[FRIAM] whackadoodles go mainstream!

Tue Apr 21 12:34:35 EDT 2020

Two naive questions.

1) Diseases mutate/evolve immunity or resistance to antibiotics, or so I believe i have been told. And I think this discussion notes that Covid evolves in response to pressures originating in the host. And I have read articles talking about genetic difference among hosts as partially responsible for the variance in severity of the disease. Is there a way to build some kind of "co-evolutionary" model — virus adapting to host / host adapting to virus — that would predict a stable minima? or is this whatis meant by "herd immunity?"

2) Supposedly (two articles, one in JAMA), 80% of COVID transmissions occur in homes, including nursing homes, and 34% occur in public transit, and near zero transmissions outside. (I know the numbers do not equal 100, but I think that is an artifact of being summarized.) Again supposedly, the only outbreaks from all the panned spring break activity were attributed to the public transport (airplanes) transmission, not to beach/party activity. Would it not be possible determine some kind of "person-density metric" — humans per cubic volume — that could be used as a basis for reopening stores, restaurants, etc. etc.

davew

On Tue, Apr 21, 2020, at 9:59 AM, Marcus Daniels wrote:
> Glen writes:
> 
> < I can see that the diversity seems to peak as the infections ramp up in the US and EU. And there's only a handful of spots where the diversity shoots up, only to level off later. >
> 
> Well, the color-coded phylogeny is looking at a tiny sampling of the infected world. I wouldn't draw any conclusion from that other than that viral drift is possible. It hasn't even been tabulated systematically against any phenotype besides where the sample was collected. Looking at the GenBank data, there are even variants within the same patient. 
> 
> Hopefully there will be engagement on compilation of anonymized clinical data outside of academia (esp. from hospitals and the major diagnostic labs). Then we can stop talking about what we "expect" and look at what actually happens! 
> 
> This morning I was told of this: https://covid19researchdatabase.org/
> 
> Marcus
> 
> 
> *From:* Friam <friam-bounces at redfish.com> on behalf of uǝlƃ ☣ <gepropella at gmail.com>
> *Sent:* Tuesday, April 21, 2020 9:36 AM
> *To:* FriAM <friam at redfish.com>
> *Subject:* Re: [FRIAM] whackadoodles go mainstream! 
> 
> Well, from the animation Marcus posted, even I can see that the diversity seems to peak as the infections ramp up in the US and EU. And there's only a handful of spots where the diversity shoots up, only to level off later.
> 
>  The Gorman article was very helpful. I suppose to really grok the inter-species vs. intra-species patterns enough to build an expectation, you'd have to work at a bat lab. By selecting h3n2 in the left panel, it seems the flu maintains a higher diversity across the board. So my 1st attempt at an expectation would be that a) jumping species, b) jumping species from a tolerant host like a bat, and c) the novelty of the strain should lead to a kind of pressure to get a better foothold in the hosts. Then as the host and parasite relax into one another, any obvious pressure would fade and it would look more random.
> 
>  Regardless of the design question, it seems like a virus that is *likely* to jump species in the first place would see less pressure to fit in immediately and would more quickly begin looking random.
> 
>  Anyway, thanks for your tolerance.
> 
>  On 4/20/20 5:15 PM, David Eric Smith wrote:
>  > Not my area of expertise, though for about the past year I have spent some time learning about proteins, so I am not as completely lost as I would have been before that.
>  > 
>  > The number of mechanisms that jointly get termed “evolution” in a complicated, mosaic, multi-host virus like this makes inference a many-dimensional problem.
>  > 
>  > Putting aside Marcus’s information on HLA variability, because I have not yet made the time to read it (though I hope to), just looking at the viral spike protein genes in the Nature letter to the editor, there seem to be at least two qualitatively different things going on. The six mutated positions in the receptor binding domain are interpreted by the letter’s authors as plausible convergent mutations. Since a lot of protein evolution seems to get locked in by structural or self-assembly constraints at many places, the number of labile positions on shorter timescales is some smaller number than the 20^211 that Marcus notes as an upper bound for brute force search (but again that is in the context of leukocytes, whereas these six mutations involve binding affinity to ACE2). But when we see two solutions that seem to be in completely different basins of attraction in humans, as SARS-CoV and SARS-CoV-2 appear to be, there looks to be a big valley of non-viability between
>  > them, with very low probability to have all mutations occur conjointly to cross it. I think people believe that between bats, cats et al., and now I guess pangolins (and I think I saw something about snakes from one letter that went around from an early researcher), there is an enormous reservoir of different strains, with a quite large diversity of ACE-type host proteins. So we would be looking for island-hopping routes that make the SARS-COV and SARS-CoV-2 solutions mutually intelligible. So the analysis of protein change mechanisms gets put into a larger context of ecological analysis of species contacts, which is probably as badly under-sampled as the viral diversity is.
>  > 
>  > The foregoing is independent of this “furin cleavage site”, and some special proline in a turn that facilitates attachment of surface amino-sugar chains. This article suggests that such features are under selection from either or both of infectivity based on how the proteins are translated, and immunosurveillance. Both of those will involve translational and immune proteins that vary significantly from one host to another. (I assume this is where HLA variability becomes central to this story.). There was an article in NYT a week or two ago by James Gorman on why bats seem to be a reservoir for “so many viruses”
>  >  https://www.nytimes.com/2020/01/28/science/bats-coronavirus-Wuhan.html
>  > (I don’t actually know whether they carry uncommonly more, per bat species, than other groups do per-species, since we often don’t know about things until they interest us enough to do a thorough survey, but if Gorman is writing with knowledge, that claim might be okay.). Certainly, there are an awfully large number of bats species, considering that they are just one little branch of insectivores. If there is something different about bat immune systems, which pairs in an important way with the genome evolutionary position of coronaviruses, that would seem to be the first place to look for immune selection, as context for later asking about what is different in people. The interesting thing is that these cleavage sites have not been found in other beta-lineage coronaviruses. (He doesn’t say where they have been found, though that shouldn’t be a hard dig to get to.). The suggestion is that the CoV-2 strain is a mosaic that is mostly beta-coronavirus with something else.
>  > The question is then, what else looks closest, where do the two occur together; what are the mechanisms for combining them. Now we are in an epidemiology/ecology question. 
>  > 
>  > Inferring a chain of origin with all these factors in play looks challenging to me. 
>  > 
>  > Eric
>  > 
>  > 
>  >> On Apr 21, 2020, at 8:35 AM, uǝlƃ ☣ <gepropella at gmail.com <mailto:gepropella at gmail.com>> wrote:
>  >>
>  >> What *would* you people who can read all this stuff *expect* to happen?
> 
> 
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