Re Caplan, libertarians, and Permanent Midnight: I mostly agree. But re this:
> I also don’t expect a Permanent Midnight scenario to take hold so easily. There is a reason China eventually gave up. The cost of maintaining these kinds of restrictions rises with time, and anyone calling for them to be sustained will get voted out, and I expect people patience to if anything be lower next time.
What gives me pause is other scenarios where it has taken hold: TSA post-9/11, for example. Or the thing where you can only get Sudafed at a pharmacy (in some states, only *with a prescription*).
> As I’ve noted, wastewater and hospitalizations are useful while having their own problems.
Have you talked about this in more detail anywhere? Interested in your thoughts on wastewater monitoring in particular. Seems it could (if calibrated against historical case counts) give a good signal for short-term regional-level risk if it can be calibrated consistently, in a way that test positivity is less and less capable of doing. (Eventually the number of tests will be extremely low; when does it break entirely? Doe we expect hospitals to forever test for Covid and therefore have some stable base of comparison?)
Another benefit of rapid tests: they enabled telemedicine providers to prescribe Paxlovid. I think technically doctors could still prescribe based on an assessment of symptoms. But requiring a photo of a positive test, which may not even belong to the patient, probably gave them more confidence that the authorities wouldn’t come after them for enabling line skippers.
I took advantage of this when my mother-in-law was sick. Local doctors wanted patients to come in for a PCR. Not only was this a bad idea to disrupt her bed rest, it could have spread the disease further.
re: "It is also all but certain that you and the agency you head, sir, are the reason we don’t have a more effective updated booster on the way sooner. It is on you that by the time we get a booster that works it will be too late to do much good."
What do we think is the best way to get the question "if we can target new vaccines within a matter of days, so why don't we have one for [insert latest variant here] now?" asked by major media outlets?
If that works, sure, I'll take it! But I'm serious, we should find out, and do it. Just in the past 2 days I've seen in-depth reporting from 60 Minutes about Which Dirty Foreigners Paul Ehrlich Wishes Would Die and minute by minute reporting on 6 (7? 8?) completely pointless speaker elections, but "new omicron variant + we can literally make new targeted boosters + FDA officials bemoan people thinking vaccines are useless + FDA officials making vaccines more useless" doesn't get a blip? Maybe "Democracy Dies in Darkness", but I bet "Marginally More People Non-Metaphorically Die of Diseases They Wish They Had Vaccines For" too. What's even the point of a news media - any of it! - if this isn't on the menu?
If genetics isn't the biggest factor in obesity (at least in the modern, US environment), how do you explain that huge gap in correlation of obesity between monozygotic vs. dizygotic twins? The correlation jumps from 0.4 for dizygotic to over 0.8 in monozygotic. I was skeptical of the claim that obesity = mostly genetics, but that stat is pretty damning for any other conclusion.
I don't have the expertise and haven't put in the time to try to reconcile that particular stat with the argument of Venk Murthy, but I'd be happy to read any synthesis of that information.
Dr Murthy just shows he chooses to understand neither PGSes nor heritability with that tweet's first point. It's not an interesting or subtle error. PGses are a *lower bound* on variance explained by genetic influences, because they are only the specific variants estimated thus far; the relevant number is the total variance explained by genetic influences, ie. 'heritability'. This is a surprisingly common error in the GWAS era, but this instance is particularly striking because he *acknowledges that they change and increase over time* by using the word 'best' - however, you can't really argue that PGSes = total genetic influence and also acknowledge that PGSes increase over time (as larger sample sizes make them more effective): does he really think that genetics had zero causal influence on obesity 10 years ago when the 'best PGS' was ~0%? Or that the causal influence suddenly jumps instantaneously across the entire population when a new BMI PGS study is published tomorrow bumping it +1%?
I think what goes on here is the 'no evidence for' fallacy combined with the typical SSSM of blank-slatism: "there is 'no evidence' for >10% PGS (yet), therefore, it must be 90% environmental" (and then quietly leave out or forget heritability, knowing the popular audience this is aimed at has no idea about heritability or has been FUDed into ignoring it).
The right response, of course, is to bring up heritability being within-environment and talk about how the whole environment has shifted in 'obesogenic' directions so the whole population shifts towards obesity even if genetic factors continue to be the most powerful influence on where one winds up within that fatter population, and the concept of reaction norms; but alas, that doesn't give you the pithy fallacious 'genetics is only 10% of obesity because PGS!' talking point for Twitter.
Your first sentence is wrong and non-responsive to what I already said.
And the second is a non sequitur: you may not like genetics being the primary driver of individual differences within the current environment because it is evidence that standard interventions within the usual range of interventions are ineffective (and they are), but what you like has no bearing on reality; if you believe correct things about reality, you are in a better position to understand how obesity really works and how it does not drop out of the sky with no prior causes besides McDonald's advertising or myths about 'food deserts', and is mediated through things like exercise nonresponse and enslavement to hormonal appetite regulation and homeostasis, and why you should place a lot more hope in, say, subsidizing semaglutide use rather than $CURRENT_FIRST_LADY exhorting schoolchildren to get off the couch (again).
The problem is we also don't know what exactly it is about modern environment and society that has resulted in increased obesity, so it's not like we can just reset the culture to 40 years ago. By all means, society should continue to promote healthy lifestyles and publicize the unhealthy outcomes of obesity, but it's pretty clear that approach isn't effective in reducing obesity rates.
Any thoughts on Nitric Oxide Nasal Spray such as Enovid/SaNOtize? It seems to help a little for people who are mildly symptomatic (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239922/), and I would imagine it would help if taken prophylactically after a potential exposure but I couldn't find any data that directly addresses that.
> It seems plausible, for example, based on the details we know, that a given Omicron case could generate a larger wastewater signature than a pre-Omicron case. I’ve seen no attempts to measure this and find out. I haven’t talked about that concern.
and
> I agree that there is danger when comparing case numbers now to case numbers a year ago. I still think that comparing to last week is highly useful, as the reporting regime will have changed little. Thus, I still see them as useful, as long as they are combined with a metric that does not have this problem, such as deaths.
You correctly point out that week-over-week we should expect little change in testing prevalence, so it's a useful metric. But you don't apply the same heuristic to wastewater prevalence, even though week-over-week data should be useful there as well, even if different variants produce different amounts of virus in people's waste.
Re: "He cites this paper as important, emphasizing the roll of county-level political affiliation and its correlation to excess deaths, and that state governments that enforced their restrictions narrowed these gaps."
I am skeptical of this for a couple of reasons. First, none of the authors appear to be actuaries. Doing this kind of analysis on the data without an actuary is like doing an audit without a CPA. Second, past studies of this kind of data don't account for factors that actuaries have known about for years - income and urban/rural are very, very highly correlated with poor health outcomes.
A friend has a substack where she does deep dives into the US death certificate data from the CDC and discusses the results. She is a very respected actuary and her professional work is used to make very significant financial decisions by her employer. She has looked at similar studies done in the past and disputed their conclusions.
Informative as always -- thanks. One thing I didn't see covered: Iwasaki is concerned that Long COVID could be worse with XBB.1.5 because of increased tropism in long-lived cells, citing Cao's research showing much higher hACE2 binding affinity. Haven't seen much additional discussion on this point. https://twitter.com/VirusesImmunity/status/1610032727406874627
With regards to MAID, I feel like the eligibility is so broad basically anyone can apply for and receive it, and that the government has an incentive to do so because it's cheaper to just have someone die than to actually provide healthcare to them (especially in a public healthcare system like Canada has).
The problem, of course, is that as a general rule, society has a social norm against encouraging suicide, and the social norm that this is a good social norm to have no matter how much you might want to argue against it and make e.g. the "yay personal liberty" argument. There's a reason it's frowned upon to yell "kill yourself" at others on the internet, even and especially if the other person might be willing to do so. However, MAID seems to have worked around this norm through a backdoor where they slowly expanded the amount of people eligible for the program, from people who were doomed to die anyway that "suicide" is meaningless to apply to them, to people who are not in any way doomed to die but have severe mental health problems that make them routinely consider suicide.
Regardless of whether one may agree or disagree about the general social norm against encouraging suicide, it's a clear problem that MAID has simply ignored it without so much as a conversation about the implications of doing so.
Missed opportunity to title this "Variant XBB Takes". Appreciated update though. Even at a low worry threshold, it's still a relief to see this will very likely not, in fact, be remotely like last winter. (Although extra flu/RSV/colds replicate many of the same annoyances - I'd rather coworkers have those than covid, but sick calls are sick calls either way, and they're pervasive once again.)
Every time noises start getting made again about potential mask mandates, I get fearful flashbacks to when those last existed locally; that was a deeply miserable time as a masks-are-nontrivial-for-me individual. So it's good to know surgical masks are a little less useless than previously thought - this updates towards potential mandates being like last time, e.g. not requiring N95 or KN94 or whatever. And that's good - the possibility of complying via worse masks makes the difference for me between "will reluctantly leave house" and "not show up to most things at all, live off savings for awhile". Which I guess is Feature Not Bug anyway, that's certainly one way to suppress spread...but the profit/pain ratio is so much worse.
Re Caplan, libertarians, and Permanent Midnight: I mostly agree. But re this:
> I also don’t expect a Permanent Midnight scenario to take hold so easily. There is a reason China eventually gave up. The cost of maintaining these kinds of restrictions rises with time, and anyone calling for them to be sustained will get voted out, and I expect people patience to if anything be lower next time.
What gives me pause is other scenarios where it has taken hold: TSA post-9/11, for example. Or the thing where you can only get Sudafed at a pharmacy (in some states, only *with a prescription*).
> As I’ve noted, wastewater and hospitalizations are useful while having their own problems.
Have you talked about this in more detail anywhere? Interested in your thoughts on wastewater monitoring in particular. Seems it could (if calibrated against historical case counts) give a good signal for short-term regional-level risk if it can be calibrated consistently, in a way that test positivity is less and less capable of doing. (Eventually the number of tests will be extremely low; when does it break entirely? Doe we expect hospitals to forever test for Covid and therefore have some stable base of comparison?)
Another benefit of rapid tests: they enabled telemedicine providers to prescribe Paxlovid. I think technically doctors could still prescribe based on an assessment of symptoms. But requiring a photo of a positive test, which may not even belong to the patient, probably gave them more confidence that the authorities wouldn’t come after them for enabling line skippers.
I took advantage of this when my mother-in-law was sick. Local doctors wanted patients to come in for a PCR. Not only was this a bad idea to disrupt her bed rest, it could have spread the disease further.
re: "It is also all but certain that you and the agency you head, sir, are the reason we don’t have a more effective updated booster on the way sooner. It is on you that by the time we get a booster that works it will be too late to do much good."
What do we think is the best way to get the question "if we can target new vaccines within a matter of days, so why don't we have one for [insert latest variant here] now?" asked by major media outlets?
If that works, sure, I'll take it! But I'm serious, we should find out, and do it. Just in the past 2 days I've seen in-depth reporting from 60 Minutes about Which Dirty Foreigners Paul Ehrlich Wishes Would Die and minute by minute reporting on 6 (7? 8?) completely pointless speaker elections, but "new omicron variant + we can literally make new targeted boosters + FDA officials bemoan people thinking vaccines are useless + FDA officials making vaccines more useless" doesn't get a blip? Maybe "Democracy Dies in Darkness", but I bet "Marginally More People Non-Metaphorically Die of Diseases They Wish They Had Vaccines For" too. What's even the point of a news media - any of it! - if this isn't on the menu?
If genetics isn't the biggest factor in obesity (at least in the modern, US environment), how do you explain that huge gap in correlation of obesity between monozygotic vs. dizygotic twins? The correlation jumps from 0.4 for dizygotic to over 0.8 in monozygotic. I was skeptical of the claim that obesity = mostly genetics, but that stat is pretty damning for any other conclusion.
I don't have the expertise and haven't put in the time to try to reconcile that particular stat with the argument of Venk Murthy, but I'd be happy to read any synthesis of that information.
Source: https://www.nature.com/articles/s41539-017-0005-6, figure 1 (which I saw at https://slatestarcodex.com/2017/04/25/book-review-the-hungry-brain/).
Dr Murthy just shows he chooses to understand neither PGSes nor heritability with that tweet's first point. It's not an interesting or subtle error. PGses are a *lower bound* on variance explained by genetic influences, because they are only the specific variants estimated thus far; the relevant number is the total variance explained by genetic influences, ie. 'heritability'. This is a surprisingly common error in the GWAS era, but this instance is particularly striking because he *acknowledges that they change and increase over time* by using the word 'best' - however, you can't really argue that PGSes = total genetic influence and also acknowledge that PGSes increase over time (as larger sample sizes make them more effective): does he really think that genetics had zero causal influence on obesity 10 years ago when the 'best PGS' was ~0%? Or that the causal influence suddenly jumps instantaneously across the entire population when a new BMI PGS study is published tomorrow bumping it +1%?
I think what goes on here is the 'no evidence for' fallacy combined with the typical SSSM of blank-slatism: "there is 'no evidence' for >10% PGS (yet), therefore, it must be 90% environmental" (and then quietly leave out or forget heritability, knowing the popular audience this is aimed at has no idea about heritability or has been FUDed into ignoring it).
The right response, of course, is to bring up heritability being within-environment and talk about how the whole environment has shifted in 'obesogenic' directions so the whole population shifts towards obesity even if genetic factors continue to be the most powerful influence on where one winds up within that fatter population, and the concept of reaction norms; but alas, that doesn't give you the pithy fallacious 'genetics is only 10% of obesity because PGS!' talking point for Twitter.
Your first sentence is wrong and non-responsive to what I already said.
And the second is a non sequitur: you may not like genetics being the primary driver of individual differences within the current environment because it is evidence that standard interventions within the usual range of interventions are ineffective (and they are), but what you like has no bearing on reality; if you believe correct things about reality, you are in a better position to understand how obesity really works and how it does not drop out of the sky with no prior causes besides McDonald's advertising or myths about 'food deserts', and is mediated through things like exercise nonresponse and enslavement to hormonal appetite regulation and homeostasis, and why you should place a lot more hope in, say, subsidizing semaglutide use rather than $CURRENT_FIRST_LADY exhorting schoolchildren to get off the couch (again).
The problem is we also don't know what exactly it is about modern environment and society that has resulted in increased obesity, so it's not like we can just reset the culture to 40 years ago. By all means, society should continue to promote healthy lifestyles and publicize the unhealthy outcomes of obesity, but it's pretty clear that approach isn't effective in reducing obesity rates.
Any thoughts on Nitric Oxide Nasal Spray such as Enovid/SaNOtize? It seems to help a little for people who are mildly symptomatic (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239922/), and I would imagine it would help if taken prophylactically after a potential exposure but I couldn't find any data that directly addresses that.
I notice a bit of a disconnect between:
> It seems plausible, for example, based on the details we know, that a given Omicron case could generate a larger wastewater signature than a pre-Omicron case. I’ve seen no attempts to measure this and find out. I haven’t talked about that concern.
and
> I agree that there is danger when comparing case numbers now to case numbers a year ago. I still think that comparing to last week is highly useful, as the reporting regime will have changed little. Thus, I still see them as useful, as long as they are combined with a metric that does not have this problem, such as deaths.
You correctly point out that week-over-week we should expect little change in testing prevalence, so it's a useful metric. But you don't apply the same heuristic to wastewater prevalence, even though week-over-week data should be useful there as well, even if different variants produce different amounts of virus in people's waste.
Re: "He cites this paper as important, emphasizing the roll of county-level political affiliation and its correlation to excess deaths, and that state governments that enforced their restrictions narrowed these gaps."
I am skeptical of this for a couple of reasons. First, none of the authors appear to be actuaries. Doing this kind of analysis on the data without an actuary is like doing an audit without a CPA. Second, past studies of this kind of data don't account for factors that actuaries have known about for years - income and urban/rural are very, very highly correlated with poor health outcomes.
A friend has a substack where she does deep dives into the US death certificate data from the CDC and discusses the results. She is a very respected actuary and her professional work is used to make very significant financial decisions by her employer. She has looked at similar studies done in the past and disputed their conclusions.
https://marypatcampbell.substack.com/
Informative as always -- thanks. One thing I didn't see covered: Iwasaki is concerned that Long COVID could be worse with XBB.1.5 because of increased tropism in long-lived cells, citing Cao's research showing much higher hACE2 binding affinity. Haven't seen much additional discussion on this point. https://twitter.com/VirusesImmunity/status/1610032727406874627
With regards to MAID, I feel like the eligibility is so broad basically anyone can apply for and receive it, and that the government has an incentive to do so because it's cheaper to just have someone die than to actually provide healthcare to them (especially in a public healthcare system like Canada has).
The problem, of course, is that as a general rule, society has a social norm against encouraging suicide, and the social norm that this is a good social norm to have no matter how much you might want to argue against it and make e.g. the "yay personal liberty" argument. There's a reason it's frowned upon to yell "kill yourself" at others on the internet, even and especially if the other person might be willing to do so. However, MAID seems to have worked around this norm through a backdoor where they slowly expanded the amount of people eligible for the program, from people who were doomed to die anyway that "suicide" is meaningless to apply to them, to people who are not in any way doomed to die but have severe mental health problems that make them routinely consider suicide.
Regardless of whether one may agree or disagree about the general social norm against encouraging suicide, it's a clear problem that MAID has simply ignored it without so much as a conversation about the implications of doing so.
Missed opportunity to title this "Variant XBB Takes". Appreciated update though. Even at a low worry threshold, it's still a relief to see this will very likely not, in fact, be remotely like last winter. (Although extra flu/RSV/colds replicate many of the same annoyances - I'd rather coworkers have those than covid, but sick calls are sick calls either way, and they're pervasive once again.)
Every time noises start getting made again about potential mask mandates, I get fearful flashbacks to when those last existed locally; that was a deeply miserable time as a masks-are-nontrivial-for-me individual. So it's good to know surgical masks are a little less useless than previously thought - this updates towards potential mandates being like last time, e.g. not requiring N95 or KN94 or whatever. And that's good - the possibility of complying via worse masks makes the difference for me between "will reluctantly leave house" and "not show up to most things at all, live off savings for awhile". Which I guess is Feature Not Bug anyway, that's certainly one way to suppress spread...but the profit/pain ratio is so much worse.