COVID-19: Chapter 10 - Mission Achomlished!

[Yuv]

Fwiw my “bickering” is the dismissal by wookie as a study with such an absurd methodology flaw that it shouldn’t even be considered.

It takes too much trust to imagine this isn’t related to the person who linked the paper. I’m just not a trusting person.

[MrWookie]

https://twitter.com/gadboit/status/1537008982975447041

https://twitter.com/profamirattaran/status/1537112628723580929

A couple. It’s not that easy to find measured criticisms, because the paper’s being weaponized by anti-vaxxers (vaccines weaken your immunity!) and anti-anti-vaxxers (no herd immunity! Omicron won’t protect you from further infection but the vaccines can!) in ways that aren’t supported in the paper, and there are a lot of people misreading it in the same way Trolly did.

[MrWookie]

I have a Ph. D., and you were definitely trolling.

[Yuv]

We all know you have a phd. It has nothing to do with the slight jab i wrote about your first year grad student training comment. You guys cant shit on everyone and have that thin skin, ffs.

[MrWookie]

@Yuv

You guys cant shit on everyone

lol, projection ain’t just a river in Egypt.

[Yuv]

Which is why i dont say every snarky remark is a troll we must stop and debate. Jesus christ.

[Trolly]

@Yuv

Fwiw my “bickering” is the dismissal by wookie as a study with such an absurd methodology flaw that it shouldn’t even be considered.

Maybe this is a language thing here, but Wookie put together a rather lengthy post on why he thought the finding was wrong. That’s hardly a dismissal without consideration. Certainly he could be wrong, but he’s mounted a defensible claim. At least I’d like to see a counter argument beyond a lame argument from authority.

[MrWookie]

If you want to see a much better study, here’s one:

https://www.nejm.org/doi/full/10.1056/NEJMoa2203965?query=featured_home

They enroll thousands of people in carefully matched cohorts and compare clinical outcomes, not just in vitro immune responses.

They find:

No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine–Qatar and others.)

I don’t think they make any distinction about what wave the previous infection was in the people they regard as having had a prior infection, which makes you wonder if they’re missing some strain, temporal, or ordering (getting infected before or after vaccination, e.g.) effects.

[KSR]

I was hoping all the traffic was info about the vaccine for little kids. I was wrong… Anyways once fully approved I’m trying to figure the differences and which would be better, Moderna or Pfizer? If you get Moderna are they just going to get a booster a couple months later? That’s what it seems like Pfizer is basically doing.

[MrWookie]

I’m leaning Moderna, and if you fear the virus more than vaccine side effects, that’s how I’d tell you to lean, too. Moderna’s effectiveness data were not super strong, but at least they had something resembling a decent sample size. Pfizer’s was lol, but they were more concerned with proving the safety of the vaccine for young kids than showing the effectiveness of the vaccine.

[anon38180840]

@Yuv

You are starting to look a bit unhinged there sir

That sure seems like a personal attack. How do I collect my $1M?

[JonnyA]

Just got home from picking up daughter and seems like my request went unheeded. Need to review the last hour of posting, but bans probably incoming and will probable move the bickering to its own derail thread.

[MrWookie]

We looked at some in the early days of omicron, but I’m not finding it right now.

[ChrisV]

Seems like the big question here is whether an Omicron-specific vaccine would generate better lasting protection in totally vaccine- and COVID-naive people.

[Coasterbrad]

Came here to get updates on vaccine approval for kids. Guess we have better things to discuss though.

[MrWookie]

Cliffs:

@MrWookie

So, the efficacy numbers for 2 doses of Moderna in the 2-5 cohort are not terribly impressive:

They’re quite a bit better for 6-12, preventing about twice as many cases.

Apparently no kids in any group got serious covid, which is ultimately a good thing, but it makes it hard to evaluate how much protection is conferred against the small but nonzero chance kids end up in the hospital with covid.

@MrWookie

Pfizer’s data are out: https://www.fda.gov/media/159195/download

And, uh,

Pfizer, your sample sizes, woof!

@CaffeineNeeded

yeah moderna sure looks better.

although weirdly apparently ped vaccine data is usually based more on antibody levels according to a few people i’ve talked to.

@spidercrab

As I understand it, this has been a known (and intentional) difference between Pfizer and Moderna - where exactly they want to land on the tradeoff between efficacy and adverse reactions.

Pfizer’s choice has been to limit adverse reactions, which necessarily means a relatively weaker drug (dosage?). I view this as Pfizer wanting to just clear the minimum threshold of efficacy in order to minimize adverse reactions.

In contrast, Moderna tilts the other way, aiming for the highest possible efficacy while just clearing the threshold for acceptable adverse reactions.

(I am a dork, so I analogize this to the continuum of portfolio investing: do you maximize returns subject to a constrained maximum level of risk, or do you minimize risk subject to a constrained minimum level of expected return?)

So if you’re evaluating Pfizer vs. Moderna, I think Moderna is always going to look better on efficacy. What should be true is that Pfizer should have demonstrably lower adverse events.

If I had a kid in this age range, I’d be getting them vaccinated as fast as I could, and would take either Pfizer or Moderna. But given this fairly ambiguous data, I can also understand parents who are more hesitant.

@CaffeineNeeded

100% agree. I think the difference long term will be quite small, especially in absolute terms too

@MrWookie

I’m leaning Moderna, and if you fear the virus more than vaccine side effects, that’s how I’d tell you to lean, too. Moderna’s effectiveness data were not super strong, but at least they had something resembling a decent sample size. Pfizer’s was lol, but they were more concerned with proving the safety of the vaccine for young kids than showing the effectiveness of the vaccine.

[Danspartan]

Science is not absolute. Every piece of research builds on its predecessors by affirming or contradicting them.

What drives me nuts is when papers have obvious limitations but the authors don’t address them (like sample size or making huge claims contradicting the basic understanding of the subject without highly substantial and significant evidence).

Just because someone points out flaws doesn’t mean the conclusions are wrong. It does mean that one shouldn’t give the conclusions as much weight and perhaps should look for further evidence for or against the conclusion (likely a new paper).

Given the Covid timeline, it’s perfectly understandable that things get through that maybe would get caught in a more deliberative timeline. Things get through that are clearly poor science/analysis but then Covid crises makes it more likely than is normal.

At its best science is done in the spirit of discovery and someone pointing out errors or contradicting evidence is THE valuable part of the entire enterprise. A good scientist welcomes challenges since the objective is increase understanding and utility of the information.

By making any of this personal, this discussion completely misses the point. Wookie was just simply doing the role of a critical reader. Nothing more, nothing less. But the role IS what defines “science”.

[MrWookie]

Fucking @BestOf. I owe you a fermented beverage that meets your precise specifications.

[ChrisV]

Personally I think the case for vaccinating 2-5 year olds is looking a bit questionable. The Science paper requires more research to confirm its results, but it seems like it matches real-world observations about reinfections. The danger of COVID to that age group is very low just going on pure numbers and even lower considering that many children with bad outcomes have pre-existing conditions. The effectiveness numbers are not hugely impressive. Adverse events are possible.

Assuming the basic conclusions of the Science paper are accurate, I don’t think we know yet whether vaccination with an Omicron-specific vaccine or Omicron infection (in completely COVID- and vaccine-naive individuals) results in more robust immune responses to later Omicron infection (correct me if I’m wrong). It may be that Omicron is just good at limiting immune response, period. If I were a parent of a 2-5 year old though, I would not be thrilled about rolling the dice on giving them a lifetime of inferior immune responses, given the fairly modest benefits of vaccination at their age. Essentially the possibility of imprinting is an adverse effect which is not being screened for at all in the trials. We have no clue at all if this is a minor problem or a serious problem.

There’s a piece here from a few days ago making this argument:

Lessons from earlier pandemics: Vaccine panel must discuss imprinting among...

If anyone has commentary on this from anyone who knows what they’re talking about, I’d be interested.

[MrWookie]

1. The Science paper is far from conclusive. Between the small sample sizes, the quesionable nature of the numerous measured zeros, and the inherent disconnect between in vitro proxies and the in vivo results we care about, there are a ton of questions here.
2. Even if we take the results of this paper as gospel, it’s not evidence against vaccination! It’s evidence against catching ancestral Wuhan only. The strongest immune response was from the samples taken from people with 3 shots (which were against the Wuhan strain) and an omicron infection. Naturally, catching omicron is a bad way to avoid catching omicron.
3. This is the only paper I’m aware of that makes a distinction between patients with exactly two past infections of two particular strains and patients with at least one infection of any strain. But, there’s no paper I’m aware of that shows something like a single infection of a post-Wuhan strain is more effective than 3 shots at preventing infection from a subsequent strain. Past work has shown generally that one exposure (whether shot or infection) is better than two is better than three. In fact, the previous Science paper from the lab behind this recent controversial Science paper said that 3 exposures was where the protection maxed out, but this work from the same lab shows that is false, that 3 shots plus an omicron infection was more effective than 3 shots alone (again, I think this study should be taken cautiously, but it’s interesting that they provided evidence against their own prior conclusion based on the same sort of methodology (although the prior work had larger sample sizes, by a factor of 2-4)).
4. I don’t think we have very good temporal resolution of covid immune response. We know it fades with time, but even that hasn’t been easy to untangle from the effects of covid mutation. But, to the extent that imprinting is a thing, how long does that persist? I would hypothesize that it would fade, too, but I’m not sure on what sort of time scale. There’s not evidence that any sort of imprinting effect would last for a lifetime, but we do know that vaccines against Wuhan offer protection against omicron (when boosted recently), especially against the worst outcomes. That last thing is a big deal, and in my opinion, getting robust protection against the worst outcomes now is better than holding out and risking those outcomes for what could be months in the hope of more robust protection against minor infections.