By which mechanism does immunity favor new Covid variants?

post by anorangic · 2021-04-04T10:24:20.691Z · LW · GW · No comments

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    CellBioGuy
    cistran
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I'm not a biologist, but I'm trying to get something like a gears-level understanding of the situation we are in. There are phenomena that seem superficially clear to me, but if I'm honest, I do not really understand what's going on.

For example, take the new Covid variants from Great Britain, South Africa and India. It is often said that the danger for such mutations is higher if a population already has some immunity because it increases the selection pressure. First, I thought "that's obvious, it's just how evolution works". But, how exactly does this work?

Here is my current understanding:
* Viruses do not have a metabolism, which is why I suspect that there is no strong competition in the human body among different virus variants. (Please correct me if this is wrong -- I asked some friends doing biology but they also could not tell me whether this is true.)
* Immunity essentially disadvantages the "old" variant, but because of the first point, it does not give any advantage to the "new" variants.
* Although the share of the more contagious, new variants are higher with some existing immunity, in absolute numbers, the new variants are not more successful than without immunity.
* It even seems plausible (and for some variants, there's evidence) that immunity agains the old variant also gives partial immunity agains the new variants.
* I conclude that the presence of the new variants is mainly driven by the mere number of viruses, which is proportional to the number of mutations. When the number of viruses increases, the chance of a dangerous mutation also increases. However, immunity seems to be a good thing to mitigate mutations in every case.

Unfortunately, I must have made a mistake somewhere because experts say otherwise.
I'd be grateful for suggestions how this mechanism "immunity -> selection pressure -> more creepy variants" really works!

Answers

answer by CellBioGuy · 2021-04-06T03:58:34.201Z · LW(p) · GW(p)

Taking this off in a different direction.

The selection pressure driving these things into existence is HIGHLY convergent all around the world, with about four mutations appearing again and again and again.  This is adaptation to the human host, not really evolution for immune evasion, especially considering that only like 30% of most populations at most has been infected.

You would expect immune evasion selection to be wildly divergent rather than convergent.  What is mostly happening is an interaction between the fact that regions of spike protein that are on the surface of the spike and are involved in host interactions are evolving to do do well in a new host, and the fact that these functional regions of host interaction are under many selective pressures and more likely to be 'sticky' and places where functionally important antibodies tend to bind.  Slight immune evasion is a side effect, not what drove them into existence in the first place, for the most part.

comment by anorangic · 2021-04-14T09:55:27.765Z · LW(p) · GW(p)

So could I summarize this as follows? The MPG asserts in the linked article that the rapid evolution might arise from pre-existing immunity in a population because of some "increasing [...] selection pressure". On the other hand, you argue since that the new variants did not just change superficially to evade being recognized but seemed to have adapted to the human host, and this is not what one would expect if the main driving force would be immune evasion.

Thanks for you response -- if you have any thoughts to this proposal for a summary, I'd be very interested.

answer by cistran · 2021-04-06T06:58:02.530Z · LW(p) · GW(p)

First, there should be competition between different virus variants for the cells to infect. This paper

( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426218/) discusses competitive exclusion for shorter infection cascades.

Second, there are viruses that evolved to coexist with immune system and maintain stable populations inside human host without provoking super-exponential immune response. New variants of corona viruses that gain this ability will become permanent residents in people who are partially immune. Eventually these variants will constitute a majority of corona virus populations in human hosts.

comment by anorangic · 2021-04-14T13:36:47.487Z · LW(p) · GW(p)

Nice discovery! I will look into it.
In my naive understanding, I imagine that each strain only infects a small fraction of all cells, so that two strains should rarely infect the same cell. On the other hand, the abstract explicitly mentions competition between strains, suggesting that there must be connection to multiple infection of cells.

comment by tkpwaeub (gabriel-holmes) · 2021-04-15T01:30:31.651Z · LW(p) · GW(p)

This reminds me - have you read about some of the connections between covid outcomes and cytomegalovirus? It's pretty fascinating. 

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