5 ms·

> We know that B.1.1.529 is not a “Delta plus” variant. The figure below shows a really long line, with no previous Delta ancestors. So this likely means it mut

> We know that B.1.1.529 is not a “Delta plus” variant. The figure below shows a really long line, with no previous Delta ancestors. So this likely means it mutated over time in one, likely immunocompromised, individual (see my P.S. note at the end of the post). How does that work ? Virus mutate inside the host until either death or the immune system stops it ? Why is the absence of selective pressure producing a virus more efficient at spreading ?

biophysboy 5y ago
Genome replication mistakes occur rarely but naturally. The covid virus has a proofreading enzyme, but it isn't foolproof. Selective pressure is selective, not creative. With more complex organisms, its more, well, complex because they can do things like horizontal gene transfer. [EDIT]: But even here selective pressures just impose consequences, they don't cause HGT
contravariant 5y ago
This isn't really my area so this is conjecture and guesswork. If various immunocompromised people get infected then by a fluke their immune system could be just powerful enough to contain the infection but not eradicate it, this will remain the case until the virus becomes too powerful and the host dies. It's not the absence of selective pressure that is driving the mutation here, it's the mere fact that the virus might survive the selective pressure that does it. Also from some of the explanations I've read of Covid-19 the mere duplication of the virus isn't all that damaging, the harsh way the immune system eradicates infected cells is more damaging. So someone with a limited immune response might survive for a surprisingly long time.
- biophysboy 5y ago
  This is closer to my area, you're basically right. Viruses copy a lot in immunocompromised people for a long time. Lots of copying is all ya need to make variants.
  - ed_balls 5y ago
    Since immunocompromised people haven't "produced" super flu variant so far, is it safe to assuming we won't have it with Covid? I may spread faster, but won't be more deadly.
    - tsimionescu 5y ago
      Possibly, but spreading faster is much more deadly than being more deadly - at least for a disease that already starts at a high death rate like Covid does. This happens because living sick people help spread the disease, while dead people don't.
    - tsol 5y ago
      The general tendency is for viruses to become less deadly with increasing mutations. Highly deadly strains kill too quickly to spread well, whereas the common cold kills relatively few but hangs around long enough to keep moving from person to person. Viruses dont "care" to kill people, viruses only "want" to spread. That's what drives a viruses growth
      - ed_balls 5y ago
        That is not true for Covid. It's an upper respiratory virus which infects others before causing symptoms. It's possible to develop a variant that spreads, but kills everybody (highly unlikely in practice). There is no strong evolutionary pressure like in case of SARS-COV-1
etiam 5y ago
I'm not an expert in this, but having said that: The selective pressure would typically not be completely absent, but hampered enough that the game can stay on much longer than usual. Conditions like that could be imagined to set up continued high copy numbers of virus, alongside a fierce internal competition for infection. The clone will get opportunity to diversify much more due to the long infection, so there is more of a chance for novel alleles to arise and compete against their ancestral form. And a weakened immune system gives more leeway for incremental improvement of marginal advantages. Somewhat allegorically, a new slight advantage escaping antibodies is worth nothing in context if every extra virion who escapes falls to phagocytes and cytotoxic T-cells. But if the other components are weakened, the selection pressure is unmasked. (At least it seems to me that should be the case in theory, I'm not sure if the effect is strong enough to be very important in practice in this context). > We know that B.1.1.529 is not a “Delta plus” variant. The figure below shows a really long line, with no previous Delta ancestors. So this likely means it mutated over time in one, likely immunocompromised, individual (see my P.S. note at the end of the post). This really stood out to catch my attention and imagination too. With "immunocompromised" and Sub-Saharan Africa juxtaposed, it's hard not to think HIV. If (when, really) they co-infect, SARS-CoV-2 would be working in the context of HIV reverse transcriptase, and that could potentially mean going from RNA to DNA (possibly with incorporation into host DNA) and then back again by route of regular transcription. No big stretch if that would mess with copying fidelity and introduce lots of new opportunities to pick up new sequences and corresponding abilities.
ed_balls 5y ago
https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/ https://www.scientificamerican.com/article/covid-variants-ma...
jsnell 5y ago
There is selective pressure, and in fact more than for a normal person! It is coming from them being treated with some kind of antibody treatment (e.g. convalescent plasma) but not to a level that would actually cure them. I just wrote a comment on this a few hours ago in another thread: https://news.ycombinator.com/item?id=29354300 https://news.ycombinator.com/item?id=29354300
- biophysboy 5y ago
  I think his confusion is that there doesn't seem to be a novel force that causes the virus to change. The person is the same, so the virus's situation is the same. But like you say, you don't need a new constraint, you just need enough time.
tapoxi 5y ago
First detected in Botswana, where apparently 20% of the population is HIV+.

biophysboy 5y ago

Genome replication mistakes occur rarely but naturally. The covid virus has a proofreading enzyme, but it isn't foolproof. Selective pressure is selective, not creative. With more complex organisms, its more, well, complex because they can do things like horizontal gene transfer. [EDIT]: But even here selective pressures just impose consequences, they don't cause HGT

contravariant 5y ago

This isn't really my area so this is conjecture and guesswork. If various immunocompromised people get infected then by a fluke their immune system could be just powerful enough to contain the infection but not eradicate it, this will remain the case until the virus becomes too powerful and the host dies. It's not the absence of selective pressure that is driving the mutation here, it's the mere fact that the virus might survive the selective pressure that does it. Also from some of the explanations I've read of Covid-19 the mere duplication of the virus isn't all that damaging, the harsh way the immune system eradicates infected cells is more damaging. So someone with a limited immune response might survive for a surprisingly long time.

biophysboy 5y ago
This is closer to my area, you're basically right. Viruses copy a lot in immunocompromised people for a long time. Lots of copying is all ya need to make variants.
- ed_balls 5y ago
  Since immunocompromised people haven't "produced" super flu variant so far, is it safe to assuming we won't have it with Covid? I may spread faster, but won't be more deadly.
  - tsimionescu 5y ago
    Possibly, but spreading faster is much more deadly than being more deadly - at least for a disease that already starts at a high death rate like Covid does. This happens because living sick people help spread the disease, while dead people don't.
  - tsol 5y ago
    The general tendency is for viruses to become less deadly with increasing mutations. Highly deadly strains kill too quickly to spread well, whereas the common cold kills relatively few but hangs around long enough to keep moving from person to person. Viruses dont "care" to kill people, viruses only "want" to spread. That's what drives a viruses growth
    - ed_balls 5y ago
      That is not true for Covid. It's an upper respiratory virus which infects others before causing symptoms. It's possible to develop a variant that spreads, but kills everybody (highly unlikely in practice). There is no strong evolutionary pressure like in case of SARS-COV-1

etiam 5y ago

I'm not an expert in this, but having said that: The selective pressure would typically not be completely absent, but hampered enough that the game can stay on much longer than usual. Conditions like that could be imagined to set up continued high copy numbers of virus, alongside a fierce internal competition for infection. The clone will get opportunity to diversify much more due to the long infection, so there is more of a chance for novel alleles to arise and compete against their ancestral form. And a weakened immune system gives more leeway for incremental improvement of marginal advantages. Somewhat allegorically, a new slight advantage escaping antibodies is worth nothing in context if every extra virion who escapes falls to phagocytes and cytotoxic T-cells. But if the other components are weakened, the selection pressure is unmasked. (At least it seems to me that should be the case in theory, I'm not sure if the effect is strong enough to be very important in practice in this context). > We know that B.1.1.529 is not a “Delta plus” variant. The figure below shows a really long line, with no previous Delta ancestors. So this likely means it mutated over time in one, likely immunocompromised, individual (see my P.S. note at the end of the post). This really stood out to catch my attention and imagination too. With "immunocompromised" and Sub-Saharan Africa juxtaposed, it's hard not to think HIV. If (when, really) they co-infect, SARS-CoV-2 would be working in the context of HIV reverse transcriptase, and that could potentially mean going from RNA to DNA (possibly with incorporation into host DNA) and then back again by route of regular transcription. No big stretch if that would mess with copying fidelity and introduce lots of new opportunities to pick up new sequences and corresponding abilities.

ed_balls 5y ago

https://www.scientificamerican.com/article/covid-variants-may-arise-in-people-with-compromised-immune-systems/ https://www.scientificamerican.com/article/covid-variants-ma...

jsnell 5y ago

There is selective pressure, and in fact more than for a normal person! It is coming from them being treated with some kind of antibody treatment (e.g. convalescent plasma) but not to a level that would actually cure them. I just wrote a comment on this a few hours ago in another thread: https://news.ycombinator.com/item?id=29354300 https://news.ycombinator.com/item?id=29354300

biophysboy 5y ago
I think his confusion is that there doesn't seem to be a novel force that causes the virus to change. The person is the same, so the virus's situation is the same. But like you say, you don't need a new constraint, you just need enough time.

tapoxi 5y ago

First detected in Botswana, where apparently 20% of the population is HIV+.