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Slack / Private Message Drop, p.399 [SLACK_000613] · slack_pm:msg:04116

Date: 2021-01-14 15:20
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Andrew Rambaut
speaker: Edward C. Holmes

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Given the low frequency of chronic infections compared to the huge number with 'normal' durations of infection, doesn't the fact that we are seeing the same sort of constellation of mutations evolve and spread 3 times independently suggest that they have a major advantage at the population level?

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2021-01-14 14:27 Andrew Rambaut open

There is no evidence that there is increased transmissibility in either the Brazilian or South African strain.
2021-01-14 14:28 Andrew Rambaut open

It is clearly fit in the populations it is spreading in.
2021-01-14 14:38 Andrew Rambaut open

The convergence is possibly for cellular infectivity and immune evasion - all things that will be selected for in achronic infection without sterilising immunity. Strong competition between viruses for cells. However, my assumption has always been that this can only be likely to degrade transmissibility (given it was already transmissible at the beginning). But perhaps there is just a fortunate (for the virus) alignment of a within-host fitness peak and a between host one. And the latter involves too many intermediate steps with negative epistatic effects to reach in a stepwisefashion.
2021-01-14 14:39 Andrew Rambaut open

Within host (and with the additional benefit of recombination) these combinations are readily obtainable.
2021-01-14 15:20 Edward C. Holmes

Given the low frequency of chronic infections compared to the huge number with 'normal' durations of infection, doesn't the fact that we are seeing the same sort of constellation of mutations evolve and spread 3 times independently suggest that they have a major advantage at the population level?
2021-01-14 15:46 Andrew Rambaut open

Yes - they do. But I think they can't get there by progressive steps in sequential infections - there are troughs (wesee all of these mutations appear individually many times).
2021-01-14 15:47 Andrew Rambaut open

So the chronic infections offer an opportunity for these to arise in combination. Chronic infections are rare as aproportion of infections but there are shed loads of infections now.
2021-01-14 15:47 Edward C. Holmes open

Indeed. Not saying the theory is wrong, just that there are some loose ends. I can only imagine how Alina and ganghave reacted to this: [shared file(s): s41591-020-01205-5.pdf]
2021-01-14 15:54 Andrew Rambaut open

Nice piece. Angie is a true hero. I can't imagine what she must put up with (you probably can more than me, Eddie, but women get it so much worse).

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