[opendoor]

Originally Posted by blankall

I agree with your first paragraph.

The main issue is selective pressure. So within a given genome the odds of having a mutation that incurs any kind of benefit are extremely low. Only when there is a selective pressure does that random mutation get propagated.

So for example, a person with no immunity and a person with immunity both have a mutation that occurs 1/1,000,000 replications (realistically meaninfull mutation probably occurs 1/trillions or more). Assuming it's not harmful (which the vast majority of mutations are) the person without immunity would expect to have only 1/1,000,000 viral particles would have the mutation, and if you're exposed to that person, the odds of you coming into contact with that mutation would be low. Meanwhile, the person with immunity and a mutation that carries evasion of that immunity would quickly have that new virus take over, and any further transmissions would be entirely that new evasive virus.

This is why the virus spreads in waves of strains the way it does. There is selective pressure to do so, amongst a population that already has significant immunity. This is especially true with our system of vaccines that no longer protect from actual infection.

But you need to be careful with how you put it. Yes, vaccines or prior immunity generate selective pressure on mutations that evade immunity, simply because anything that doesn't evade immunity is dead in the water. However, because mutations are random, prior immunity reduces the number of problematic mutations that are viable.

With little to no existing immunity, a virus just needs to mutate to become more severe without impacting its ability to spread and then you have a very real risk of a more severe variant taking over. That's what happened with prior variants. Once you have widespread immunity though, the virus needs to mutate to become more severe AND mutate in ways that it can evade immunity. That's a significantly higher threshold to clear, as immune evasion requires a fairly significant number of mutations generated through an iterative process of cumulative errors.

And this isn't just a theoretical thing; studies have found an inverse correlation between vaccination rates and the mutation frequency in SARS-CoV-2. As well as a significantly reduced mutation frequency in people with prior immunity, as immunologically naive people who get infected exhibit more mutational variance than vaccinated/previously infected people.

So yes, immunity will favor selection of immune evasive variants; that's obvious and it would be the case even vaccines were 100% effective. But the threat of more severe variants popping up is reduced with a higher level of immunity.

I don't know where you are getting this "more muted" mutation thing from? Are you talking about death rate and severity of symptoms? That has more to do with people having cross-over immunity and natural selective evolutionary pressures for viruses not to kill their hosts.

I mean less diversity. Alpha, Beta, Delta, and Gamma all existed by September of 2020, after there were ~100 million cumulative infections. Since Omicron took over, we've probably had 10-20x that many infections (including a vast number in people with some form of prior immunity), yet the currently circulating variants are still less distinct than the variants that popped up in the first 6-8 months of widespread infections.