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> the more it'll have to make those costly evolutionary choices and become less virulent Why would evolution select for less virulence in a virus like this? Gi

by wycy 5y ago

> the more it'll have to make those costly evolutionary choices and become less virulent Why would evolution select for less virulence in a virus like this? Given covid doesn't rely on symptoms to spread like the common cold seems to, it would seem like the evolutionary pressure would be the opposite. Rather than moderate symptoms, instead jack up viral loads in the host as quickly as possible to spread before the immune system gets involved. /not a biologist

XorNot 5y ago
There's physical limitations on what it can do, basically. Every mutation runs the risk of reducing its binding affinity to ACE receptors to get inside cells - or might impede cell entry functions. Given the amount of infection out there, whatever "easy" mutations might've been available to it clearly haven't been very useful in increasing its rate of spread - and haven't touched anything the vaccines target. So it's quite likely that whatever needs to happen to evade the vaccines is otherwise deleterious to its virulence.
lamontcg 5y ago
That is what it is doing right now. But it is doing that in response to evolutionary pressure because when a good fraction of the people are recovered or vaccinated then an R0 of 3.0 doesn't work as well when its chasing after those remaining susceptible people. There'll be an upper limit to how much it can increase its binding to ACE / viral load / R0 though. Once you hit that point infections should fall off a cliff. Then the virus will start to come under pressure to achieve immune escape. To really achieve immune escape the virus should have to make costly mutations. It shouldn't be able to pick the most optimized spike conformation, it'll have to pick a spike conformation that immune systems don't recognize. It can't be ruled out that the virus has so much "room" to mutate on the spike protein that high virulence total escape mutants could be formed, but probably not. There are estimated to be 20 epitopes on the spike that the immune system recognizes and to really escape it needs to mutate sufficient to change all of them. Some of them are likely to be expensive to the virus. And if we get booster shots like I said to box it in more, then it should run out of room and start to mutate more towards stealth and less towards virulence. And there's historical parallels to 1918. At first the H1N1 virus came back in waves that became more virulent. Then once more than half the world had been infected it started to come back as seasonal influenza and spread endemically in humans until 1957. Some of that is likely partial immunity from previously infected individuals, some of that is probably that the virus stated to favor evolving to escape detection and not for virulence and transmissibility.

by wycy 5y ago

XorNot 5y ago

There's physical limitations on what it can do, basically. Every mutation runs the risk of reducing its binding affinity to ACE receptors to get inside cells - or might impede cell entry functions. Given the amount of infection out there, whatever "easy" mutations might've been available to it clearly haven't been very useful in increasing its rate of spread - and haven't touched anything the vaccines target. So it's quite likely that whatever needs to happen to evade the vaccines is otherwise deleterious to its virulence.

lamontcg 5y ago

That is what it is doing right now. But it is doing that in response to evolutionary pressure because when a good fraction of the people are recovered or vaccinated then an R0 of 3.0 doesn't work as well when its chasing after those remaining susceptible people. There'll be an upper limit to how much it can increase its binding to ACE / viral load / R0 though. Once you hit that point infections should fall off a cliff. Then the virus will start to come under pressure to achieve immune escape. To really achieve immune escape the virus should have to make costly mutations. It shouldn't be able to pick the most optimized spike conformation, it'll have to pick a spike conformation that immune systems don't recognize. It can't be ruled out that the virus has so much "room" to mutate on the spike protein that high virulence total escape mutants could be formed, but probably not. There are estimated to be 20 epitopes on the spike that the immune system recognizes and to really escape it needs to mutate sufficient to change all of them. Some of them are likely to be expensive to the virus. And if we get booster shots like I said to box it in more, then it should run out of room and start to mutate more towards stealth and less towards virulence. And there's historical parallels to 1918. At first the H1N1 virus came back in waves that became more virulent. Then once more than half the world had been infected it started to come back as seasonal influenza and spread endemically in humans until 1957. Some of that is likely partial immunity from previously infected individuals, some of that is probably that the virus stated to favor evolving to escape detection and not for virulence and transmissibility.