Thread by @ToddZywicki

I've referenced this paper on breakthrough infections in SF multiple times since it appeared. It is now published with lots of additional detail. This is the smoking gun that shows on a micro level the vax select for more vax-evasive variants. nature.com/articles/s4156…

To summarize the simple logic--natural selection consists of 3 elements: (1) variation, (2) selection, (3) replication.

Anybody who gets infected can create variation, regardless of whether vaxxed, partially vaxxed, unvaxxed, or boosted. Most variations don't replicate widely because at any given time the current version of the virus is best adapted to its environment so adaptations are less fit.

What matters is selection. For the first year of the pandemic there was one mutation at first and then relative "evolutionary stasis" for 11 months. As predicted.

Mass vax changed the selection pressure on the virus. What this paper shows is critical--whereas unvaxxed people were contracting a grab-bag of different variants, vaxxed people were disproportionately contracting and transmitting more vax-resistant variants: 78% v 48%. Duh.

Then add in the high density and high rates of transmission in SF and you get a very rapid spread of vax-resistant variants--which is why Delta took over so rapidly wherever mass vax was implemented. Vax were spreading it in preference to less-evasive variants.

If you try to explain this to the dumb True Believers they'll mutter something about the unvaxxed being "variant factories" so it must be their fault. They are missing the point--variation is irrelevant. Selection and replication are what matter!

Once you exert selection pressure on a mutable, evolving organism the end result is inevitable if there is enough replication--it inevitably will evolve toward vaccine escape. It is only a matter of how long it takes. But the end result is inevitable.

Given the high level of replication in the world (this is what is meant by "vaccinating into a pandemic") the rate of replication is high. So it didn't take long!

This is why it is so idiotically misguided to try to compare these vaxxes to earlier vaxxes. Not just because they are leaky. But because this virus evolves rapidly (unlike, say, measles). But also our other vaxxes were delivered against a background of high natural/herd immunity

By the time we administered the measles vax, for example, almost everyone living had natural immunity. So replication rates were low. So it was just a matter of vaxxing kids as they came into the population.

That's why this SF study is so important. Delta emerged and became dominant so rapidly, this is the only study I've seen that actually captures the precise window in time to see the mechanism in action.

And, of course, that is exactly what Omicron is doing right now. It is even more vax-evasive than Delta (slightly more NI-evasive too but much less so)--iso much so it feeds on the vaxxed (negative VE).

Final note--it remains unclear where O originated. Many smart people think it might have come from an animal host. But that proves the point of not getting fixated on the happenstance of where variation comes from. What matters is SELECTION and REPLICATION, not variation!