Fear and Loathing, a Rat Flu Odyssey

[Thaleia]

Vibes about the covid. Butt thats not the real story here.

Are you referring to hiv+ side action guy who lives with them in their garage? Nope, totally nothing else to say there.

EDIT or maybe it was something about moving to the gulf coast between Biloxi and Mobile? Pretty sure there's no hurricane threat down there, right?

[riser4]

Are you referring to hiv+ side action guy who lives with them in their garage? Nope, totally nothing else to say there.

EDIT or maybe it was something about moving to the gulf coast between Biloxi and Mobile? Pretty sure there's no hurricane threat down there, right?

It's worse than I could possibly imagine. Vibes man. Guess you can't choose family. As has been pointed out, at least they got to see some gators.

[jono]

Argument for skipping second doses (for a while, at least):

We used documents submitted to the Food and Drug Administration2 to derive the vaccine efficacy beginning from 2 weeks after the first dose to before the second dose (Table 1). Even before the second dose, BNT162b2 was highly efficacious, with a vaccine efficacy of 92.6%, a finding similar to the first-dose efficacy of 92.1% reported for the mRNA-1273 vaccine (Moderna).3

https://www.nejm.org/doi/full/10.1056/NEJMc2036242

Thoughts? Hopes? Unless this is garbage it seems like a huge leap compared to earlier guesswork about that strategy, no?

[wooley12]

We’re talking about sending our kids back to school or continuing with virtual. That’s a decision we Have to make as parents.

Yeah, but some parents are clueless about covid and should be ignored. Run the play the coach sends in, don't think and weaken the team.

[old goat]

Argument for skipping second doses (for a while, at least):



https://www.nejm.org/doi/full/10.1056/NEJMc2036242

Thoughts? Hopes? Unless this is garbage it seems like a huge leap compared to earlier guesswork about that strategy, no?

The main problem is that the duration of efficacy of the one dose vs two dose regiment is unknown. It is quite possible that efficacy falls considerably after a few months, leaving recipients not only unprotected but unaware of being unprotected. The other issue is whether the second dose leads to antibody levels high enough to be more protective against the South African variant than a single dose.

From the standpoint of the health of the individual recipient a single dose seems like a bad idea, at least until the duration of efficacy can be determined--if it can be determined. From a public health standpoint one could model the overall reduction in cases under various scenarios of single dose efficacy duration compared to the two dose regimen (whose duration is also unknown) and decide whether vaccinating a lot of people with one dose or half the number with two doses prevents more cases. (At this point I think cases is the important statistic. A vaccine that lets people get infected but not die doesn't do much to prevent spread and particularly the emergence of variants. Variants are what we're really fighting now.)

By the time we really know it may be moot--they may be enough vaccine for everyone, but it would still be good to know for when a totally resistant variant or another novel coronavirus emerges.

I read that the moderna dose is 3 times stronger than the pfizer and they are studying whether to decrease the dose to get more doses.

[Catfish]

No, they’re going down which has everyone stoked about how awesome we are. But, case rates and hospitalization numbers are still orders of magnitude higher than even as recently as late summer.

I hear you ugly, but with minimal testing and non existent contact tracing, we’re just making guesses as to the true affect on he community. Also, what are the long term effects on kids? What about the kids with symptoms similar to Kawasaki Syndrome? The chances may be astronomically low, but I’m not comfortable gambling my kids well being on a bunch of probably.

I bet that missing out on school/socialization/milestones while being quarantined and masked will have an infinitely greater negative impact on kids than corona.

[wooley12]

I'll take that bet.

[glademaster]

I'll take that bet.

Me too.

[Catfish]

How much, what odds, what metrics? I’m in for 10K. You guys choose the Mag for escrow.

[jono]

The main problem is that the duration of efficacy of the one dose vs two dose regiment is unknown. It is quite possible that efficacy falls considerably after a few months, leaving recipients not only unprotected but unaware of being unprotected. The other issue is whether the second dose leads to antibody levels high enough to be more protective against the South African variant than a single dose.

From the standpoint of the health of the individual recipient a single dose seems like a bad idea, at least until the duration of efficacy can be determined--if it can be determined. From a public health standpoint one could model the overall reduction in cases under various scenarios of single dose efficacy duration compared to the two dose regimen (whose duration is also unknown) and decide whether vaccinating a lot of people with one dose or half the number with two doses prevents more cases. (At this point I think cases is the important statistic. A vaccine that lets people get infected but not die doesn't do much to prevent spread and particularly the emergence of variants. Variants are what we're really fighting now.)

By the time we really know it may be moot--they may be enough vaccine for everyone, but it would still be good to know for when a totally resistant variant or another novel coronavirus emerges.

I read that the moderna dose is 3 times stronger than the pfizer and they are studying whether to decrease the dose to get more doses.

The whole problem with that line of thought is that we don't know duration of either 1 or 2 dose regimens. So we have no direct evidence that 2 will last longer than 1 or to be confident long term of either approach (except, per Mofro IMS, SARS gave lasting T-cell immunity, so it seems probable).

If immunity continues to rise for 6-8 weeks after a single dose and the level of immunity is very similar to two doses after a couple of months then the public health case is overwhelming: if we can vaccinate 200% more people by giving up 1% efficacy we shouldn't need a calculator or a napkin to see which way is better.

I haven't gone through their details much yet, but if all we have to look at are 1 or 2 week chunks of time and efficacy goes from ~60 to 92 and then 95 across those steps it stands to reason that more granular data would probably show a continual rise. There just isn't much room between 92 and 95 for that second dose to being doing much of anything to it. Hell, if efficacy peaked at 92 (which is virtually impossible if that's the average of a 2 week block of time that starts lower) the relative difference is still just 3%--for double the doses!

At some point we have to recognize that the "risk" of playing it safe is not a risk, it's a certainty of some number of deaths. I'm all for following the science, but waiting for better data has a cost both in lives and mutation risk. Find a way to contain the risk if we're wrong and move forward with the best guess as to what's optimum. Fauci has been saying no to this, but the conventional wisdom finally came around on aerosols, and if the analysis on this is good it should create some pressure. Fast.

[bigdude2468]

[QUOTE=old goat;6239140]Who says we have no problem. Why do you think there are fewer and fewer places where people can smoke in public--in CA basically no where. To the extent that people are still dying from second hand smoke it's from smoking at home. My dad smoked and died from it. I've had a heart bypass, my brother a heart attack at 35. Second hand smoke, bad genes, bad diet, all of the above?

It's been well established by the courts that govts have the right to prevent people from spreading dangerous infectious diseases to others, by quarantining them, confining them if uncooperative etc. It's also been well established that parents don't have unlimited control over their children. We can prevent them from beating and raping them of course, but also prevent them from withholding medical care in the cases of Christian Scientists and from withholding blood transfusions in the case of Jehovah's Witnesses. Adults have the right to withhold those things from themselves but not from their children if a court determines they are necessary.

Courts change and given the current makeup of the SCOTUS it wouldn't shock me if the govt's right to impose public health measures is overturned, but for now it is the law.[/QUOT

I was in no way making a comparison between tobacco deaths and covid deaths to diminish covid. We have a deadly drug (cigarettes) that kills 450,000 people every year and we make it just inconvenient for people to us it. I think its hypocritical for Govt. to tell us how bad cigarettes are but if you want to smoke we will add $5 a pack to the cost and that makes it ok.

Yesterday during the hearings on Robinhood / Redditt / Gamestop there is outrage how the little guy get hurts, Wall Street is rigged and we need to do something about it. At the same time state governments have no problem collecting billions in lottery ticket proceeds that return about .40 for every $1 they collect.

[MTT]

[Bunion 2020]

I think its hypocritical for Govt. to tell us how bad cigarettes are but if you want to smoke we will add $5 a pack to the cost and that makes it ok.

Holy shit that is funny.

[Kinnikinnick]

I bet that missing out on school/socialization/milestones while being quarantined and masked will have an infinitely greater negative impact on kids than corona.

So “infinitely?”

In other words every single one will kill themselves or go crazy and murder people.

Cause you know infinitely is the biggest mathematical statement possible.

I’ll act as the bet arbiter. Since that will be literallu impossible to “have an infinitely greater negative impact”, catfish owes $10k.

Pay up, pm me for the paypal address. I’ll distribute equally among thread participants.


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[riser4]

The limit of credibility as stupidity goes to infinity.

[Bunion 2020]

So “infinitely?”

In other words every single one will kill themselves or go crazy and murder people.

Cause you know infinitely is the biggest mathematical statement possible.

Give him a break, the Football Coach is usually the Shop Teacher and not expected to exhibit the mastery of advanced mathematics.

[jono]

I haven't gone through their details much yet,

I should have just read the NEJM letter's chart slower, the details are straightforward. The sample size was kind of small to get very precise about efficacy numbers for the single week before the second shot but the 95% confidence interval is 69-98.3%, so not a negligible result.

And it lines up well with the 85% efficacy just found in Israel between days 15-28, considering that the Sheba study defined positive as any infection detected and the HCWs studied were tested daily. That's not apples to apples: in some ways the Sheba study seems like better news at 85% than 92% prevention of symptomatic COVID-19.

https://www.thelancet.com/journals/l...448-7/fulltext

[OphirPow]

Zzsz


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[CarlMega]

Give him a break, the Football Coach is usually the Shop Teacher and not expected to exhibit the mastery of advanced mathematics.

I'm willing to wager on his ability to solicit 10 large. The trailer home would have to be in hock.

[old goat]

The whole problem with that line of thought is that we don't know duration of either 1 or 2 dose regimens. So we have no direct evidence that 2 will last longer than 1 or to be confident long term of either approach (except, per Mofro IMS, SARS gave lasting T-cell immunity, so it seems probable).

If immunity continues to rise for 6-8 weeks after a single dose and the level of immunity is very similar to two doses after a couple of months then the public health case is overwhelming: if we can vaccinate 200% more people by giving up 1% efficacy we shouldn't need a calculator or a napkin to see which way is better.

I haven't gone through their details much yet, but if all we have to look at are 1 or 2 week chunks of time and efficacy goes from ~60 to 92 and then 95 across those steps it stands to reason that more granular data would probably show a continual rise. There just isn't much room between 92 and 95 for that second dose to being doing much of anything to it. Hell, if efficacy peaked at 92 (which is virtually impossible if that's the average of a 2 week block of time that starts lower) the relative difference is still just 3%--for double the doses!

At some point we have to recognize that the "risk" of playing it safe is not a risk, it's a certainty of some number of deaths. I'm all for following the science, but waiting for better data has a cost both in lives and mutation risk. Find a way to contain the risk if we're wrong and move forward with the best guess as to what's optimum. Fauci has been saying no to this, but the conventional wisdom finally came around on aerosols, and if the analysis on this is good it should create some pressure. Fast.

Good point that we don't know the duration for either regimen. The difference being that for the 2 dose Phase 3 recipients I'm assuming they will be followed out, hopefully for at least a few years. If someone is going to run a trial on a 1 dose regimen they'd better hurry because once vaccine is widely available no one will volunteer. The only way we will know that immunity is gone is when people start getting sick. We do know from studies of multiple vaccines that 2 or 3 doses provides better and longer lasting immunity than 1.

The strongest argument I can make for the 2 dose regimen is hypothetical--if 2 doses gives significantly better protection against variants--the S African or variants yet to be identified--then giving 1 dose gives a big selection advantage to the variants and pretty soon resistant variants are all we have. From a population standpoint a single dose regimen may still be best. I'm just laying out the arguments against the single dose; I'm not remotely qualified to take sides.

One other practical benefit for the 2 dose regimen at 3-4 weeks: if the idea is to eventually give 2 doses, the sooner the second dose is given the greater the likelihood that people will get it. If you start going out to months a lot of people are not going to show up.

If you have MD after your name (or DO--my DIL is in osteopathic school) your training is to think about the benefit to the individual patient over the benefit to society as a whole. You are trained to let someone else worry about that. Dr. Fauci has an MD after his name; no matter how long it has been since he treated a patient (other than his family [shudder]) the earliest training lasts the longest. So Fauci might not be the best person to be making the call, at least not solo.

Give him a break, the Football Coach is usually the Shop Teacher and not expected to exhibit the mastery of advanced mathematics.

Whoa! My shop teacher is the only one I remember from junior high. Frederick T. (I hate stupid questions) Grigsby, who wiped your nose with your varnish brush to see if you cleaned it well. A man with standards who didn't tolerate shabby work and who, as someone forced to earn his living using Imperial measurements, had mastered mathematics, at least as far as fractions. I still use my JHS shop apron.

[jono]

I don't know if we'll see a study on single doses here, but the ones in Israel (Lancet link above) and the UK (bumping second doses to 12+ weeks on everyone) should be of some use if we're paying attention. I think the odds favor the UK deciding to stick with a single dose unless supply is massively higher by then.

Obviously I'm not qualified in any way, I'm just looking at the math. In my field we have a strong bias against taking risks by trying things we haven't fully validated ahead of time. But we generally have the luxury of designing things that don't have to exist. When that changes (like in military or emergency applications where risk is inherent) the level of risk has to change with it, as uncomfortable as that is for those of us that like to stay well within established envelopes. So...good point about Fauci.

[old goat]

I agree that in the current situation we don't have the luxury of not taking any risks. The biggest risk is making certain. I certainly hope that when they redesign mRNA boosters for variants they do minimal testing. We're in a race against the clock.

Personally I'm planning to wait an extra week at least for the second moderna dose--I have a (fully vaccinated) son coming to ski the week I'm supposed to get it.

[MultiVerse]

If you have MD after your name (or DO--my DIL is in osteopathic school) your training is to think about the benefit to the individual patient over the benefit to society as a whole. You are trained to let someone else worry about that. Dr. Fauci has an MD after his name; no matter how long it has been since he treated a patient (other than his family [shudder]) the earliest training lasts the longest. So Fauci might not be the best person to be making the call, at least not solo.

The medical profession is more concerned with errors of commission than they are errors of omission. For a bunch of behavioral reasons failing to act is not perceived to be as bad as taking an action that subsequently causes some harm.

As Jono mentioned it's not just the medical profession. Studies show politicians are rewarded by voters for their response to a disaster not for preparedness and prevention. Politicians get credit for multi trillion dollar relief packages, not for spending a few tens of billions more on vaccines.

That's why for political economy / public choice reasons I don't think Dr. Anthony Fauci is much of a factor in any of this. Fauci has a marginal impact but his game involves flattering the right people, making the right political argument. It's not necessarily about the science. The reality is a person can either be ethically pure or be useful but not both. Fauci is better than most. As long as the American people are not demanding more vaccine from their politicians then Fauci and the rest of the bureaucratic apparatus are forced to compromise between doing the optimal thing, the right thing, and not getting crushed by their political bosses.

That's a harder problem than identifying the best course of action which is: first-dose-first. That's why random people on a message board can appear smarter than the pros. Because the math is straightforward, not pursuing a first-dose-first strategy will cause more death and suffering than a strict two dose strategy. The pros, however, are trying to solve a harder problem complicated by politics.

[jono]

For sure. Conversely, the randos on a message board are a little more like the general (no to say exactly "voting") public.

Interesting point about Fauci again--his ability to stay on the fences with the politicians may be less valuable these days than it was last year.

[MTT]