Covid 10/7: Steady as She Goes

For the second week in a row little has changed. The biggest news is that Merck has a new anti-viral pill that looks to be somewhat effective as a treatment. Otherwise, it should be a quick week. Which is good, since I spent the week moving (to New York City! to Manhattan! Woo-hoo!) and am quite exhausted. There were a few non-Covid things worth discussing given the lack of Covid news, but due to the time crunch I’m at least pushing them to next week.

Executive Summary

  1. Merck has a new anti-viral pill that’s promising but not a full solution.
  2. Cases continue to decline.

Let’s run the numbers.

The Numbers

Predictions

Prediction from last week: 630k cases (-10%) and 13,700 deaths (-1%).

Results: 621k cases (-11%) and 12,405 deaths (-13%).

Prediction for next week: 560k cases (-10%) and 11,500 deaths (-8%). 

Often it’s tricky to make a prediction, but this is not one of those weeks. I expect only a small error here.

Deaths

A dramatic decline outside of the Northeast indicates we have turned the corner. The Northeast number is quite unexpectedly bad and does not seem to be an obvious data error, but I’d presume it’s mostly a fluke in some non-obvious way anyway, although the accurate death count shouldn’t peak there for another week or two.

Cases

Progress continues, slightly ahead of predicted pace. There’s no reason to expect that to stop for at least another few weeks, and a good chance it keeps going for a lot longer.

Vaccinations 

There’s been a clear uptick in vaccinations, presumably due to mandates having an effect, but it’s also possible a lot of this is disguised booster shots.

Johnson & Johnson gives data overwhelmingly supporting booster shots, files for boosters. Those boosters remain technically forbidden.

Moderna plans to build a plant in Africa to produce 500 million vaccine doses per year. That’s excellent long term news (it will take 2-4 years to build because there’s no rush or anything) and reinforces that yes we could have built more capacity and decided not to.

Vaccine Effectiveness

New study out of the United States shows immunity to infection (but not hospitalization or death) waning over time (paper).

Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29–61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months.

He points out that these results are still super awesome. I continue to be highly skeptical of the idea that protection against infection declines by an order of magnitude, yet protection against hospitalization remains unchanged, which implies that the hospitalization rate for infections went down by an order of magnitude, and yes I’ve confirmed that such things are physically possible but it’s still downright bizarre. 

Most of my previous speculations about past studies and how they might have gotten their results still apply here, and I’d definitely accentuate the positive. Even if we take the result at face value, one must presume that most of these new infections are quite mild (since they result in essentially zero hospitalizations) and probably not that infectious, which is how the math is then able to work out. 

Vaccine Mandates

Mandates work to get you a vaccinated workforce in multiple ways. The obvious ones are that your workers get vaccinated in response, others who don’t want to quit, and then you fire the ones that don’t do either.

Both methods are good, but causing vaccinations is better, so it’s good to keep track of which is which and not pretend they’re the same.

A non-obvious way is that you then get to hire a bunch of people who want to work in a fully vaccinated workplace. It turns out this is rather good for business, in a labor market where it’s tough to find good hires.

Here’s a new mandate, for those who want organ transplants.  

In other news, I was informed that congratulations are due to most of my readers, you’re anti-vaxxers:

This joins the long list of terms that used to have a useful meaning, so at least some people are trying to extend that meaning, and now it’s hard to know what anything actually means.

EDIT: It seems like this change, while real, took place in 2018. So while this is totally an example of the thing, it’s not an example of the thing due to Covid. (Also edited other paragraphs to reflect this.)

Do you think the people who change the officially approved meanings of words in such ways think they are helping? I’d like to have a word for ‘thinks people should not take vaccines’ as opposed to ‘people should not be forced to take vaccines.’ Alas few can see a difference.

NPIs Including Mask and Testing Mandates 

FDA finally approves Flowflex Covid test.

It’s about time, because, well…

I wonder how big this effect was, but I don’t wonder about whether the effect size was zero:

Image

In Other News

Washington Post presents booster situation as ‘leading doctors’ asking to have boosters scaled back, and it looks like the reasoning of these ‘leading doctors’ is something like ‘because the CDC and FDA said so.’ If the authorities want people to die and you want to be an authority, you back them up.

On that note, Dominic Cummings has a post mainly not about Covid, this part seemed worth quoting here:

Just as bureaucracies resist changes to their current direction as if governed by Newton’s First Law, so they are governed by Newton’s Third Law: the more force you exert to simplify and remove ludicrous proecess, the more demented the bureaucratic resistance becomes.

How demented?

In March 2020 I had meetings in the Cabinet room to strip insane processes out of the way. What did I discover one day? That PPE equipment would not arrive in the NHS for months because we had ordered it to be SHIPPED. Why? Because ‘the rules’ said that FLYING it was ‘not value for money’ and we always follow ‘the rules’ even when they kill people. So I told them to call the airlines and commandeer their planes (all grounded) and fly them to Asia and collect the PPE and fly back. And they asked for a letter from the PM’s office indemnifying them in the event of legal challenges and/or disciplinary action. And now much of Westminster is fighting NOT to remove the insane rules but to ensure that the insanity revealed by covid is NOT used as an excuse to remove them. And they have had much success, and got the High Court to agree that avoiding killing people is not a good enough reason to move quickly. And the lesson has been duly learned — even in a crisis killing tens of thousands, make sure you prioritise the insane rules if you want to keep your job.’

The Promising Pathway Act (MR) would greatly speed up new drug approvals going forward. Not sufficient, but at least a start, and this is a good window to attempt such matters. 

Wonderful news: Merck has an anti-viral that looks like it works against Covid-19.

It takes a certain mentality to make this the first place one’s mind goes. If people want the vaccine less now that the benefits of the vaccine are reduced, then I’d ask you to consider what the alternative would mean. 

Vaccines are held to impossibly high safety standards compared to drugs. This is in part because the person was previously healthy, and partly because vaccines have become a boogeyman that drives people nuts. 

Yes, if one can contain the virus, the best thing to do is minimize circulation, but it’s quite possible we essentially failed to contain Covid-19 in the end, and it mostly burned itself out among the unvaccinated. Plus many are now arguing effectiveness against infection over time goes way down. Combine those, and it seems like vaccination is more of a ‘reduce severity’ play similar to treating the ill, and combining that with good treatment seems like a perfectly acceptable solution, at which point we wouldn’t need to do prevention. That’s what most excites me about a new treatment – that it could reduce the ‘price of infection’ for the vaccinated sufficiently to make many people sane again.

Here’s a technical explainer thread on the drug. Definitely not a full answer or better than the vaccine, but also seems better than nothing, and if I was sufficiently sick I would want it. 

Finally, a fable about epistemics and Bayesian updating.

These are two rich, powerful, world-renowned institutions, and when they reveal a lack of interest in the truth, the general attitude is a complete lack of surprise. It just makes me want to cry.

Now, don’t get me wrong, I’m not saying that Harvard or the CDC or any institution deserves our deference. What I do think is that institutions are important in our society. Harvard’s supposed to be all about the truth, and the CDC is supposed to be all about evidence and communication, so when Harvard doesn’t care about promoting frauds, and the CDC doesn’t care about garbling the evidence, that should bother us. That it doesn’t, is an indication of the sad state we’ve come to, that decline in trust that has been seen for so many institutions in this country. You could say that the decline in trust is deserved, and I wouldn’t disagree with you—indeed, over the years I’ve done my part to decrease the trust in institutions such as the National Academy of Sciences and the Association for Psychological Science—; still, it seems like a sad state to be in, where these sorts of scandals don’t even bother people anymore.

Like many pieces of news, how one should react to this news depends on what one already knew and believed before the news.

What happened here wasn’t that Harvard and the CDC stopped being interested in truth. That ship sailed a while ago. What happened here was that Harvard and the CDC’s lack of interest in truth was revealed more explicitly and clearly, and became closer to common knowledge. 

In response, the people responded that they already knew about that, and identified as Jack’s complete lack of surprise. The scandals didn’t bother people because they weren’t news. They were expected. No one was updated. Except, it seems, the author?

In the comments to that thread, someone pointed out a seriously misleading headline from the Centers for Disease Control and Prevention. This one was four weeks old and remains uncorrected and as misleading as ever. We posted on that one too.

To me, both these stories were shocking.

That, my friend, is a you problem. Most people had better models and made better predictions, and your shock is a sign you need to update. That shock is a mistake that needs to be fixed. Whereas the lack of trust is not a mistake, it is accurate. And if you think it would be better if people’s models were instead inaccurate, then who is the one who cares about truth? It’s a sad state indeed that the CDC is not worthy of our trust, but it is less sad, given that, that we no longer trust it. We’re less likely to make mistakes as a result, and more likely to do more sensible things, and perhaps more likely to fix the problem. I’m not fully in the ‘that which can be destroyed by the truth should be’ camp, but this does not seem like one of the worthwhile unprincipled exceptions.

This entry was posted in Uncategorized. Bookmark the permalink.

52 Responses to Covid 10/7: Steady as She Goes

  1. Pedestrian Force says:

    Merrick?

    • Alsadius says:

      Merck.

      This one was pretty bad for typos, but I assume that’s because he was busy moving.

      • TheZvi says:

        I was definitely in a hurry, and my brain doesn’t care about names, so whoops. Fixed. Was not, alas, me making fun of pharma companies, beyond their stupid names causing me to not care about names.

      • @TheZvi: if you’re not gonna make fun of pretentious pharma names, can the rest of us do it for you? :-)

        I wrote a piece on the vaccine names, and drug names in general.

        One of the things that warmed me up to the Moderna folk is their penchant for good names. The company itself is “Mode RNA”, which is kind of cute for the normally humorless management class. What really got me going was that apparently their vaccine will be called “Spikevax”.

      • TheZvi says:

        Absolutely, highly encouraged! But I think I need to be better at not making transcription mistakes before I make transcription mistakes on purpose like that. And yeah, Moderna is vastly overperforming on names, you love to see it.

  2. “I continue to be highly skeptical of the idea that protection against infection declines by an order of magnitude, yet protection against hospitalization remains unchanged”

    That seems to make perfect sense to me? When you get vaccinated your body starts an R&D program on developing antibodies and while they’re good after a week they don’t stop getting better for something like 6 months. But while the quality of your antibodies continues to improve the quantity wanes if you aren’t still exposed to the pathogen. But once you’re exposed again you can quickly ramp up production of those high quality antibodies after an infection, leading to protection against hospitalization but not infection.

  3. Emilio Bumachar says:

    Merriam-Webster is no stranger to changing the dictionary on the fly for culture war purposes, but that’s not what happened now. A similar definition was in place as far back as 2018, before Covid.
    “a person who opposes vaccination or laws that mandate vaccination”
    http://web.archive.org/web/20181125060933/https://www.merriam-webster.com/dictionary/anti-vaxxer

    • samjlord says:

      Came to say the same thing. Pretty sure that’s been at least one reasonable definition for years or decades.

  4. Corrin2000 says:

    Looking on Wayback, it looks like Merriam-Webster has held that definition for anti-vaxxer since at least 2018 (the first entry). While it’s a surprising definition, it’s not new.

    • samjlord says:

      Agree.

      Although I don’t even think it’s a surprising definition. For decades, a major campaign of anti-vaxxers has been to eliminate or erode vaccine mandates in schools.

  5. Dave says:

    This must have broken too late for you to cover it this week, but Sweden and Denmark are suspending use of Moderna in young people because of the myocarditis risk:
    https://www.reuters.com/business/healthcare-pharmaceuticals/sweden-pauses-use-moderna-covid-vaccine-cites-rare-side-effects-2021-10-06/

    Also there was a new Israeli study showing myocarditis in ~1/7,000 males in the 16-19 age group with Pfizer: https://www.nejm.org/doi/full/10.1056/NEJMoa2109730

    I am extremely pro-vax, but this is not a minor deal. Given that the vaccines seem to mainly be about reducing severity, not spread (which they seem to impact very little), vaccinating boys will never get us to “herd immunity” or reduce transmission enough to prevent mutations. And yes, the risk of myocarditis with Covid is still ~10x higher (https://www.aappublications.org/news/2021/08/31/covid-myocarditis-risk-children-083121) — but the vaccines won’t prevent you from eventually catching Covid (they may delay it but any young person alive today will eventually catch it) and we don’t know how much they reduce the risk of myocarditis (and other extremely rare, equally severe outcomes) from Covid.

    In my opinion this should probably close the door on incentivizing or mandating mRNA vaccinations for boys and young men, although not necessarily for girls and young women.

    • Sweden and Denmark are suspending use of Moderna in young people because of the myocarditis risk

      On the other hand, there was a myocarditits and mRNA vax study retracted last week.

      Basically, they undercounted the population of vaccinated people in the time and place they studied — by a factor of 25! So the risk went from an alarming 1 in 1,000 to a milder caution about 1 in 25,000. (They were good sports about it: announced the error themselves, frankly owned it, and retracted the paper themselves. Everybody makes mistakes, and frankly that raises my respect for this particular research group.)

      Given that the vaccines seem to mainly be about reducing severity, not spread (which they seem to impact very little)

      Vaccines do slow down spread. The CDC study saying otherwise had 2 major flaws: it studied only hospitalized breakthrough infections, and it only measured 1 time point.

      The first problem is a selection bias by looking only at the worst cases, not the typical cases. Most breakthrough infections get stopped at a much lower viral load, and thus don’t spread as much.

      The second problem is time: vaccinated people can have a high initial viral load, but they clear it much more quickly than unvaccinated people. So they may be as contagious for a day, but quickly become less infectious.

      • Dave says:

        To be clear, I do think that they reduce spread. Just not enough to prevent pretty much everyone from catching Covid at some point in the next several years.

        E.g., there is no doubt a lot of systematic error and confounding in this — https://link.springer.com/article/10.1007/s10654-021-00808-7?fbclid=IwAR2dvgbAmtND2TfSI9etmx_bF1k_t3D2oEA3c1zXJi_9k_AoBH4FZs5uhZo — but the fact that it is even possible to fudge such a result makes it seem very unlikely that vaccines will have some of the claimed effects on global transmission (e.g., making it possible for an appreciable number of people to avoid ever catching Covid for their whole lives, reducing transmission enough to make a difference to the mutation of new variants).

      • Catweazle says:

        Yes, vaccines do reduce spread. That doesn’t mean they can limit exponential growth/spread of the virus. Let’s assume a 50% reduction.

        if R0(no vax) = 1.8, then R0(vax) = 0.9, result happiness (disease dies out)
        if R0(no vax) = 2.2, then R0(vax) = 1.1, result misery (disease grows exponentially)

        And if R0(delta) = 6 or 7, vaccines need consistent spread reduction in the 90% range, which probably isn’t going to happen.

      • @catweazle, Re 90% immunity:

        As of today, the US has had over 45 million confirmed COVID-19 cases, or about 13% of the roughly 330 million population.

        One feasible, though unpleasant, endgame would be 75% vaccine immunity and 15% natural immunity from previous infection. Then you get 90% immunity in the population as a whole, neglecting overlap.

        That’s enough to cope with an effective R0 = 1/(1-0.9) = 10.

        There are of course several bugs: a lot of people have to get sick and miserable, the healthcare system has to survive more waves, the economy has to survive as well, and of course the unvaccinated aren’t uniformly separated. In the US, they clump in the South and in rural areas, so their local % immunity might be lower.

        I’d love to hear a better solution.

      • Catweazle says:

        @WeekendEditor, Re 90% immunity:

        90% population immunity (75% vaccine + 15% natural) is not a sufficient condition to reduce R0 by 90%. It simply means that 90% of the population is well protected against severe covid.

        The R0 reduction however is dependent on the VE (Vaccine Effectiveness) to infection, which back in the day was touted as being 95%, but now ends up nowhere near, more like 50% or less. Not nearly enough to get R0(delta) below 1.
        I find it curious that the original trials focused solely on infection-VE. They did not even bother to measure severe-VE or spread-VE. Especially since we’re now being told that severe-VE is what counts.

        A few recent cases appear to indicate that high levels of immunity don’t limit spread:
        – Singapore, one of the most vaccinated nations in the world, removed many measures in August. They’ve flattened their curve since then all right, just along the wrong axis:
        https://ourworldindata.org/explorers/coronavirus-data-explorer?zoomToSelection=true&time=2020-03-01..latest&facet=none&pickerSort=asc&pickerMetric=location&Metric=Confirmed+cases&Interval=7-day+rolling+average&Relative+to+Population=true&Align+outbreaks=false&country=~SGP
        – The British population tracks the prevalence of Covid antibodies in the population through random testing. 95% have antibodies. Covid hasn’t exactly disappeared:
        https://ourworldindata.org/explorers/coronavirus-data-explorer?zoomToSelection=true&time=2020-03-01..latest&facet=none&pickerSort=asc&pickerMetric=location&Metric=Confirmed+cases&Interval=7-day+rolling+average&Relative+to+Population=true&Align+outbreaks=false&country=~GBR

        I reserve judgement until I see at least one country reach herd immunity through widespread immunity (vaccination or infection).

      • @Catweazle:

        90% population immunity (75% vaccine + 15% natural) is not a sufficient condition to reduce R0 by 90%.

        That’s not quite what I meant; I did not mean a 90% reduction in R0. R0 is what it is.

        I meant that for a fixed value of R0 (fixed by virus biology and human behavior for NPIs), there is an immunization fraction h that is a reasonable goal for herd immunity.

        I used a simple SIR epidemiology model, like everybody else, to relate R0 to h, the fraction of the population that has to be immune to achieve herd immunity:

        h = 1 – 1/R0 = fraction who need to be immune for the simplest model of herd immunity.

        So if you have a good estimate of R0, you can calculate a really simple-minded goal for how much of the population needs to be immune to achieve herd immunity. If you have a fraction h of the population immunized, you’re near herd immunity as long as R0 is small enough, just by solving the above for R0: R0 < 1/(1-h).

        If we can get to 90% immunity (vaccine + natural), then the maximum R0 for which that would provide herd immunity is R0 < 10. The last estimate for Delta R0 I read was MacMillan's article at Yale Med School, reporting around 6.7. That would require about 85% immunity.

        There are, of course, reasons to be skeptical, such as:

        (1) Maybe a simple SIR model is too simple. I've seen more complex ones with more states (the most clever name was SIDARTHE, with 8 states).

        (2) Human behavior changes the value of R0, e.g., refusal to mask or social distance. If we get over-confident, we could raise the effective R0 and break things.

        (3) Vaccine efficacy could wane with time. The very, very simple model above assumes near-100% vaccine efficacy, but there are more complex ones that could also be used. I'm not convinced we've seen waning yet, since people measure just antibody levels not the response of memory B cells and T cell activation to re-challenge with virus.

        … and probably a number of other things.

        So basically that's what I meant: absent vaccination waning, and assuming a fixed R0 (no human NPI behavior changes and no new nightmare variant), then there is a fraction h of the population that is a good target for herd immunity.

      • Catweazle says:

        @WeekendEditor thanks! I’m not sure if your “VE near 100%” assumption is borne out by recent events.

      • Catweazle says:

        @WeekendEditor how for example, could one explain 95% antibody prevalence in the British population, yet Covid infections continue to run rampant?

        How could one explain that >88% of the eligible population in Singapore is vaccinated, but Covid is exponentially exploding there?

      • @Catweazle

        Re VE near 100%:

        Yes, that’s the usual assumption of SIR models. They can be haired up with more states and with probabilistic transitions.

        BTW, the funniest-ever introduction to SIR models involves modeling zombies. There are equally funny followups, which assess the “realism” of the zombie modeling by comparing to “data”, like Dawn of the Dead. They’re silly, but people actually learn from cleverly fun examples like that, and even enjoy the experience.

        Re explaining Britain and Singapore:

        Honest answer: I really don’t know.

        Hedging answer: I can imagine several reasons, but have no particular evidence that they explain either Britain or Singapore in particular. For example:

        (1) Antibody levels are a small slice through the immune system. You can even have high ab levels without immunity, e.g., after an infusion of externally produced abs like from Regeneron.

        OTOH if they showed people with competent B-cell and T-cell responses to viral challenge were still getting serious infection, then that would be worrisome.

        (2) Speaking of serious infections, I don’t personally know if those data are reporting all infections, or only the serious ones (hospitalization & death). You can be fully immune and still get a quick, low-grade infection since it takes a couple days for your immune system to recognize it and ramp up antibody generation. If that counts as “infection”, then more or less every vaccine fails, and that’s just not the case.

        OTOH if they’re reporting increases in hospitalization & death rates of fully vaccinated people, that would be worrisome.

        (3) Simpson’s paradox: Israel had a problem with this, thinking that increasing hospitalization rates among those vaccinated longest ago were because of vaccines waning. In fact, they vaccinated their elderly first, and the elderly have weaker immune systems and are more likely to be hospitalized with respiratory infections. So hospitalization rates and time since vaccination were hopelessly convolved with age. (Also, they were taking the wrong denominator, calculating Pr(vax | infected) when what they wanted was Pr(infected | vax). Morris wrote a wonderful piece at COVID-19 Data Science, working through the data. I wrote a little extension to it, calculating VE stratified by age cohorts and their 95% confidence limits to be really sure because it was such a big effect.

        OTOH if they showed that after proper stratification by confounding factors like age, people were still getting serious infection, that would be worrisome.

        There are probably other possible reasons; this is just what I can think of in 10min. I’m just being honest with you about the fact that I haven’t studied the British or Singaporean examples to know much beyond “immunology is weird and complex.” :-)

    • samjlord says:

      Clarification: Denmark is *not* suspending Moderna use: https://www.reuters.com/world/europe/denmark-says-moderna-covid-19-vaccine-still-available-under-18s-2021-10-08/

      Also, the FDA has currently not authorized Moderna for anyone under 18 years old, so Sweden and Finland are actually coming more in line with the US.

      I agree that the myocarditis risk is something to monitor closely and that the side effects need to be that much smaller in children because of their lower risk from covid. But ultimately, I think the current data indicates that the vaccines are relatively safe. I bet the lower doses in younger kids will even improve the cost/benefit balance.

      (I have supported the “slow” FDA process of really carefully confirming the safety of these vaccines. I even supported the supposedly disastrous J&J pause. Can you imagine the vaccine resistance if the FDA had stepped aside like some have called for? I’m not sure even I would be vaccinated.

      I have been annoyed with the FDA for blocking rapid antigen testing. But maybe I’m wrong about that?)

    • Catweazle says:

      @WeekendEditor how for example, could one explain 95% antibody prevalence in the British population, yet Covid infections continue to run rampant?

      How could one explain that >88% of the eligible population in Singapore is vaccinated, but Covid is exponentially exploding there?

  6. Hegels Schnecke says:

    „I continue to be highly skeptical of the idea that protection against infection declines by an order of magnitude, yet protection against hospitalization remains unchanged, which implies that the hospitalization rate for infections went down by an order of magnitude, and yes I’ve confirmed that such things are physically possible but it’s still downright bizarre.“

    As far as I understand it it’s about the place where you got your vaccine. That‘s where the antibodies linger around. So in the first month after vaccination you have amazingly high antibody counts so you‘re safe everywhere. But with time these levels drop everywhere except in your place of exposure. If vaccinated that‘s your arm muscle (so an infection in the nose can start up for a few days before you‘re saved by your antibody memory). So higher infection rates, same low hospitalisation.

    When you are naturally infected those lingering antibodies are created in your nose so the next coronavirus coming along will get stopped in it’s tracks right away. Also, once a nasal spray vaccine is available it stands to reason that it would work way better against any infection as the lingering antibodies would be left already where they will be needed. My source for this is an explanation by Christian Drosten (hiiiiighly regarded in Germany as top expert on SARS-CoV-1 and 2).

    So it doesn‘t seem too counterintuitive.

    • Dave says:

      What is the explanation on this view for why the lingering antibodies localized in the arm continue to provide strong protection against hospitalization?

      The explanation for waning protection against infection/strong protection against severe disease that I’m familiar with is that antibodies wane, but B-cell and T-cell activation does not, and that the former protects against infection while the latter prevents severe infection. https://cspicenter.org/blog/waronscience/why-covid-19-is-here-to-stay-and-why-you-shouldnt-worry-about-it/

    • TheZvi says:

      I mean yes and no. I do get this and I appreciate the extra detail I didn’t previously have. I still say it’s weird that the extra infections you get due to not having the local antibodies NEVER get as far as hospitalization, given the odds of that didn’t change, that still seems super weird and unlikely to me. Some decline, sure, I could buy that, but total?

      • SamChevre says:

        My mental model is that vaccination makes your immune response to the thing you are vaccinated against faster, and stronger. This means, in turn, that the infection doesn’t progress as far before the growth rate of the virus slows due to immune response.

        If this model is right, the pattern we seem to see makes sense: as the vaccination/infection is longer ago, the immune response is less fast, but still much faster than in a person with no immunity. In turn, this means that the number of infections doesn’t go down that much, but the sickness/hospitalization level goes down more. (Visually, model the virus load as a normal distribution with the x-axis as time: the unexposed is just a standard Z-curve, the immunized model scaled down and shifted left so the initial portion is very similar but the peak is sooner and lower.)

  7. He points out that these results are still super awesome. I continue to be highly skeptical of the idea that protection against infection declines by an order of magnitude, yet protection against hospitalization remains unchanged, which implies that the hospitalization rate for infections went down by an order of magnitude, and yes I’ve confirmed that such things are physically possible but it’s still downright bizarre.

    They are indeed awesome results, since not getting hospitalized and not getting dead should be high on everyone’s goal list.

    Infection decline vs hosp/death robustness: this is to be expected.

    In the months after vaccination (or COVID recovery), you’re basically antibody city. Infections can’t really get a toe-hold. It’s a wonderful time.

    But after a while, antibody levels decline. This is normal: you’re not chock full of antibodies to every single virus you’ve ever had in your entire life! But your memory B-cells remember them. When presented with a viral antigen, they ramp up antibody production and clear the infection. This may take a day or two, during which time you’re technically infected, but at mild initial stages.

    In other words: you still get a mild initial infection (“waning efficacy vs infection”), but you ramp up antibodies to clear it before it can do much harm (“robust efficacy vs hospitalization or death”). This is true of both natural and vaccine immunity.

    This is also a reason people are real interested in a nasal spray vaccine. If you can induce really intense immunity specifically in the nose, throat and sinuses you can stop a respiratory infection even sooner. Of course, those antibodies will fade with time, too, and you’re back to waiting on your memory B-cells to do their job.

    Your conclusion that this is “downright bizarre” is just confirmation that immunology is a really complicated, weird kludge invented by evolution. Intuition is a bad guide here. If engineers invented something like that, you’d fire them! But evolution places no premium on simplicity or elegance, just survival.

    Wonderful news: Merrik has an anti-viral that looks like it works against Covid-19.

    [BTW, Merrick/Merrik should be Merck. Unless you’re deliberately making fun of corporate pharma, in which case I salute you warmly.]

    I did a quick little reanalysis of Merck’s clinical trial result for molnupiravir. I calculated efficacy against hospitalization or death, just like vaccine efficacy, and its confidence interval.

    Conclusion: Estimated efficacy is 48.2%, with a 95% confidence interval of 20.5% – 66.5%.

    The confidence interval is so wide because the whole trial had only 760 patients.

    Also, it costs about $700 a course.

    But at just a hair under 50% risk reduction, it’s nowhere near as great as vaccines, which still reduce hospitalization or death risk by 85% – 95%. (I reanalyzed the Israeli data by age cohorts and got confidence intervals to confirm this.) So don’t rely on molnupiravir as a therapy in lieu of vaccination. But if you happen to get sick, then definitely take it and say thank you.

    On the other hand, it has to be given early, ideally before the onset of symptoms. That can only happen in the presence of frequent testing. Since it’s pre-symptomatic, people will probably have to be mandated to be tested, e.g., by employers. I don’t see people volunteering for 2 nasal swabs a week just to catch a case early enough for molnupiravir.

    • Dave says:

      Very helpful information, do you know how it compares to monoclonal antibodies on the cost and effectiveness fronts?

      • Cost of vaccines: about $20/dose, so call it $50 – $60 for 2 doses, including the cost of the pharmacy tech who gives it to you.

        Cost of a course of molnupiravir (2 tabs a day for 5 days): about $700. Just a pill, so it’s easier than a shot and WAY easier than an infusion. No skilled nursing required, just a doctor to write the scrip and a pharmacist to fill it.

        Cost of Regeneron’s mab cocktail (casirivimab and imdevimab): about $1250/infusion, plus the cost of being in a hospital or clinic with skilled nursing staff giving you the IV and to stand around knowing what to do and how to save your life if something goes horribly wrong. Ballpark maybe $2k, maybe more if another infusion is required?

        Cost of GSK & Vir’s mab cocktail (sotrovimab): about $2100/infusion, again with skilled nursing care to administer it at some extra cost.

        Cost of toclizumab (anti-inflammatory mab acting on IL-6): couldn’t dig it up quickly. It’s more about tamping down the high inflammation that does so much damage in COVID, not about attacking the virus directly.

        Cost of remdesivir (also causes genetic errors to accumulate, but is only mildly effective): $3120 for a course of treatment.

        Cost of dexamethasone (anti-inflammatory): dirt cheap, looks like about $1.71/dose and you’ll need several doses. Since it’s an anti-inflammatory, it’s not preventative nor of any use in mild or early cases. You’ll be hospitalized, possibly on a ventilator, before you see this. You’ll never notice the cost on top of the bajillions of dollars the hospital will bill you.

        That’s what I could find out about cost. Comparing efficacy… well, let’s just say it’s a LOT more complicated to get the data for that!

        So, yeah: vaccines are dirt-cheap, safe, and most effective. Clearly they are your front-line strategy for not dying and not infecting your loved ones. If you get sick anyway, the others are very fine backup strategies.

        Only molnupiravir is cheap enough and easy (a pill, not a shot, not an IV infusion) to deploy widely, as a prophylactic given to people who turn up when contact tracing an infected person. THAT made me excited when I heard about it!

        But people will whine uncontrollably about all the testing and contact tracing necessary to make that work. The whining is really starting to wear on me.

    • TheZvi says:

      $700 a dose seems trivial here, compared to what you get, and presumably it compounds with vaccination so we don’t have to choose. I find the emphasis on better/worse than vaccines kind of odd. The need to do it super early seems worse.

      • People are investigating the combination therapy synergy (that’s the technical term for it; research on synergy combinations in oncology used to be a big chunk of my job) of combining molnupiravir with vaccines (all the people in the trial were not vaccinated), and with the Regeneron antibody therapy (wildly different mechanism of action, so it’s hard for the virus to evade both), and VERY IMPORTANTLY using it prophylactically on the contacts of people who get COVID. (Also during pregnancy, with kids, and all the usual stuff.)

        If the combinations work better, and especially if it works as a prophylactic used with contact tracing, then that could be game-changing. We might be able to stop the spread in its tracks. But all that has to be tested. And since we’d mostly be using it as a preventive on healthy people, the bar will be high for safety.

        The other thing that nobody’s talking about, but which occurred to me might be important: this is not SARS-CoV-2 specific, but should apply to whole classes of RNA viruses. It works by introducing a bogus ribonucleoside into their RNA that hypermutates the virus until it can’t function. If it turns out to be more widely applicable, then it’s as big a miracle as the mRNA vaccines.

        But the logistics are challenging: you have to pre-position it in basically every pharmacy so you can get it to people quickly, and you have to do LOTS of testing of asymptomatic people find your target patients. People have to decide to accept contact tracing, and not think it’s just more government snooping. Our ability both to do logistics and to frame public health services favorably are somewhat in question, yes?

        The cost is nontrivial for insurers or the government, if lots of people take it instead of the cheaper and more effective vaccine. But if people take the vaccine, then this is a perfectly good backup strategy that won’t have to be used as often.

    • Triskele says:

      “People have to decide to accept contact tracing, and not think it’s just more government snooping.”
      For a lot of people maybe in countries other than the US, there is no incentive other than ‘for the communal good’ to participate fully with contact tracing (unless you’re in a country where they just jack into your location history) because you risk getting your friends and family locked down, isolated and out of work for two weeks if you pop on a government-run PCR test. If there’s actually an incentive for _you_ as part of the the deal, I think this is an important second-order effect.

  8. Dave says:

    Hm it seems like Zvi didn’t like this the first time, so let’s try it again with less editorializing…

    Recent study from Israel finds myocarditis strikes about 1/7,000 males after the second shot of Pfizer in the riskiest age group (16-19): https://www.nejm.org/doi/full/10.1056/NEJMoa2109730

    Also relevant, of course, is the fact that myocarditis is about an order of magnitude more common in similar age groups after infection with Covid: https://www.aappublications.org/news/2021/08/31/covid-myocarditis-risk-children-083121?fbclid=IwAR1o6uc3_m6-mDos_rzeerdxfsoC1CWrLy8MaZQJ3q1lE8pA6rVs1dIryCw

    That said, the cost-benefit analysis is more complicated than subtracting the side effect risk from the infection risk, because vaccines are not total protection against infection. If one is vaccinated and continues to be exposed to Covid over the course of one’s life, it seems unlikely that one will be able to avoid infection indefinitely. So the key question is how much the vaccines reduce the risk of severe, rare outcomes in children.

    What seems clear is that the cost-benefit calculus of injecting boys once and girls twice is positive based on what we know now. It is less clear that boys should be injected twice with mRNA vaccines. I find it bizarre that the adenovirus vaccines are not being tested in children from what I can tell. At a minimum, why not test those as well as a backup plan, in case the mRNA trials in children go poorly?

    • TheZvi says:

      I was out and the system flagged it to require approval because of the links, that was all.

    • samjlord says:

      I plan to start with a single dose with my younger boys, maybe do a second dose at 3 months or so if the safety data is looking good.

      The main benefit to the vaccine in younger kids is indeed as you say to reduce the risk of myocarditis from covid itself (or MISC or other complications).

      A secondary benefit it reducing spread. Earlier you mentioned that the vaccines don’t seem to help much, but the paper in this post shows that vaccines at worst prevent 50% of infections (and presumably a transmissions). Plus, other studies have found that even at the same Ct count, vaccinated people have 30% less culture-able virus in their nose. Combined, that seems like a substantial reduction in transmission risk.

      https://www.medrxiv.org/content/10.1101/2021.09.28.21264260v1

      I don’t think it’s my kids’ burden to protect a bunch of unvaccinated adults, but reducing spread has societal benefits that I do promote.

      • samjlord says:

        Also, after reading this study from Israel, I’m actually a little relieved. The worst group (young men) experienced a 13-fold increase in (mostly mild) myocarditis rates, *compared to pre-pandemic rates*. The actual cost/benefit is likely to be better, because (A) returning to pre-pandemic risk levels isn’t possible and (B) I suspect that unhealthy young men were more likely to get vaccinated in the first place, so this data is likely confounded by that.

    • I find it bizarre that the adenovirus vaccines are not being tested in children from what I can tell. At a minimum, why not test those as well as a backup plan, in case the mRNA trials in children go poorly?

      The adenovirus COVID-19 vaccines (J&J, AstraZeneca/Oxford, Sputnik, and maybe a couple others I can’t think of right now) all look like they have some thrombosis problems, particularly in younger women. The risk is not high compared to other risks, but the “pause” of J&J got lots of people scared.

      There may not be an even larger thrombosis problem in kids, especially girls, but then again there may be. I’m not in on the relevant discussions, but I imagine nobody quite has the stomach to face that particular risk if there’s an alternative.

  9. Radu Floricica says:

    Tests may not be completely “free” either:
    https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2779393
    The text is trying to play down the risk, but for young, healthy people it looks to be within an order of magnitude of serious Covid. Add an x20 if they’re tested regularly, and it actually looks pretty bad.

  10. alesziegler says:

    Here is a “what went wrong” interview with Scott Gottlieb and Nate Silver https://www.youtube.com/watch?v=5F-guqZNID4

  11. Laggsu says:

    Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 […] ; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male).

    These numbers don’t really add up.
    Can someone explain why females (3 436k) + males (1637k) is larger (5073k), than the number of individuals (4920k)?

    • David W says:

      I don’t think you’re reading it as the author intended. It should be (4 920 K) people considered for the study. (3 436k) accepted into the study. The accepted people were (1 799k) female and (1 637k) male. The other (1 484 k) people didn’t have data collected because they weren’t eligible for one reason or another, so they can’t say how many were female or male.

  12. Eye Beams are Cool says:

    No Covid, but I took my firsty Wegovy injection last Saturday. I noticed twice that I was pretty full after eating a big meal. But that’s about it. However, I’m just in week 1 when the dose is very low.

    1) Stupid pharma name watch in full effect. I got scolded by a pharamcist when I pronounced it wrong. Fortunantly, they were out of stock (like most pharmacies) and I didn’t have to reward them with my buisness.
    2) My major-name insurnace company started covering it a few weeks ago. Worth checking regularly.
    3) My “weight-loss specialist PCP” (it says so on his wall) had never heard of it. *sigh*. At least he looked into when I asked / suggested I might need to find a new doc if he won’t perscribe it.
    4) I don’t love needles, like at all, but the pen in an engineering marvel and I am very impressed with the UX design.
    5) I’ve lost a lot of weight once, put most of it back on durring COVID, and have lost ~20 lbs since starting daily calorie tracking again. If this take the edge off the hunger on a more regular basis, it will be the greatest thing ever. Thanks to everyone talking about this and bringing it to my attention.
    5b) If you do calorie tracking and weight tracking, you really really need to check out the new app MacroFactor. It does an outstanding job of calculating a weighted body-weight trend the strips the day-to-day water-weight noise out of the signal in your weight change. Then it uses that and your food log to (after ~20 days) produce a (for me) very, very accurate TDEE. It aims to replace the spreadsheet every body-comp conscious person keeps, and it does so for me. I have no relation to MacrFactor or StrongerByScience other than as a consumer.

  13. Sebastian H says:

    More on the gain of function research that may or may not have been going on. I still think lab leak low percentage, but this kind of stuff makes me think I need to revise way upward.

  14. Anon says:

    I think some Bayesians are misunderstanding social commentary. When people express they are shocked by a norm violation or that they expect institutions to follow social norms, they are not just bad Bayesians who naively predict norms will not be violated. They are social commentators trying to defend a social norm.

    “I expect you not to lie to us” is not just a prediction that you will not lie to us, and perhaps no prediction at all. It communicates a social obligation. Why does this matter? Because if those comments are publicly met with ridicule and scorn, that actively damages the social norms they are trying to reinforce. It implies rewarding defectors and punishing cooperators with regards to the norm. So you should do it only to norms you *want* to see destroyed.

    • TheZvi says:

      On the meta-norm level, I would prefer to see a norm of expressing something other than shock when defending the norm, and for norms to be defended in an honest fashion, and to have a norm of doing such things in an honest fashion. But of course, I will not be shocked or surprised when others defend norms, including good norms, in a dishonest fashion.

      If this was one of those rituals where no one believed in the components as non-ritual things, I’d mostly be fine with it, but I don’t think “The CDC should be worthy of our trust” justifies reinforcing trust in the actual CDC if the actual CDC isn’t worthy of it, or of telling people to trust it, etc etc. More ‘level with people, they can handle it.’

      • Anon says:

        I fully agree. But there is a difference between communicating that and just mocking people who are trying to reinforce the norms, as for instance that one “peek a boo” joke on Twitter did when a journalist tried to reinforce a political norm of not lying to the public. Framing matters a lot here: If you are communicating, “We all know that the President can’t be trusted and it’s shameful we have come to this place”, that is perfectly fine. If you are merely shrugging your shoulders, “I’m not surprised, this is the new normal now, so what?” the message may be perceived very differently. There is a whole class of memes trying to do that, e.g. the “Orange Man Bad” meme was not just used to critique unjustified criticisms of the ex-president, but as a fully generalized weapon to mock critics. “Break all the norms as hard as you can and mock everyone who gets upset” may be a good partisan strategy among some circles, but it’s also a good way to destroy norms. Of course, as I said, some norms are worth destroying, but some have a useful function.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s