New Covid Variants

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bob sterman
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Re: New Covid Variants

Post by bob sterman » Tue Jul 06, 2021 10:41 am

Bird on a Fire wrote:
Tue Jul 06, 2021 10:34 am
Not sure if that's a deliberate reference to the Red Queen hypothesis, but it's certainly apposite https://en.m.wikipedia.org/wiki/Red_Queen_hypothesis
Indeed. And our secret weapon is - sex - but as long-lived mammals we not really doing it fast enough!

Running with the Red Queen: Reflections on 'Sex versus Non-Sex versus Parasite'
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Re: New Covid Variants

Post by Bird on a Fire » Tue Jul 06, 2021 10:46 am

Man, I've really got to get my reproduction number up! ;)
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Re: New Covid Variants

Post by raven » Tue Jul 06, 2021 1:45 pm

hakwright wrote:
Mon Jul 05, 2021 12:26 pm
Delta is taking over in many EU countries, as we knew would happen. The fact it is happening in the middle of summer, with lots of fresh air and mostly outdoor interactions, just shows how easily it can be transmitted compared to Alpha.
That one of Bojo's reasons for complete unlocking on the 19th, wasn't it. That we need to get the spike out of the way now, in late summer, so we can be done with it by winter so we don't hit flu season/NHS peak demand.

Vaccinated population vs Delta is like unvaccinated vs wild strain
Certainly seems like it from the UK data. We've got 9 day doubling atm.

(I'm assuming vaccines that reduce transmission would increase doubling times. But do Pfizer et al do that, or do they just reduce severity? In fact, thinking about it, if they increase the fraction of cases that are asymptomatic that alone might increase transimission just because people won't know to isolate.... )

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Re: New Covid Variants

Post by Herainestold » Tue Jul 06, 2021 2:26 pm

raven wrote:
Tue Jul 06, 2021 1:45 pm
hakwright wrote:
Mon Jul 05, 2021 12:26 pm
Delta is taking over in many EU countries, as we knew would happen. The fact it is happening in the middle of summer, with lots of fresh air and mostly outdoor interactions, just shows how easily it can be transmitted compared to Alpha.
That one of Bojo's reasons for complete unlocking on the 19th, wasn't it. That we need to get the spike out of the way now, in late summer, so we can be done with it by winter so we don't hit flu season/NHS peak demand.

Vaccinated population vs Delta is like unvaccinated vs wild strain
Certainly seems like it from the UK data. We've got 9 day doubling atm.

(I'm assuming vaccines that reduce transmission would increase doubling times. But do Pfizer et al do that, or do they just reduce severity? In fact, thinking about it, if they increase the fraction of cases that are asymptomatic that alone might increase transimission just because people won't know to isolate.... )
I think thats exactly right. Vaccines are increasing transmission whilst reducing deaths. I can't quite imagine where this will take us, but it is not going to be a good place.
Delta changes everything.

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Re: New Covid Variants

Post by lpm » Tue Jul 06, 2021 3:07 pm

With an endemic global disease every likely variant will occur. There have been 180 million official cases, the true number is unknowable. The whole world is a variant factory.

There's been tens of thousands of strains, with a handful being highly successful - for example B.1.617.2 (Delta) being fitter for some reason than B.1.617.1 and B.1.617.3, both strains that were good but not good enough to win a Greek letter.

Evolutionary fitness isn't infinite. Most changes to the RNA are irrelevant. Surely it can't be that all viruses run through potential configurations and pick out the best each time - original defeated by Alpha, Alpha defeated by Delta, eventually Delta defeated by Zeta and Zeta defeated by Lambda until the end of time...? Otherwise viruses would all trend to measles levels of infectiousness.

This isn't the first virus that's operating globally in a vaccinated population - polio and smallpox didn't respond to vaccination by escaping it. Is there something special about Covid-19 that will make it the first global virus with enough power of self-improvement to keep getting better and better as it goes up the Greek alphabet?
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Re: New Covid Variants

Post by Turdly » Wed Jul 07, 2021 12:11 pm

lpm wrote:
Tue Jul 06, 2021 3:07 pm
polio and smallpox didn't respond to vaccination by escaping it
Smallpox is a double-stranded DNA virus and therefore has very low mutation rates so (relatively) slow evolution.

Poliovirus is a single-stranded RNA so has very high mutation rates. The oral vaccine contained live-attenuated versions of the three known serotypes so was effective against them all hence it was very effective (serotypes 2 and 3 are considered eradicated). However, vaccine-derived poliovirus exists due to the attenuated virus mutating to remove the deleterious genes.
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bob sterman
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Re: New Covid Variants

Post by bob sterman » Wed Jul 07, 2021 12:22 pm

lpm wrote:
Tue Jul 06, 2021 3:07 pm
Evolutionary fitness isn't infinite. Most changes to the RNA are irrelevant. Surely it can't be that all viruses run through potential configurations and pick out the best each time - original defeated by Alpha, Alpha defeated by Delta, eventually Delta defeated by Zeta and Zeta defeated by Lambda until the end of time...? Otherwise viruses would all trend to measles levels of infectiousness.
Viral fitness depends on context - environmental conditions, host genotype, host immune responses - and there are many trade-offs - so the process doesn't need to run in one direction. And there need not be consistent transitivity.

E.g. Sigma might outcompete Rho, and Tau might outcompete Sigma, but Rho might then do pretty well in a population with high levels of immunity to Tau (immunity which might generalise to Sigma but not to Rho). i.e. it can all get a bit "rock, paper, scissors".

What the Red Queen analogy doesn't emphasise that well, is that both pathogen and host can end up running in circles. Although this is perhaps more relevant where the host generation times are shorter - so we're talking about heritable qualities of pathogen and host.

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Re: New Covid Variants

Post by Bird on a Fire » Wed Jul 07, 2021 12:42 pm

IIRC one of the textbook examples of this is the Myxoma virus, which goes through cycles of high- and low-virulence strains depending on the size of the local rabbit population and whichever resistance genes are prevalent. And there are multiple genetic routes to similar phenotypic outcomes.

Rabbits tend not to fly all over the world, though.
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Re: New Covid Variants

Post by lpm » Wed Jul 07, 2021 1:26 pm

Brits don't fly all over the world these days either.
bob sterman wrote:
Wed Jul 07, 2021 12:22 pm
Viral fitness depends on context - environmental conditions, host genotype, host immune responses - and there are many trade-offs - so the process doesn't need to run in one direction. And there need not be consistent transitivity.
In late April 2021 the UK was 99% Alpha.

By late June 2021 Alpha had been replaced and it was 99% Delta.

To me, a casual observer, this doesn't look like ebb and flow, where different things trade off and the balance shifts. Alpha took the world by storm previously, but now Delta comes across as an unstoppable force, guaranteed to turn the world 99% Delta.

I think what I'm ultimately struggling with is why the 1918-19 virus was a great global winner, at R=4, and yet the world settled down again to our range of seasonal flus, at say R=1.5. Why should a world beater turn ordinary?
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Re: New Covid Variants

Post by jdc » Wed Jul 07, 2021 7:24 pm

lpm wrote:
Wed Jul 07, 2021 1:26 pm
Brits don't fly all over the world these days either.
bob sterman wrote:
Wed Jul 07, 2021 12:22 pm
Viral fitness depends on context - environmental conditions, host genotype, host immune responses - and there are many trade-offs - so the process doesn't need to run in one direction. And there need not be consistent transitivity.
In late April 2021 the UK was 99% Alpha.

By late June 2021 Alpha had been replaced and it was 99% Delta.

To me, a casual observer, this doesn't look like ebb and flow, where different things trade off and the balance shifts. Alpha took the world by storm previously, but now Delta comes across as an unstoppable force, guaranteed to turn the world 99% Delta.

I think what I'm ultimately struggling with is why the 1918-19 virus was a great global winner, at R=4, and yet the world settled down again to our range of seasonal flus, at say R=1.5. Why should a world beater turn ordinary?
This https://en.wikipedia.org/wiki/Spanish_f ... _pandemics reckons R was 1.8 for the 1918 virus and 33-56% of the world population was infected; herd immunity threshold would be 45% ish if R was 1.8 so maybe the virus hit enough dead ends to run out of available hosts?

Article also says some there was a "severe climate anomaly that impacted Europe from 1914 to 1919, with several environmental indicators directly influencing the severity and spread of the Spanish flu pandemic" so maybe once the climate was less anomalous that had an impact?

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Re: New Covid Variants

Post by bob sterman » Thu Jul 08, 2021 7:24 am

lpm wrote:
Wed Jul 07, 2021 1:26 pm
To me, a casual observer, this doesn't look like ebb and flow, where different things trade off and the balance shifts. Alpha took the world by storm previously, but now Delta comes across as an unstoppable force, guaranteed to turn the world 99% Delta.
Yes things will look directional over short time periods. The Red Queen cycling process is most relevant over evolutionary time for both pathogen and host - i.e. over many generations of each with pathogen and host genotypes changing.

However, vaccination programmes might create situations analogous to host genotype changes, creating populations less susceptible to particular variants at particular times. If vaccine induced immunity wanes over time we could end up running round in circles.

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Re: New Covid Variants

Post by raven » Thu Jul 08, 2021 8:00 pm

lpm wrote:
Wed Jul 07, 2021 1:26 pm
I think what I'm ultimately struggling with is why the 1918-19 virus was a great global winner, at R=4, and yet the world settled down again to our range of seasonal flus, at say R=1.5. Why should a world beater turn ordinary?
Well, you sort of get ebbs and flows with 'flu, in that most of the time you have not-too-bad seasonal flus running in the background, but then sporadic epidemics of more successful strains. The 1889-90 one, Spanish in 1918-20, Asian in1957/58, HongKong in'68/69, possibly a Russian one in '77-79, then that swine flu one in 2009.

And iirc, 1918 was milder in the early spring wave, fiercer in the autumn wave that year. There's a theory that was because soldiers who were very sick got moved to field hospitals, so that facilitated the spread of more virulent strains - or, if you want to look at it in terms of selection pressure, keeping mild cases on the front gave the virus an incentive to become less mild so it could reach more hosts.*

There's another theory, of course, that a bigger factor was terrible conditions in the trenches and general ill health & poor conditions across Europe at the time.

(*I'm sure I've seen it argued that we created similar pressures with Covid by isolating mild cases at home, but it's hard to stop hospitals becoming a source of transmission.)

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Re: New Covid Variants

Post by Stranger Mouse » Thu Jul 08, 2021 8:18 pm

raven wrote:
Tue Jul 06, 2021 1:45 pm
hakwright wrote:
Mon Jul 05, 2021 12:26 pm
Delta is taking over in many EU countries, as we knew would happen. The fact it is happening in the middle of summer, with lots of fresh air and mostly outdoor interactions, just shows how easily it can be transmitted compared to Alpha.
That one of Bojo's reasons for complete unlocking on the 19th, wasn't it. That we need to get the spike out of the way now, in late summer, so we can be done with it by winter so we don't hit flu season/NHS peak demand.

Vaccinated population vs Delta is like unvaccinated vs wild strain
Certainly seems like it from the UK data. We've got 9 day doubling atm.

(I'm assuming vaccines that reduce transmission would increase doubling times. But do Pfizer et al do that, or do they just reduce severity? In fact, thinking about it, if they increase the fraction of cases that are asymptomatic that alone might increase transimission just because people won't know to isolate.... )
Heard one theory for the Johnson strategy that they are running out of Pfizer for relative youngsters and AZ has the (overblown) blood clot issue for that age group so they are doing all this while they can still keep the public on their side by repeatedly shouting “vaccines!”

Sounds a bit far fetched though
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Re: New Covid Variants

Post by Woodchopper » Fri Jul 09, 2021 4:35 am

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization
https://www.nature.com/articles/s41586-021-03777-9

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Re: New Covid Variants

Post by bob sterman » Fri Jul 09, 2021 7:01 am

Stranger Mouse wrote:
Thu Jul 08, 2021 8:18 pm
Heard one theory for the Johnson strategy that they are running out of Pfizer for relative youngsters and AZ has the (overblown) blood clot issue for that age group so they are doing all this while they can still keep the public on their side by repeatedly shouting “vaccines!”

Sounds a bit far fetched though
Well it's true that with higher case numbers the risk benefit ratio shifts for the AZ jab - favouring its administration to younger age groups!!

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Re: New Covid Variants

Post by Woodchopper » Fri Jul 09, 2021 8:30 pm


The investigation on daily sequential PCR testing of the quarantined subjects indicated the viral load of the first positive test of Delta infections was ~1000 times higher than that of the 19A/19B strains infections back in the initial epidemic wave of 2020, suggesting the potential faster viral replication rate and more infectiousness of the Delta variant at the early stage of the infection.
https://virological.org/t/viral-infecti ... ariant/724


Fairly small sample though.

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Re: New Covid Variants

Post by Woodchopper » Sat Jul 10, 2021 1:41 pm

Cases have shot up in the Netherlands.

On 30 June there were 643 cases, on 9 July there were 6 986.
https://coronadashboard.government.nl/l ... ste-mensen

Case growth being driven by people aged between 10 and 30.

In response the Netherlands has reimposed some Covid restrictions:
https://www.reuters.com/world/europe/ne ... 021-07-09/

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Re: New Covid Variants

Post by Herainestold » Sat Jul 10, 2021 3:41 pm

Woodchopper wrote:
Fri Jul 09, 2021 8:30 pm

The investigation on daily sequential PCR testing of the quarantined subjects indicated the viral load of the first positive test of Delta infections was ~1000 times higher than that of the 19A/19B strains infections back in the initial epidemic wave of 2020, suggesting the potential faster viral replication rate and more infectiousness of the Delta variant at the early stage of the infection.
https://virological.org/t/viral-infecti ... ariant/724


Fairly small sample though.
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Delta changes everything.

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Re: New Covid Variants

Post by Woodchopper » Sat Jul 10, 2021 9:11 pm

Woodchopper wrote:
Sat Jul 10, 2021 1:41 pm
Cases have shot up in the Netherlands.

On 30 June there were 643 cases, on 9 July there were 6 986.
https://coronadashboard.government.nl/l ... ste-mensen

Case growth being driven by people aged between 10 and 30.

In response the Netherlands has reimposed some Covid restrictions:
https://www.reuters.com/world/europe/ne ... 021-07-09/
And 10 345 cases today.

The Netherlands only has a population of 17 million compared to 66 million in the UK. Scale up for population and the Netherlands cases are the equivalent of 40 000 per day.

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Re: New Covid Variants

Post by Herainestold » Sun Jul 11, 2021 12:36 am

Woodchopper wrote:
Sat Jul 10, 2021 9:11 pm
Woodchopper wrote:
Sat Jul 10, 2021 1:41 pm
Cases have shot up in the Netherlands.

On 30 June there were 643 cases, on 9 July there were 6 986.
https://coronadashboard.government.nl/l ... ste-mensen

Case growth being driven by people aged between 10 and 30.

In response the Netherlands has reimposed some Covid restrictions:
https://www.reuters.com/world/europe/ne ... 021-07-09/
And 10 345 cases today.

The Netherlands only has a population of 17 million compared to 66 million in the UK. Scale up for population and the Netherlands cases are the equivalent of 40 000 per day.
I hope the Dutch NHS has lots of oxygen. They are going to need it.
Delta changes everything.

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Re: New Covid Variants

Post by shpalman » Sun Jul 11, 2021 10:22 am

molto tricky

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Re: New Covid Variants

Post by shpalman » Mon Jul 12, 2021 7:15 pm

Woodchopper wrote:
Sat Jul 10, 2021 9:11 pm
Woodchopper wrote:
Sat Jul 10, 2021 1:41 pm
Cases have shot up in the Netherlands.

On 30 June there were 643 cases, on 9 July there were 6 986.
https://coronadashboard.government.nl/l ... ste-mensen

Case growth being driven by people aged between 10 and 30.

In response the Netherlands has reimposed some Covid restrictions:
https://www.reuters.com/world/europe/ne ... 021-07-09/
And 10 345 cases today.

The Netherlands only has a population of 17 million compared to 66 million in the UK. Scale up for population and the Netherlands cases are the equivalent of 40 000 per day.

Dutch PM Rutte 'sorry for easing restrictions too soon'
molto tricky

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