My (highly speculative!) hypothesis is that the emergence of these variant viruses arises in cases of chronic infection during which the immune system places great pressure on the virus to escape immunity and the virus does so by getting really good at getting into cells. 11⁄19
That’s plausible, but doesn’t explain why the chronic infections hadn’t done this earlier, and the English strain doesn’t escape immunity in this way (and we don’t know about the others) so I notice it doesn’t feel like it explains things.
That isn’t plausible to me. Not only does it not explain everything, I don’t think it explains anything. There are two traits, immune escape and infectiousness, which is pretty much the same as fitness. It makes sense that chronic infection causes immune escape, but we aren’t looking at immune escape. There might be tons of strains with immune escape out there, but we won’t notice until we achieve substantial herd immunity, at which point they will have increased fitness. If that happens, and we need to explain immune escape in future strains, then this is a possibility. But I see no reason to believe it about these strains. We are filtering by increased fitness, so we need to explain increased fitness. Immune escape is probably a side effect of increased fitness, because it’s a potential side effect of any change.
Fitness is fitness. There is no need for a weird environment to explain selection for fitness, because it’s the main story. In fact, this is exactly backwards. If there is any trade-off between reproduction between hosts and reproduction in hosts, then selection by chronic infection will favor the latter at the expense of the former and probably move away from optimal fitness. Whereas it appears, as Bedford claims, that these mutations are a free lunch. This is quite plausible for a young parasite that hasn’t finished adapting to its new host. But then what does a weird selection pressure explain? Every infection should be an opportunity to develop this. What matters is the number of roughly the number of virus-host-days. A virus trapped in one individual for 100 days is under roughly the same selection pressure as a virus passing through 20 individuals under the same time. I’ve seen a lot of people call that “fast evolution” because 20x as much selection happens in the host, but it’s not any faster in time.
Bedford seems to allude to this view, but he also uses similar points to make a different argument, which is that the UK variant appeared out of nowhere with a lot of mutations, without the intermediate forms being observed. Arising from a chronic infection would explain this. But we also know that all the mutations have arisen before, without seeming to do much on their own. So we know that it only took off when it reached the magic combination, which explains why we didn’t see the intermediate forms. I don’t think chronic infection adds much to this, although I could imagine a scenario in which the individual changes happen to be selected for in chronic infection at the slight expense of general fitness. So it needs the different landscape of a chronic infection to cross the valley and reach the final form. But this seems like excess detail to me.
All makes sense, but I would note that if a strain had escaped sufficiently to fully reinfect, that would be a huge advantage already, 20%+ of the population has already been infected including most of those taking them most risks.
Dynamically, that predicts that the advantage would rise over time, as a substantial proportion of the population got infected by the original strain. I think we’ve been monitoring the UK variant enough to see that this is not a large portion of its advantage.
Even statically, I think it’s difficult to make the numbers work out. The idea that the population has heterogeneous risk makes a lot of sense, but it doesn’t seem born out by the basic prediction that HIT is much lower than predicted by initial R. I suppose the control system might make it hard to observe how close we are getting to HIT, but I’m skeptical. And you need zero cross-immunity. But then wouldn’t the observed reinfections skyrocket and be obvious? Maybe if the reinfections are asymptomatic, but just as contagious. I guess that this very specific scenario predicts that the new variant has passed through the riskiest portion of the London population and no longer has an advantage there.
That isn’t plausible to me. Not only does it not explain everything, I don’t think it explains anything. There are two traits, immune escape and infectiousness, which is pretty much the same as fitness. It makes sense that chronic infection causes immune escape, but we aren’t looking at immune escape. There might be tons of strains with immune escape out there, but we won’t notice until we achieve substantial herd immunity, at which point they will have increased fitness. If that happens, and we need to explain immune escape in future strains, then this is a possibility. But I see no reason to believe it about these strains. We are filtering by increased fitness, so we need to explain increased fitness. Immune escape is probably a side effect of increased fitness, because it’s a potential side effect of any change.
Fitness is fitness. There is no need for a weird environment to explain selection for fitness, because it’s the main story. In fact, this is exactly backwards. If there is any trade-off between reproduction between hosts and reproduction in hosts, then selection by chronic infection will favor the latter at the expense of the former and probably move away from optimal fitness. Whereas it appears, as Bedford claims, that these mutations are a free lunch. This is quite plausible for a young parasite that hasn’t finished adapting to its new host. But then what does a weird selection pressure explain? Every infection should be an opportunity to develop this. What matters is the number of roughly the number of virus-host-days. A virus trapped in one individual for 100 days is under roughly the same selection pressure as a virus passing through 20 individuals under the same time. I’ve seen a lot of people call that “fast evolution” because 20x as much selection happens in the host, but it’s not any faster in time.
Bedford seems to allude to this view, but he also uses similar points to make a different argument, which is that the UK variant appeared out of nowhere with a lot of mutations, without the intermediate forms being observed. Arising from a chronic infection would explain this. But we also know that all the mutations have arisen before, without seeming to do much on their own. So we know that it only took off when it reached the magic combination, which explains why we didn’t see the intermediate forms. I don’t think chronic infection adds much to this, although I could imagine a scenario in which the individual changes happen to be selected for in chronic infection at the slight expense of general fitness. So it needs the different landscape of a chronic infection to cross the valley and reach the final form. But this seems like excess detail to me.
All makes sense, but I would note that if a strain had escaped sufficiently to fully reinfect, that would be a huge advantage already, 20%+ of the population has already been infected including most of those taking them most risks.
Dynamically, that predicts that the advantage would rise over time, as a substantial proportion of the population got infected by the original strain. I think we’ve been monitoring the UK variant enough to see that this is not a large portion of its advantage.
Even statically, I think it’s difficult to make the numbers work out. The idea that the population has heterogeneous risk makes a lot of sense, but it doesn’t seem born out by the basic prediction that HIT is much lower than predicted by initial R. I suppose the control system might make it hard to observe how close we are getting to HIT, but I’m skeptical. And you need zero cross-immunity. But then wouldn’t the observed reinfections skyrocket and be obvious? Maybe if the reinfections are asymptomatic, but just as contagious. I guess that this very specific scenario predicts that the new variant has passed through the riskiest portion of the London population and no longer has an advantage there.