Thread by @PatrickSSte

THREAD (quite long - sorry!)

IMO you can’t understand CoV-2 or any other virus without understanding the "virulence-transmission trade-off hypothesis"

This hypothesis was introduced in the 1950s to explain observations of myxomatosis. Basically, very mild strains became moderate, while very virulent ones also became moderate

cambridge.org/core/journals/…

The hypothesis says a virus must balance the amount of shedding against the time during which the shedding takes place – the time will be reduced if viral virulence is too great

This is often quoted as saying a virus mustn’t KILL its host too quickly. This is appropriate for myxomatosis and other insect-borne viruses, but not for respiratory viruses

In the case of resp-virs, selection dictates that the virus also shouldn’t IMMOBILIZE its host, because then the virus would be less likely to reach another potential host

Hence our hypothesis - @julialbach's & mine - that resp-virs use TEMPERATURE to stay in the nose and throat

Insect-borne viruses can be spread by insects even if the host is at death’s door and completely immobile.

Hence insect-borne viruses tend to be more pathogenic p < 0.0005

doi.org/10.1146/annure…

Now here's the strange part. Biologists are taught about the virulence-transmission trade-off hypothesis at uni, but many don’t seem to believe it

Many virologists on Twitter & elsewhere talk as though viruses are always trying to overcome our defences & kill us as quick as poss

We (@julialbach and I) believe this is completely wrong.

If it were true many viruses would be worse than Ebola and stable multicellular life-forms would be impossible (in our opinion, well, mine anyway)

In reality the viruses don’t try to attack us too hard. They MODERATE their pathogenicity.

Quite quickly

How quickly?

Well, we often see a surge of colds in autumn. The only rational explanation that I know is the one by @julialbach and me: the virus loses thermal sensitivity over the summer, and becomes INTRINSICALLY (though not apparently, because weather is warm) more virulent

(It has to do this, cause otherwise it couldn't spread in the warm weather)

So this thermal adaptation takes place over a few months, maybe weeks

The only person I’ve seen on Twitter putting forward the trade-off hypothesis (though he doesn’t call it that) in the context of Covid is @mattwridley. He correctly (IMO) highlights hospital transmission, but at this stage in the pandemic it seems unlikely they’re so important

So, we now need to look at the effects of our behaviour, and our governments’. The UK 10-day "ping" self-isolation periods may be particularly harmful because they can completely block the milder, long-incubation strains, which I'd expect to be much more apparent by now

(Viral strains strongly compete against each other, because whichever one infects a particular host FIRST generates immunity that stops subsequent strains for a while)

Most scientists talk about each strain as though it’s pretty constant – e.g. they ask, “how sick does Delta make us in comparison to other strains?”

In other words, they don’t realise that we’re continually driving the virulence of Delta either upwards or downwards

Another unfortunate feature of current thinking is that scientists focus in particular on the sequence of the spike protein.

This is probably because it’s EASY to look at protein sequences

@julialbach & I suggest almost all resp viruses use thermal sensitivity in particular to moderate pathogenicity. This has an important advantage – virus can stay in nose & throat, and use built-in transmission mechanisms: coughing, sneezing & runny noses

So what should scientists focus on?

(1) Incubation periods

(2) The RNA secondary structure of the virus, which is intrinsically thermally sensitive

References in our paper

doi.org/10.1002/rmv.22…

Video if you prefer

Putting it another way - I discussed this with Ron Eccles when my first paper came out

doi.org/10.1002/rmv.21…

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