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Brock's avatar

In further news on my participation in the Pfizer omicron-specific trial, at my three-month visit last week following my booster that was either the omicron vaccine or the original, I was unblinded, and offered another booster, which was definitely the omicron-specific vaccine. I had been in the control group, and had received the original vaccine. I'll be giving them some more blood tomorrow, one week after my omicron-specific booster. This is the first time they've wanted blood so soon after the shot. Previously, it has always been one-month after the shot. The staff mentioned that there are a bunch of sub-studies they're keeping track of.

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John Skylar, PhD's avatar

That is fascinating, thank you for sharing!

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Linda Post's avatar

Thanks for the lesson on statistics and the skew in the Lancet article! However, I have to say that I thought the point of the Lancet article was to produce data on how the efficacy of the vaccines waned over time. Given that fact I thought 50% was pretty good given the variable efficacy of the flu shot from year to year!

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John Skylar, PhD's avatar

I think that was definitely the point of the article--but it missed the mark largely because of the nature of the dataset. I agree with you that 50-60% is actually pretty good, but we need to recalibrate to a different baseline, which goes unmentioned in the Lancet article.

One thing that is important to me in the conversation about "waning" COVID-19 immunity is that we understand what waning actually means. In my thinking, waning is when a host-determined immune response weakens over time because of host-determined factors.

A situation where more people in the population are immune and so the apparent VE falls for numeric reasons? That's not waning, that's a transition from a naive population to a more disease-experienced one. So I wanted to call that out.

But there are things that in the last couple of years have been called waning that I would also call by another name. For example, a lot of ink was spilled about waning of vaccines vs the Delta variant, when it seems to me that what happened was the Delta variant had some meaningful antibody escape mutations. A few sets of data supported a narrative that the changes were virus-driven and not host-determined.

Likewise, with the Omicron variant, I don't think the vaccines have "waned" so much as the virus has escaped the immune response. There is a type of waning that we see with Omicron--booster doses generate elevated neutralizing antibodies that hit the Omicron variant, and then these fall because they are not the dominant antibodies generated--but that does not explain the effects seen entirely, or at least is obfuscates what's really going on. In reality, it's the dominant antibodies we ought to be asking about, and they are specific to an older variant of the virus...and would, I imagine, be completely sufficient to fully protect a person against that variant. So we see lots of headlines about "waning" when I think it more rightly should be called virus evolution and escape.

What to do about that phenomenon is a different question--and one I don't currently have the data to answer--but I do think it's important that we pick apart the usage of the word "waning" and assess what the actual cause is. It's far too easy to look at falling VE and conclude, wrongly, that the vaccines "don't work" because they are less effective at combating a virus that has evolved to escape human immune responses to its older cousins, when those older cousins are what the vaccines specifically were made to fight. The vaccines work fine--the virus has just found a way to evade them. Which tells us something about how we might get around that problem.

Likewise this statistical bias situation is informative because it tells us something about whether the vaccines are working better than natural infection, which to me is very interesting.

Anyway I've gone on quite a bit here, but the key thing I'm trying to convey is that people talk about "waning" a lot when, much of the time, there is a better explanation that actually tells us more about the pandemic than this blanket term might reveal.

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Carl Fink's avatar

"Last issue sparked some really interesting discussion about antivirals, and also about progress towards approval of a pediatric vaccine. I recommend going back and reading those discussions!" Except ... look down below. That article is not linked from this one, for whatever reason.

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John Skylar, PhD's avatar

I don't typically link the previous issue's comment thread from new issues.

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Carl Fink's avatar

No, the *article itself* isn't linked in the list of previous articles at the bottom. The last one shown is from 4/7.

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John Skylar, PhD's avatar

Oh, weird. That's generated by substack, so I don't know what goes into their algorithm's decision-making process. Maybe the 4-7 issue was more popular than the last one.

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Carl Fink's avatar

I got a notification of one of those nonsense-spewing comments, but by the time I clicked on the link in the email, you had already deleted it.

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