer is unlikely to be able to churn out the ~20 million pills/month that would be required to cover the current number of people testing positive in the US. And the pill is only effective if you take it shortly after testing positive, so it won’t save you if your vaccine fails to work well and you end up in the hospital. So unless we see news of Pfizer promising to deliver tens of millions of pills per month sometime next year, it doesn’t make sense to change one’s behavior.

    Re: Emily Oster’s post. Its funny how it entirely ignores the problem of masks simply being uncomfortable to wear for more than a few minutes at a time. Using the same logic one could argue that air conditioning in classrooms is not important, as I’m sure there’s plenty of studies of kids doing just fine in 80 degree weather. “You just sweat it out, its no big deal!”

  19. Then there’s Greece, where there’s fun being had with low social trust.

    I saw that too, and was completely weirded out by it!

    I wrote a blog post including this story largely so I could solicit an opinion from a couple Greek colleagues.

    The feedback from my Greek colleagues, at the end of that post, was interesting:

    (1) They’re a little suspicious of the story since it’s basically sourced back to a single reporter, who claims to have gotten people to talk about giving & taking bribes (which doesn’t happen much), and gotten doctors to name their patients so the reporter could interview them (which shouldn’t happen ever). That’s… fishy.

    (2) The source traces back to the newspaper Vima tis Kyriakis. That was once a very respected centrist European newspaper, but nowadays it’s more aligned with one of the Greek political parties (PASOK) and publishes only once a week.

    (3) Another source interviews some sort of police agency who claimed this “did not correspond to reality” (according to Google Translate). But they they also admitted this probably does happen, just not at the numbers claimed in tovima.

    When there’s that much thinly sourced & contradictory data, I usually conclude that somebody’s twisting the story somewhere. Basically: the deeper I dug, the weirder it got. So I stopped digging.

  20. also they have a quote saying it’s ‘100% effective against death’ which is not the correct
    conclusion from 7 vs. 0 deaths

    Well, it’s almost correct… I mean, it’s technically correct (which, as you have taught all of us, is the best sort of correct!), but meaningless until they show you the 95% confidence limits. That will be very wide, given there were so few deaths.

    I make their data out as 389 in treatment arm & 3 hospitalizations/0 deaths vs 385 in control arm & 27 hospitalizations/7 deaths.

    That means efficacy against hospitalization is 100% * (1 – (3/389)/(27/385)) = 89.00%. A bit more fiddling about with a scaled binomial risk ratio model says the 95% confidence interval on that efficacy is 66.32% – 96.44%.

    It would be nice if that were tighter, but it says we’re probably going to reduce hospitalization by 66% or so, worst case. That’s a pretty good worst case!

    For deaths, the 0 makes the simple point estimate 100% efficacy against death. (And I guarantee you, every single person in Pfizer marketing right now wants to say “100% efficacy against death”. The fact they do not say it is because they are being restrained by cooler heads.) Those cooler heads consider the 95% confidence limits on the death rate.

    I get 46.03% – 100.0%.

    The very wide confidence interval there is warning that death was a rare event and the trial is not really powered to say much about it.

    So there ya go:

    Efficacy against hospitalization: 89.00% (CL: 66.32% – 96.44%)

    Efficacy against death: 100% (CL: 46.03% – 100%)

    • TheZvi says:

      It’s technically correct according to the norms of frequentist statistics. You can put that number on a press release, and the other numbers, and as you’ve checked, their math all checks out, which is all great. But (46%-100%) is most certainly not 100%, nor is it 78%, and if I guessed I’d put it at 90% and I presume you probably would too? And that’s the point, this was underpowered, more power was valuable, we shoulda kept gaining power.

      • Actually, I would have been happy to quote a result of 100%, as long as I also could force people to look at the confidence interval, too. A confidence interval of 46% – 100% essentially says “we’re pretty sure it reduced the risk by at least 46%, probably a lot more, but it’s hard to say much more than that.” I mean, it’s in some ways a good result: there is definitely some reduction in the risk of death, and it’s probably a lot, but we won’t know until the post-approval numbers in the inevitable Phase IV trial come in.

        And there’s no way I would have continued the trial to get better numbers here, since each number means somebody died. Stopping the trial means Pfizer goes for approval that much faster, and more lives will be saved. Things like this get stopped when the numbers are already good enough for approval, and any delay will on net cost lives.

        The only way this doesn’t get approved or at least EUA’d by December is if fraud is discovered.

        BTW, generally when a trial is stopped for good reasons like this, the people in the control arm are often granted “compassionate access” to the treatment, i.e., the trial design documents will specify that they can have special access while the FDA application is being processed. So it’s not like they’re (usually) cut off cold turkey and told to wait for the FDA. I haven’t dug deep enough to figure out if that’s the case here, but it’s what I’ve seen good people do.

  21. Zvirology says:

    Replying to the very important comment by Zvi (https://thezvi.wordpress.com/2021/11/11/covid-11-11-winter-and-effective-treatments-are-coming/#comment-15382):

    The real-time meta-analysis (https://ivmmeta.com) does account for peer-reviewed studies, GMK/BBC exclusions, and RCTs. I think it deserves a separate explainer, especially when framed more broadly: how can a relatively but not exceptionally smart person quickly learn to derive the correct answers when presented with the alt-conspiracies, the faulty mainstream consensus, and the appealing meta-analysis like this one?

    Re: boosters – compared to you, I am probably more anxious (but not very much) about the subtle and decentralized suppression of results potentially indicating increased risks and decreased effectiveness of vaccines, so I’m less inclined to take a booster after feeling quite bad following the previous shots. I am obviously still anxious about getting infected and infecting my family, which – given my remote work and limited social life – makes me mostly end up in an unhealthy basement-dweller mode. :(

    • TheZvi says:

      I will once again say, if Covid is causing you to be an unhealthy basement dweller, that’s worse than a day or two of feeling bad, and you should get a booster and take your lumps. Beats the alternative. The FUD about possible “risks” beyond that is exactly that, FUD, it’s dumb, ignore it.

      As for the Ivmmeta thing… I’ll quote a bit.
      To avoid bias in the selection of studies, we include all studies in the main analysis. Here we show the results after excluding studies with critical issues likely to alter results, non-standard studies, and studies where very minimal detail is currently available. Our bias evaluation is based on full analysis of each study and identifying when there is a significant chance that limitations will substantially change the outcome of the study. We believe this can be more valuable than checklist-based approaches such as Cochrane GRADE, which may underemphasize serious issues not captured in the checklists, and overemphasize issues unlikely to alter outcomes in specific cases (for example, lack of blinding for an objective mortality outcome, or certain specifics of randomization with a very large effect size). However, these approaches can be very high quality when well done, especially when the authors carefully review each study in detail [Bryant].

      I translate this as “we include anything anyone claims unless we know of a particular reason it isn’t real or is deeply flawed.” Oh, and also ‘we don’t like formal rules because sometimes formal rules get things wrong so we decided to include things if and only if we felt like it.’ And you ABSOLUTELY CANNOT DO ANY OF THAT in a world where we’ve already found a ton of flaws and outright fraud (let alone publication bias and all that), sorry, you just can’t, the fraud you didn’t find will overwhelm you even if you’re not committing fraud yourself, you learn nothing, this is a fraud amplifier.

      Again, that’s if this isn’t simply fraud itself, which would be less surprising than it not being fraud.

      So basically, I really really really (x20) don’t want to write this, especially unpaid and without someone to assist, but maybe someone has to and no one else will, or something? Would writing an explainer actually ACCOMPLISH anything? Who would be convinced? Is ‘no one has written an explanation for why THIS PARTICULAR piece of rubbish is rubbish actually anyone’s true objection in a way that would change behavior and matter, enough that I need to do this?

      I’m actually asking.

      • Zvirology says:

        I didn’t know you had such a negative opinion about Ivmmeta. I’m not competent enough to make any strong claims; my impression was that detecting a major (but actually non-existent or negligible) therapeutic effect is unlikely while conducting a meta-analysis on 27 RCTs (330 authors, 4583 patients), while adjusting for the GMK/BBC exclusions, even when accounting for the potential selection bias. Under these conditions, the authors note 84%/68%/25% improvement in prophylaxis/early treatment/late treatment.

        Either I need to return to the 101 course in statistics (and it might be the case, I’m not taking it personally), or it’s much harder to conduct good science than most of us expect, and we cannot blame most smart but non-expert people for being either pro- or anti-ivermectin for Covid-19.

        I don’t know if writing such a piece would be worth your time (just like the hypothetical adversarial collaboration with CovidAnalysis/FLCCC), because I’m not sure if the problem I’ve originally presented concerns a sufficiently wide and/or influential audience reading your blog. But regardless of that, I’m thankful for the comment above.

  22. Feelsbadman says:

    Replying to one of Zvi’s comments:

    The real-time meta-analysis (ivmmeta dot com) does account for peer-reviewed studies, GMK/BBC exclusions, and RCTs. I think it deserves a separate explainer, especially when presented in a broader context: how can a relatively but not exceptionally smart person quickly learn to derive the correct answers when presented with the alt-conspiracies, the untrustworthy mainstream consensus, and the appealing meta-analysis like this one?

    Re: boosters – compared to you, I am probably more anxious (but not very much) about the subtle and decentralized suppression of results potentially indicating increased risks and decreased effectiveness of vaccines, similar to the way some cultural trends are being imposed with the powerful involvement of big tech. I am still pro-vax, but less inclined to take a booster, especially after feeling quite bad following the previous shots. I am obviously still anxious about getting infected and infecting my family, which – given my remote work and limited social life – makes me mostly end up in an unhealthy basement-dweller mode. :(

  23. bakkot says:

    I can only really come up with two plausible explanations for the all-non-Covid mortality result:

    1. Differences in the underlying groups. People who get vaccinated are more likely to be taking care of their health, more likely to be active members of a supportive community [which has positive health effects], etc. Controlling for “got the flu vaccine” isn’t enough to eliminate this.

    2. It’s not actually ruling out Covid-related deaths well enough. They say a non-Covid death is one which did not “occur within 30 days of an incident COVID-19 diagnosis or receipt of a positive test result for SARS-CoV-2”, but it’s plausible getting Covid leaves you more frail for the next six months even if it doesn’t kill you.

    I would have assumed it was almost purely due to the first of these, if not for the differences in relative risk between the different vaccines. I wouldn’t expect there to be serious population differences between Moderna and J&J recipients, but there’s clearly a nontrivial difference in mortality. So maybe it’s the second thing? Or maybe there is a difference in those populations for some reason I’m not aware of?

    • TheZvi says:

      I’m in a similar spot here. I do think J&J population is importantly different from the Moderna/Pfizer one, but the Moderna vs. Pfizer difference is weird as hell.

      • Agreed that J&J is different both in mechanism and target population.

        A few reasons off the top of my head for a Moderna >> Pfizer effect:

        (1) Dosing: Moderna’s dosed dramatically higher than Pfizer’s initial shots (100 ug vs 30 ug of mRNA). Dose-dependent side effects would be more likely to show up with Moderna.

        (2) RNA edits: Both Pfizer and Moderna have considerable edits to the wild-type mRNA to make it stronger as a vaccine. I’d bet they are not identical edits in both cases, so a difference there could do something. Both sequences are posted on GitHub, oddly enough. (CureVac used essentially unmodified mRNA, and dosed lower. Its vaccine was a flop, at 47% efficacy.)

        (3) Initial 2 dose spacing (primer/booster pair, not the 3rd shot): The initial 2 doses in Moderna are 4 weeks apart, vs 3 weeks for Pfizer. This may make a difference in that waiting between the 2 doses probably generates a stronger long-run immunity; 3 and 4 weeks were probably chosen as a compromise to get more people vaccinated faster. Other vaccines (e.g., Shingrix) are 6 months between doses.

        (4) Lipid nanocapsule: I don’t know the details of the lipid nanocapsules Pfizer and Moderna use to encapsulate the mRNA, but I would be very surprised if they were identical. So some immunological detail of reaction to the lipid nanocapsule could happen. The same goes for the buffers, preservatives, and plethora of other ingredients that are unlikely to be identical.

        von Moltke the Elder is supposed to have said: “In war you will generally find that the enemy has at any time three courses of action open to him. Of those three, he will invariably choose the fourth.” And so it is here: there is probably something else going on that we have no idea about now, but in retrospect will be obvious?

  24. Picture says:

    Zvi, could you please give your rough risk estimates for a rather healthy M32:

    1) 5-9 (so ~7 months) after the second Pfizer shot,
    2) 1-5 (so ~3 months) after the third Pfizer shot,

    concerning:

    a) a minor-to-moderate infection,
    b) (any) infection ending up with long Covid,
    c) severe infection (hospitalization),
    d) death?

    It would immensely help me in understanding the vaccine’s effectiveness in my age group!

    • TheZvi says:

      Rough (as in off top of head) and not in-detail endorsed.

      Unvaccinated baseline: https://thezvi.wordpress.com/2020/05/10/covid-19-comorbidity/ as a baseline, and conditional on infection, while unvaccinated, let’s round off and say 0.05% risk of death unvaccinated. Hospitalization something like 0.2%, again conditional on infection at all. Chances of being infected depends on what you’re doing and local conditions and timelines so let’s call it X%.

      “Long Covid” is a confused concept, so one can’t give a percentage for even a guess without a better definition and no one knows anything but let’s say 7% chance that you don’t feel fully better after a few months and 2% chance that this matters to your life a year later or something is my actual estimate, but with uncertainty. Conditional on Long Covid being a thing, Long Flu and such are probably also similar things.

      With 2 shots: 80% reduction in infections, further 75% reduction in hospitalization and death conditional on infection to get to 95% lower, more confident in the 95% number than the 80% number, lower bound something like 70% reduction.

      With 3 shots: Back to at least 95% reduction in infections, and 98%+ vs. infection and death, from the baseline.

      Long Covid reduction: Conditional on infection, probably a lot (>50%, maybe as high as the hospitalization reduction, on top of reduction in infections, but honestly no one knows magnitude here. If I averaged over possible worlds, 75%?

      • Picture says:

        Thank you! To put it in more illustrative terms, if we had 3 already infected groups of 100,000 otherwise healthy men (32 yo):

        Group 1: unvaccinated
        – 2,000-7,000 (?) with long Covid
        – 200 hospitalized
        – 50 dead

        Group 2: two shots
        – 500-2,000 (?) with long Covid
        – 50 hospitalized
        – 12 dead

        Group 3: three shots
        – 200-800 (?) with long Covid
        – 4 hospitalized
        – 1 dead

        Given that the numbers above don’t highlight the 80 and 95% reduction in infections for Group 2 and 3, that infections are less likely with sinus rinses/throat gargles, and that supplementation (vit. D3, C) likely helps, then both groups 2 and 3 – besides wearing masks indoors – should essentially stop worrying and start living just as the virus no longer exists, because the psychological burden takes way more high-quality life years than the potential risk.

      • lunashields says:

        There’s some potential issue with those baseline numbers. I personally know 3 people of the right age who were hospitalized, which at the .02% rate would require me to know 1500 people aged 30 before conditioning on infection, and double or triple that (at least) without it. And I’m not close with nearly enough people like that.

      • lunashields says:

        I generally like to double check official statistic with some personal observations, just to see if it’s in the ballpark. Eg. my wife and I came down with covid while fully vaccinated, at the time official story was of some 98% protection (or whatever the number was). It was immediately obvious then that this number isn’t right.

      • TheZvi says:

        I was working backwards from the death rate, but that’s probably a bug on reflection. Your chances of dying conditional on hospitalization are much better than for a 60yo, so your chances of hospitalization given the death rate should in turn be much *worse* to compensate. Still, Luna’s experience has to be an outlier, because it’s not going to be more than e.g. 20x the death rate even with very loose bounds, and the death rate is what it is, which is a 5x multiplier on the numbers below for hosptialization (death unchanged).

        The infection number at the time was 95% I think, not 98%.

      • lunashields says:

        Actually come to think of it, only 2 were hospitalized, third went to ER and was sent home with an oxygen bottle.

      • lunashields says:

        Also, that was all in Florida, which was hit by delta earlier and harder than the rest. So perhaps an indicator of the things to come.

  25. Bldysabba says:

    Hi Zvi
    I haven’t seen any discussion from you of inhaled budesonide as a potential protocol to reduce adverse effects. There appears to be a good RCT demonstrating this – https://www.thelancet.com/article/S2213-2600(21)00160-0/abstract&ved=2ahUKEwjf4NXyvJ70AhX9FbcAHSejD2gQFnoECAcQAQ&usg=AOvVaw2wLkcFP2sewvK4GFFUspMi

    I was curious to know your thoughts on it.

  26. MMM says:

    I just wanted to mention that Scott’s recent post on Ivermectin is exactly something I pestered everybody for over the course of the last few months, and I’m frustrated that the representatives of mainstream couldn’t/didn’t want to write a single piece providing such an exhaustive analysis. I consider “a cautious case for ivermectin consideration” closed on my end.

    It’s not the first time when Scott proves to be irreplaceable, but one person has only 16 waking hours each day and a lot of different obligations. He needs to have more kids than Genghis Khan with a carefully selected group of matches.

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