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Originally Posted by opendoor
PCR cycle counts aren't really a great proxy for viral load or replication levels. They pick up dead and neutralized virions, which is why you can test positive for months after recovery. Only culture tests which determine the level of live virus are useful for determining this, and they have repeatedly shown that immunologically naive people have significantly higher viral levels.
And of course, even if peak viral load was similar, the duration of infection (and replication) is shorter with prior immunity, so the total number of replications is lower.
It has to overcome it, but it doesn't make it more likely. Mutations are random, so the threshold for a new variant to spread is higher with immunity. So yes, there is evolutionary pressure to evade immunity, but because immune evasion generally requires a fairly significant number of mutations, the bar is higher.
And ultimately, partially overcoming immunity isn't necessarily a big deal, as long as there isn't a corresponding increase in severity. That's what we see with other coronaviruses.
It normally takes a week or so of someone being infectious before they end up with a severe infection, and for much of that period there is little distinction between mild and severe COVID. That and pre-symptomatic spread are things that make COVID so infectious.
You're misunderstanding what I said. You asked why other coronaviruses haven't randomly become deadly, and why COVID would be more likely to do that than the other circulating coronaviruses. I said, that's because they're far less severe. To become deadly like COVID is, they'd have to become vastly more severe as a result of a mutation, which is basically impossible for any coronavirus, barring a recombination with a more severe variant (which is exceedingly unlikely in humans).
But the rate of mutation is lower for the reasons I outlined (immunity reducing the genetic diversity and allowing the body to neutralize the virus faster).
They also may be inherently more stable too, but it's hard to know that so early into SARS-CoV-2's existence. Though it is speculated that the Russian Flu in 1889-1890 was actually the introduction of the OC43 coronavirus into the human population. But once it circulated enough, there were no longer immunologically naive people (other than infants) so the burden dropped significantly over the years.
Think about the bolded for a second. So vaccinated/previously infected people are infected for a shorter period of time, yet that doesn't lead to fewer replications? How does that make any sense?
Again, the proof is really in what we're seeing. If immunity encourages dangerous mutations, then why was the rate of new variants of concern per infection vastly higher in the first year of the pandemic compared to now? We should have seen 10-20 changes equivalent to Alpha, Delta, or Beta based on the number of post-Omicron infections. And why haven't we seen significant mutations in the other circulating coronaviruses over the decades?
The answer is, an immunologically naive population is like a blank canvas. The virus will mutate and basically any type of mutation has the chance to become dominant. So if it mutates to become more severe, well there's nothing to really stop that as long as it can spread effectively. But with immunity, if it randomly mutates to become more severe, chances are it will die out almost immediately (and before being detected) as it hits a wall of immunity.
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You're fundamentally misinterpreting the way viruses spread in the body. It's not a slow spread. Each one of the initial cells that gets infected will then make hundreds of thousands of copies and all the vulnerable cells are exposed within 1-4 days (depending on strain), at which point the a full blown immune response typically kicks in.
By this time, the body will have been at full viral load, and the vast majority of the cells that are going to be infected, are already infected. With Covid-19, between 1-10% of lung cells are considered vulnerable, and only a small percentage of those ever become infected. No one is sure why some cells get infected and other don't.
Clean up, also doesn't refer to how long replications go on for, but how long the active virus particles, that have already been produced, remain in the body. With a targeted immune response, the clean up of these existing virus particles happens quicker. However, even then it's pretty marginal.
It's not like the virus is slowly spreading through the body and you're dealing with new cells getting infected.
I also don't know what you're talking about in terms of proof of new variants. The new variants started to explode in number around the time that more people were getting infected. Once again, past the first 4-6 months there was no real advantage to infection against protection by vaccination. A dangerous variant is just as likely to arise in an unvaccinated/vaccinated person, but only a person with existing immunity is likely to create a variant that evades immunity.
I agree with your point about functional mutation, you're most likely looking at requiring several base mutations. Although, that's not entirely certain, as it could be just a single base mutation, that's unlucky that could result in non-binding of some immune cell. Single base mutations can, for example, change the 3-dimentional structure of a protein (or RNA/DNA strand). Also I don't get where you're getting the idea that it takes more mutations to have an immunity evading mutation than one that affects how deadly the virus is. You're literally just making that up. For example, a mutation that results in faster replication or binding to a different tissue in the body, could require
a somewhat fundamental change to the virus. There could also actually even be a single mutation that results in both a deadlier and more evasive virus.