COVID variants have mutated in the direction of faster spread and less immunity, as expected. They also seem to be mutating to higher disease severity, which was not expected. Why would that be, and should we expect this to continue?
My current theory is that the reason variants are more severe is because there’s evolutionary pressure on a common factor that affects both severity and secondary attack rate, and that factor is viral replication rate.
In the initial stage of an infection, the number of virus-copies inside someone grows exponentially. If the spike protein mutates to get slightly more reliable, then the doubling time of that growth shrinks. Result: Increased viral shedding, decreased minimum infectious dose, increased severity.
I hypothesize that we’re used to respiratory diseases evolving towards lower severity because, first, they’ve already maxed out this particular axis, and second, because they rely on people walking around in public while symptomatic, which they won’t do if the disease is too severe.
This retrodicts that data pretty well, but I’m still really unsure whether severity in the future is going to rise or fall. One one hand: there’s probably still room left to increase replication rate further, and the people-walking-around-if-mild transmission method isn’t going to come back. On the other hand, COVID might reach (or already be in) a local optimum with respect to spike-protein efficiency, in which case selection for immune-evasion will mean evolving away from the most-efficient version.
COVID variants have mutated in the direction of faster spread and less immunity, as expected. They also seem to be mutating to higher disease severity, which was not expected. Why would that be, and should we expect this to continue?
My current theory is that the reason variants are more severe is because there’s evolutionary pressure on a common factor that affects both severity and secondary attack rate, and that factor is viral replication rate.
In the initial stage of an infection, the number of virus-copies inside someone grows exponentially. If the spike protein mutates to get slightly more reliable, then the doubling time of that growth shrinks. Result: Increased viral shedding, decreased minimum infectious dose, increased severity.
I hypothesize that we’re used to respiratory diseases evolving towards lower severity because, first, they’ve already maxed out this particular axis, and second, because they rely on people walking around in public while symptomatic, which they won’t do if the disease is too severe.
This retrodicts that data pretty well, but I’m still really unsure whether severity in the future is going to rise or fall. One one hand: there’s probably still room left to increase replication rate further, and the people-walking-around-if-mild transmission method isn’t going to come back. On the other hand, COVID might reach (or already be in) a local optimum with respect to spike-protein efficiency, in which case selection for immune-evasion will mean evolving away from the most-efficient version.
(Crossposted with Facebook)
I highly recommend reading something about mainstream research on this topic:
https://pubmed.ncbi.nlm.nih.gov/19196383/