Forensic Analysis of Novel SARS2r-CoV Identified in Game Animal Datasets in China Shows Evolutionary Relationship to Pangolin GX CoV Clade and Apparent Genetic Experimentation
"Does it mean that single individuals really do typically infect dozens, if not hundreds, of others?"
To be fair, it is likely true that other means of spreading were indeed not evaluated, but there is actually lots of evidence this is the case. In general, but also for COVID-19. In the early days when people did contact tracing, and in some countries, they kept up with that pretty long, it was frequently seen that many people infect nobody outside their household (as in the infection chain dies out), or infected multiple people. So infecting hundreds is perhaps a bit much, but there is a lot of evidence that R-values have two peaks - one at 0 (households hence excluded) and one more significantly above the average R-value. The latter hence expressing the relevant R-distribution.
We've talked about this in the context of mutations, where I used the musical chair game example, where at each turn most chairs are eliminated, but afterwards all chairs are returned and survivors can all clone to take the empty seats. Such a model explains aggressive variant-die out despite hosts not being depleted, as well as I believe the seemingly absence of mutations.
I'm open to other means of spreading. But other than the release/appearance of the Omicron twins, I've seen no variants yet that cannot be explained by this model. But you often surprise me, so I'll hold my peace.
I'm fine with the musical chairs model of clade die-out, i.e. genetic sweeps. The first question then would be why do none of the 2020 VOCs themselves produce future MC winners? The winners we got, i.e. the 2020 VOCs and then the Omicrons, all come from pre-VOC "stock," either B.1 / B.1.1 or local descendent clades that were still out-of-date by late 2020. You never see a "Beta-descendent MC winner."
With flu, these kind of HA sweeps are always iterative, they don't reset from expired HAs.
The second question is why has sweeping stopped in the Omicron era? Now we just have a normal polyclonal population shifting around and convergent-evolving under natural immunity pressure, which suggests (along with generic human coronavirus genetic diversity) that flu sweeps aren't necessarily an appropriate model for coronaviruses anyway.
Both are very good questions for which I do not have a very good answer.
My tentative answer would be, because all the cliffs have been jumped.
All VOC's got created in just a few months. E.g. September 2020 (Alpha) - October 2020 (Beta and Delta). After that we had no new variants until the Omicron release/appearance. No other VOC' got hold despite the WHO passing out Greek letters like candy. So in a way we had only a burst of VOC's despite it took them a few months to settle the score.
So my answer is kind of, we did not have much VOC's to begin with after an initial set all based on B.1/B.1.1 So you could argue that after some experiments with different Tony Honk move sets, one set (Delta) just became the best and hence dominated. Hence the world became boring as we all did Delta. (Until Omicron came and cheated by moving to the upper respiratory trac changing the game itself.)
For Omicron similar, there are no cliffs anymore.
But I admit this is far from a definitive explanation. It is just that I don't think there is an issue perse. For a virus that jumps to humans in the second half of 2019, I'd don't think it is inherently unreasonable to expect convergence and stabilisation after a while.
(Flu I think is different, it not having a true/large receptor binding protein. So it has much more flexibility and is indeed not necessarily an appropriate model for coronaviruses.)
That's a great post and I am struggling with the same questions. How many of the "variants" were lab designed vs naturally evolved. The initial Omicrons were possibly designed around Jul-Aug of 2021.
The problem with all the 2020 VOCs is a lack of background signature - there are few synonymous mutations, few C>U mutations, and no mutations belonging to lineages that were still prevailing after spring 2020. So they somehow come from spring, mutate a lot without any detection, but none of these mutations are of the normal type that defines the lineages we do track from day to day. It would be a very strong case that they were lab made except the South America VOCs do have a few markers of local late spring lineages.
... or these mutations are just not viable, unless X of them happen together. It is kind of having to jump a far cliff. It doesn't matter if you got 10% or 99% of the way, you need 100% to survive. So in the genetic genome you'd find lots of large gaps, as in between variants are all inherently never seen.
Of course, that still leaves open if there are special circumstances that stimulate jumping the cliff. Is it all just random and the sheer unique never seen in our planet's lifetime volume of infections of humans caused this? As in the small chance is simply overcome by brute numeric force?
Or does it only happen in certain (e.g. immune compromised) hosts? And hence it is expected to see these, if one waits long enough?
Based on the sequence (https://www.ncbi.nlm.nih.gov/nuccore/MT007544.1) that one would be downstream of Wuhan, as opposed to of a B.1 clade, which isn't surprising since B.1 comes from Italy. Most of the outbreaks in the Austria paper are of B.1 / B.1.1 early mutants, just the tiny one was from a Wuhan-based sequence (hence why it is closer to the pin for Wuhan-Hu-1).
I still owe you a reply - your comment took some digesting and then I got busy, sorry for not responding and thank you for responding to me.
Still off topic, I have discovered a disturbing trend wherein I have dozens of posts now where I was the last person to comment after you. I sincerely apologize for pointing my red bum in your face. I don't know why this keeps happening but it happened again today!
Are these Unglossed posts? I haven't noticed the trend, so it would seem to be other substacks - though I scarcely go out to other substack comment threads any more.
Ah, I was confused by "comment" in your description. The like scroll isn't chronological, it just ranks all likes by some interaction algorithm, as well as always shows you on the left. It's one of substack's "let's always do what twitter / facebook does" features.
My apologies, it's late here and I'm an idiot. Sorry for confusing you. 🙂
Hmmm, I didn't know that, I would have thought it would be sequential. Well that would explain it then. Thank you for solving one of life's mysteries, I like it when that happens.
Still, I apologize for pointing my bum in your face. I have to say it makes me feel bad quite honestly. 😂
Forensic Analysis of Novel SARS2r-CoV Identified in Game Animal Datasets in China Shows Evolutionary Relationship to Pangolin GX CoV Clade and Apparent Genetic Experimentation
https://www.mdpi.com/2673-8007/2/4/68
"Does it mean that single individuals really do typically infect dozens, if not hundreds, of others?"
To be fair, it is likely true that other means of spreading were indeed not evaluated, but there is actually lots of evidence this is the case. In general, but also for COVID-19. In the early days when people did contact tracing, and in some countries, they kept up with that pretty long, it was frequently seen that many people infect nobody outside their household (as in the infection chain dies out), or infected multiple people. So infecting hundreds is perhaps a bit much, but there is a lot of evidence that R-values have two peaks - one at 0 (households hence excluded) and one more significantly above the average R-value. The latter hence expressing the relevant R-distribution.
We've talked about this in the context of mutations, where I used the musical chair game example, where at each turn most chairs are eliminated, but afterwards all chairs are returned and survivors can all clone to take the empty seats. Such a model explains aggressive variant-die out despite hosts not being depleted, as well as I believe the seemingly absence of mutations.
I'm open to other means of spreading. But other than the release/appearance of the Omicron twins, I've seen no variants yet that cannot be explained by this model. But you often surprise me, so I'll hold my peace.
I'm fine with the musical chairs model of clade die-out, i.e. genetic sweeps. The first question then would be why do none of the 2020 VOCs themselves produce future MC winners? The winners we got, i.e. the 2020 VOCs and then the Omicrons, all come from pre-VOC "stock," either B.1 / B.1.1 or local descendent clades that were still out-of-date by late 2020. You never see a "Beta-descendent MC winner."
With flu, these kind of HA sweeps are always iterative, they don't reset from expired HAs.
The second question is why has sweeping stopped in the Omicron era? Now we just have a normal polyclonal population shifting around and convergent-evolving under natural immunity pressure, which suggests (along with generic human coronavirus genetic diversity) that flu sweeps aren't necessarily an appropriate model for coronaviruses anyway.
Both are very good questions for which I do not have a very good answer.
My tentative answer would be, because all the cliffs have been jumped.
All VOC's got created in just a few months. E.g. September 2020 (Alpha) - October 2020 (Beta and Delta). After that we had no new variants until the Omicron release/appearance. No other VOC' got hold despite the WHO passing out Greek letters like candy. So in a way we had only a burst of VOC's despite it took them a few months to settle the score.
So my answer is kind of, we did not have much VOC's to begin with after an initial set all based on B.1/B.1.1 So you could argue that after some experiments with different Tony Honk move sets, one set (Delta) just became the best and hence dominated. Hence the world became boring as we all did Delta. (Until Omicron came and cheated by moving to the upper respiratory trac changing the game itself.)
For Omicron similar, there are no cliffs anymore.
But I admit this is far from a definitive explanation. It is just that I don't think there is an issue perse. For a virus that jumps to humans in the second half of 2019, I'd don't think it is inherently unreasonable to expect convergence and stabilisation after a while.
(Flu I think is different, it not having a true/large receptor binding protein. So it has much more flexibility and is indeed not necessarily an appropriate model for coronaviruses.)
That's a great post and I am struggling with the same questions. How many of the "variants" were lab designed vs naturally evolved. The initial Omicrons were possibly designed around Jul-Aug of 2021.
The problem with all the 2020 VOCs is a lack of background signature - there are few synonymous mutations, few C>U mutations, and no mutations belonging to lineages that were still prevailing after spring 2020. So they somehow come from spring, mutate a lot without any detection, but none of these mutations are of the normal type that defines the lineages we do track from day to day. It would be a very strong case that they were lab made except the South America VOCs do have a few markers of local late spring lineages.
... or these mutations are just not viable, unless X of them happen together. It is kind of having to jump a far cliff. It doesn't matter if you got 10% or 99% of the way, you need 100% to survive. So in the genetic genome you'd find lots of large gaps, as in between variants are all inherently never seen.
Of course, that still leaves open if there are special circumstances that stimulate jumping the cliff. Is it all just random and the sheer unique never seen in our planet's lifetime volume of infections of humans caused this? As in the small chance is simply overcome by brute numeric force?
Or does it only happen in certain (e.g. immune compromised) hosts? And hence it is expected to see these, if one waits long enough?
yep
This is very jnteresting Brian. I look forward to seeing your results.
Yellow soup for you! https://moderndiscontent.substack.com/p/fecal-microbial-transplants-and-gut
But in all seriousness, hope you get better asap.
All right, I'm really glad you're writing this series. I try not to miss a live stream with JJ Couey.
I hope you feel fully healthy again in no time. ❤️ Food poisoning can be awful!
Thanks!
First cultured Wuhan Covid19 outside of China was exported from Australia all over the world.
Compare sequences with Austria?
https://geoffpain.substack.com/p/first-detected-covid19-case-arrived
Based on the sequence (https://www.ncbi.nlm.nih.gov/nuccore/MT007544.1) that one would be downstream of Wuhan, as opposed to of a B.1 clade, which isn't surprising since B.1 comes from Italy. Most of the outbreaks in the Austria paper are of B.1 / B.1.1 early mutants, just the tiny one was from a Wuhan-based sequence (hence why it is closer to the pin for Wuhan-Hu-1).
Hi Brian, hope you feel better soon.
I still owe you a reply - your comment took some digesting and then I got busy, sorry for not responding and thank you for responding to me.
Still off topic, I have discovered a disturbing trend wherein I have dozens of posts now where I was the last person to comment after you. I sincerely apologize for pointing my red bum in your face. I don't know why this keeps happening but it happened again today!
https://i.imgur.com/zTbm71h.png
Thank you!
Are these Unglossed posts? I haven't noticed the trend, so it would seem to be other substacks - though I scarcely go out to other substack comment threads any more.
Hi Brian, no, I think you have more integrity than to like your own posts! Mostly Sage but a couple of others. It's really weird.
This was another:
https://imgur.com/a/sWujWqA
And it isn't the comment threads, just posts you liked. You obviously have great taste (as would I, it would appear!).
Ah, I was confused by "comment" in your description. The like scroll isn't chronological, it just ranks all likes by some interaction algorithm, as well as always shows you on the left. It's one of substack's "let's always do what twitter / facebook does" features.
My apologies, it's late here and I'm an idiot. Sorry for confusing you. 🙂
Hmmm, I didn't know that, I would have thought it would be sequential. Well that would explain it then. Thank you for solving one of life's mysteries, I like it when that happens.
Still, I apologize for pointing my bum in your face. I have to say it makes me feel bad quite honestly. 😂