## New variants

There’s a new variant of cov-19, the UK strain, that is something like 70% more infectious than previous strains. At this point its lethality seems about the same as earlier strains.

Virologists, most of them, did not expect this.  I did.

Let’s consider some simple examples. Imagine that you have someone – a single individual – with what we will call a normal strain, A. On average, in  the current situation,  it has an R0 well above 1.

What is the most likely outcome? Most likely, he doesn’t spread it to anyone, and it dies out.  Overdispersion: most people don’t do much spreading, and a few do a lot. Let’s say that 20% of those infected do all of the spreading.  Right off the bat, 80% of new strains die out, just because of this pattern.

Now, imagine that we simultaneously introduce two new strains, A  and B with a 50% greater R0%.  for each, a single individual.

There are four possible outcomes: A spreads widely, B spreads widely, both and A & B spread widely , both A and B disappear.

Most likely both will disappear (~64% chance) .

There’s a fair chance that A will spread while B is lost, and a moderately larger chance that B will spread while A is lost.

There is essentially zero chance that both will spread widely: even if both manage to avoid being lost by chance in the beginning, B will grow faster than A and replace it.

So, suppose you introduce one person with A, and one person with strain B: can you judge the relatively infectivity by which one succeeds?  No – there’s a significant  chance that the less-infective one will win out.

Now consider a situation in which A is already common, and a single case of B  is introduced.  what are the possible outcomes?

1.  B is lost by chance.  ( > 80% probability)

2.  B replaces A – happens if B is lucky enough to get past the risk of extinction when rare.  But once it gets up to a few hundred copies, it will surely replace A.

What can we conclude if B is rapidly replacing A ( as has been the case with the new UK strain)?

That it surely has significantly higher transmission, significantly higher R0.

Many virologists thought this very unlikely, and some said that you could never know that a new variety had higher transmission from mere incidence data: you must understand the biological mechanism.  Are they correct?  Obviously not.

Why did they think that a new, more transmissible variant of COVid-19 was unlikely?  I would say there are several reasons. One, they typically deal with viruses that have been around for a long time, like measles ( > 1000 years) .  An old virus is going to be pretty well-adapted to to humans.  Probably it’s at a local optimum, where small changes would reduce infectivity. But you don’t expect that high degree of optimization in  a virus that’s brand new in humans: while spreading to very many people, more than 100 million,  greatly increases the chance of  transmission-increasing mutations.  Fisherian acceleration.

Like most biologists and MDs, most virologists don’t know any theory, and in fact don’t _believe_ in theory.   For this they occasionally pay a price.

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### 39 Responses to New variants

1. pyrrhus says:

Episode 1,000,001 of the fascinating drama “Why Ignorance Kills”…..

2. pauljaminet says:

Spiritual history:

PH MANIFESTO: Was this a natural evolution (higher infectivity, lower lethality) or was a better engineered vaccine-like virus introduced to end the pandemic?

• teageegeepea says:

How would this new variant “end the pandemic”?

• Failure says:

It would end it for all practical purposes if it 1) spread much faster than the regular strain 2) made hosts immune to the regular strain 3) were much less lethal. I don’t think 3 applies though.

• Barry O'Bamaugh says:

If you could get a much more contagious strain with lower virulence while still generating antibodies effective against all circulating WuFlu strains then you have a self-replicating vaccine, if you squint. I’m not aware of any compelling evidence that the new strains are significantly less dangerous than “Vanilla” Sars-Cov-2 but maybe I’ll be pleasantly surprised.

3. jb says:

There is an interesting article in the New York Times concerning a possible endgame for the virus: The Future of the Coronavirus? An Annoying Childhood Infection. The idea is that the virus will become harmlessly endemic in young children, who will then be able to shrug off reinfection later as adults. I.e., Covid-19 will simply become a fifth coronavirus related common cold. (Indeed, the article raises the possibility that one of the four previously endemic coronaviruses was introduced in 1890 and caused a serious pandemic back then, before settling down and becoming inconsequential today).

I suggested almost exactly the same idea last March, but you thought it was “totally stupid”, which seemed a bit harsh. So I’m wondering now if you have any new thoughts about this possibility.

• teageegeepea says:

He said “it is quite possible that some or all of those coronaviruses were more lethal when they first showed up, but why would that mean that we shouldn’t try to stop something bad happening now? When we almost certainly can?” so it doesn’t actually sound like he’s contradicting the NYT, however much he would normally like to do so.

4. ralph says:

obvious questions:
1) do antibodies (existing immunity) against older strains work for the new strain?
2) do vaccines currently available work for the new strain?
if the answer to these is “yes” – we’ll survive

• epoch says:

Depends on how you define “we”. If it is you and I we won’t survive, virus or not.

5. JayMan says:

On top of the British variant, which itself is really bad news due to its increase contagiousness, there is the new South Africa variant which may be twice as contagious as previous strains and may have at least partially escaped immunity conferred by previous strains (Estimates of severity and transmissibility of novel South Africa SARS-CoV-2 variant 501Y.V2).

Also a new Brazilian strain which might have also escaped immunity (Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil

6. A caveat:

It is possible, though unlikely, for both strains to spread widely. For full replacement, you need to bring the Rt of the slower-growing strain down below 1 for long enough that it disappears, while the Rt of the faster-growing strain stays above 1. That depends on the effectiveness of the infection controls where this is happening. If they’re so crummy that both the original and new strains have Rt above 1, then they can both fix and grow big (though the faster-growing strain is more likely to fix). The prevalence of strain B still grows very rapidly (that’s independent of the instantiated Rt), but strain A will still be growing. In practice, most western countries have been stupidly trying to keep the Rt floating right around 1, optimal conditions for encouraging strain replacement.

Why would one of the new mutations be more likely to spread than the other one if they had the same level of transmissibility?

• swampr says:

“A and B with a 50% greater R0%” sounds ambiguous to me but it’s clear from the rest he means only B has a greater R0.

• gcochran9 says:

Evidently I could have stated it more clearly, but by assumption B has a a 50% greater R0 than A.

OK, I see what you meant, thanks for the reply.

8. Yudi says:

“Where there is no vision, the people perish.”

9. magusjanus says:

” For this they occasionally pay a price.”

I was in 100% agreement until that last line. Turns out they don’t pay a price. We do. They continue to do just fine. I doubt there will be much of any personnel changes at upper echelons of FDA, CDC, WHO, etc. despite the death toll of their incompetence likely ending up being in the millions. Much like the Iraq war pushers, or the Arab Spring idiots, they’ll do just fine.

• Well, some of them will die.

• CurlyWurly says:

The word “occasionaly” does a lot of heavy lifting in that quoted sentence.

10. Rob says:

What is behind biologists and well, the entire cultural elite, ‘believing’ evolution is true, but not believing any of the things that follow inexorably from evolution by natural selection?

Do they think life evolved, past tense, and is now done? I could see that. Almost all obvious mutations are detrimental, though there are more big obvious mutations in an evolutionarily novel situation. You can’t see subtle mutations, most of which are also detrimental. Also, most smartish people think intelligence is most evolved thing about man, and the less intelligent have more kids.

Do they not understand what evolution by natural selection means, but just know that it’s the accepted scientific theory? Sort of like I know Maxwell’s theory of electromagnetism is the accepted classical theory, but can’t tell you any laws or work out how to build a motor? I know there’s a quantum theory of electromagnetism that is now the true one. But unlike physics, basic understanding of evolution does not require any math for a layman to be able to make some predictions. I can see how people who don’t know anything about proteins or cellular biology might not be able to gauge what is possible. Biologists don’t have that excuse.

Is it a mental crimestop thing? You start taking evolution seriously. Then you think that some sex differences must have evolved. Then you start wondering if differences in intelligence could be genetic. Then you start wondering if any racial differences could be evolved. Suddenly, you realize that The Dreaded Out-Group thinks those things, and if you say any of them, then you will lose your job, etc. Crimestop kicks in, and pretty soon you can’t think of any consequences of evolution being true.

Maybe they don’t know anything at all about variation and selection being the mechanisms of evolution, but just know that everything has a common ancestor back far enough, so evolution is just a club to beat the stupid Christians with? This I could see as well.

But do any of these apply to viral evolution?

• Petja Ylitalo says:

What is behind biologists and well, the entire cultural elite, ‘believing’ evolution is true, but not believing any of the things that follow inexorably from evolution by natural selection?”

Most people learn most theory as question-answer pairs. This enables them to give right answers when someone (usually teacher) asks them something. It does not enable them to make any deduction from these.
This is in no way restricted to subjects close to crimethink.

For example, people learn that inflammation is an immune reaction to invaders in your body. People learn that vaccines work by giving your immune system parasites to practice with.
90% of doctors will not make the connection that recommending anti-inflammatory medicine to take away “side effects” of vaccination is a bad idea.
Or that anti-inflammatory medicine might cause your body to work well in resisting infections in general.

• Curle says:

I hope you are a teacher of some kind. This is a great explanation.

• Joe says:

I’m not seeing how the last statement follows from the ones before – why would reducing your body’s inflammatory response cause it to work well in resisting becoming infected?

• random observer says:

I read that as a typo, thinking it should read “work less well”. I’m open to the idea I have misunderstood something.

• Petja Ylitalo says:

Should indeed be “work less well”

• Joe says:

Thank you.

• dearieme says:

“Most people learn most theory as question-answer pairs. This enables them to give right answers when someone (usually teacher) asks them something. It does not enable them to make any deduction from these.”

The art of setting worthwhile examinations involves devising questions that defeat such people.

• Petja Ylitalo says:

Problem is, schools and students are scored on how good test scores their students get.
If a teachers wants to get their students to really understand the material, his students will have lower test scores than those teachers who just teach what to answer on next test
This can lead to that the more you evaluate your school and teacher performance, the less they actually learn.

You could prevent this by testing students at random times without pre-warning, ½ year to 3 years after the course has ended, but that would give a very bad impression of how much your schooling system actually manages to teach, so no-one has incentives to do that either.

11. Rob says:

Random questions for Greg:

Do you think COVID is an accidental(?) release from the lab in Wuhan?

Any ideas on what the English Sweat was? Is there any chance we could find it in a grave?

Have you seen virscan or phage immunoprecipitation sequencing using displayed human or microbe antigens against someones’s antibodies? It seems like something that might give clues if an infection causes homosexuality. Maybe do phage immunoprecipitation of phage displaying antigens on antibodies from identical twins who are discordant for being gay. If the gay twins have antibodies for some epitope of protein x, then that points to a possible cause of homosexuality.There is a conceptually similar way to find what antigens T cells recognize, though as far as I know it is only for MHCII.

It seems to me virscan/phageIP-seq could be used to create the antigen equivalent of GWAS, where traits are correlated with what epitopes subjects have antibodies against instead of their SNPs. Like not just do gay/straight twin pairs, but try to discover if having antibodies for various things correlated with IQ or obesity. If I remember correctly, your Atlantic magazine article about infections causing chronic diseases mentioned a virus that causes weight gain in chickens. Fat/thin sibling pairs could be tested for antibodies to that bound that virus, plus many more.

Here is the(?) virscan paper. https://science.sciencemag.org/content/348/6239/aaa0698.full

There are a way to display whole proteins on viral capsids, so one could see if gay/straight twin pairs were discordant

Do you think COVID is an accidental(?) release from the lab in Wuhan?

Any ideas on what the English Sweat was? Is there any chance we could find it in a grave?

Actually on topic:

Could having an r_o > 1 but still small be worse than a higher r_o? At the extremes, if one dude catches a coronavirus, and then infects everyone in the world directly (dude gets around), then the virus has no chance to evolve. If everyone who gets it gives it to exactly 1 person every time, no exceptions, then the virus has lots of chances to evolve to more infectious variant, though there are not a lot of virus genomes, so evolution might take a long time to come up with a more infectious version.

• gcochran9 says:

Do you think COVID is an accidental(?) release from the lab in Wuhan? < I don’t know.>

Any ideas on what the English Sweat was? (< not really> Is there any chance we could find it in a grave? < yes.>

• Rob says:

What we about a GWAS equivalent for antibodies to various chunks of microbe proteins correlating with traits. Like a good test might be to see if an antigen panel that included strep could be correlated with rheumatic heart, or whatever it is called. Some accepted infection-later/chronic disease link.

Could go a long way towards proving the Cochran/Ewald new germ theory of disease. Even if one accepts the theory, I can’t think of another way to do hypothesis generation for causes and effects that can be separated by decades. Especially for something like PANDAS, if you believe PANDAS is real, where the cause may not be ‘strep’, but particular strains of strep that might not even serotypes.

12. Ilya says:

Yes, you’re right 95+% of the time (other than the renown Indo-Euro mampire theory, maybe).

So, further, based on theory, it seems now that the requirement on how wide the vaccination efforts have to go to vanquish the virus — it just went from around 66% of the population to 80%!

13. Jonathan Small says:

Until 2020, the British “National Institute of Clinical Excellence” (NICE) would not approve treatments which cost more than £30,000 per quality adjusted year of life added.

14. dearieme says:

“most virologists don’t know any theory”: the British government tried to get round this difficulty by consulting astrologers from Imperial College.

• dearieme says:

Note to our esteemed blogger: the Astrologer-Royal holds a Doctor of Philosophy degree in theoretical physics.

15. David Chamberlin says:

I once stated that Covid19 was likely to evolve to be less lethal and Cochran rightfully corrected me. It really doesn’t need to, it was ideally designed to spread easily right out of the gate with so many asymptomatic carriers of this infectious disease. Some diseases do evolve to become less lethal because it aids their spread but not Covid19.

• Rob says:

How could a disease evolve to be less virulent, Your bout of ‘the’ flu is not a singular thing. It is billions of ‘live’ virus genomes. It seems experimental infections are usually started with like a hundred thousand to a million pfu (plaque forming units). In a quick googling I could not find an estimate of the number of potentially infectious particles in a flu victim either at one time or over the course of the illness. Even if interhost infection would be higher for a less virulent genome, within host selection would almost certainly favor genomes that produced offspring faster – were more virulent.

An analogy would be family planning for fruit flies. It is nearly impossible to select fruit flies to control their population. In experiments where the population would do better producing fewer offspring, flies don’t limit their individual reproduction. They eat the eggs or offspring of other flies. (I read this in a popular science article. I did not read the paper). A virus genome that limits its reproduction just leaves uninfected cells for more fecund genomes.

Selection would favor genomes that can’t infect cells that will not spread to cells or tissues that cannot infect new hosts. That’s interhost selection. Interhost, a flu virus that infected say, brain tissue successfully would infect some neurons, the offspring of that virus would spread to more brain. When the host died, the neurotropic would die out.

I did see an experiment with a phage where 2 bacterial strains (A and B) each had a protein (Pa and Pb) that the virus bound and used to insert the genome into enter the cell, but the virus could only reproduce in strain A. After however long in culture, the virus evolved attachment protein versions that only bound Pa. Viruses that entered strain B were did not reproduce, so there was a selective advantage in only binding Pa.

Could the above scenario happen? Maybe, but the wild type phage in the scenario above bound both strains. In my brain flu example, there would be a slight interhost reproductive advantage to genomes that did not easily evolve neurotropism. But within host selection could easily lead to everyone infected with that flu dying from brain infection, despite interhost selection.

A virus evolving lower virulence is much more like fruit flies evolving family planning than like a virus evolving to prefer viable hosts.

• David Chamberlin says:

“How could a disease evolve to be less virulent?”
Easy. Think about it. It can spread more easily if it doesn’t kill you or put you on your back recovering.

16. Martin L. says:

I am obviously not Greg, but I wonder if the British Sweat (“Sudor Anglicus”) might have been a rickettsia. Those could follow summer rodent surges and are infamous for re-infecting/recrudescence and among other symptoms they cause extreme fever and sweating and a trance-like semiconscious state. Certainly, the ability to get reinfected suggests (doesn’t prove) that it was bacterial.

On the other hand the B.S. seems to have progressed and killed a lot faster than the rickettsiae we know do. My second best guess after rickettsial disease is that it was some sort of mosquito-borne blood parasite.

Speaking of which Greg, how likely is it IYO that COVID is capable of causing long-term/permanent/latent infection that never is cleared? I have a feeling a lot of the alleged COVID reinfections are actually this.