Thread by @SGriffin_Lab

OK, an attempt to explain virus evolution, especially SARS2, and how our present situation influences this process.
TLDR...it's fair to say that current UK scenario is almost certainly an "enabler" for SARS2, and it could encourage the refinement of, or next step from Delta...

Some important points to remember:
1. Viruses are obligate parasites, so entirely dependent upon the host to survive and thrive.
2. Viruses are the ultimate embodiment of "selfish genes".
3. Viruses usually evolve towards improved transmission, in the absence of interventions.

4. Mutation is essentially a random process, but selection and establishment of new mutants is not.
5. We're talking about Darwinian evolution, but on a massive and incredibly fast scale. Nevertheless, "fitness" and evolutionary niches are major players.
6. 1-5 = too much jargon!

So, how to conceptualise and visualise this stuff?

How's about this...

Bear with me...

Now, I'm certainly not saying that the generation of mutants/variants is entirely random, but there's certainly an element.
For RNA viruses (and others, indeed to an extent this occurs in every genome), the process of genome replication occurs with a greater or lesser degree of

error. Some viruses, such as hepatitis C virus, dengue, etc, this error rate is extremely high, but it varies, and for DNA viruses such as herpesvirus it's very low indeed, much more on the scale of our own DNA.
This actually reflects different evolutionary strategies, and there

are successful examples of both.
However, Coronaviruses such as SARS2, have sometimes been labelled as slow mutators...and yet we are seeing huge variability. Indeed, the virus actually makes its own "proofreading" enzyme that double checks the replication process.
However, as I

mentioned, this process isn't entirely random, because for a mutation to exist in nature, it not only has to occur, randomly, it has to become established...and here's where Darwin comes into play, but in a vastly accelerated microcosm.
So, for this to occur, certain criteria are

to be met:
1. The change mustn't be overly deleterious to the part of the genome in which it occurs. This could be a coding region (ie part of the message for a protein), or there are structural and/or regulatory elements in the RNA genome that are essential. Thus, you find that

mutations are more likely to occur in some places than others. You could equate this to removing some of the balls from the lottery machine, and perhaps adding in extra for other numbers. Some viruses use this as a deliberate strategy, with certain less important regions having

many of the same balls, serving as a deliberate distraction to the immune response. Its not that "bad" changes don't occur, but the render the virus less "fit", so it's unable to compete...unless circumstances change (see below)
2. The change needs to either be neutral or ideally

favourable in terms of the virus' level of fitness. This in turn is dictated by the environment the virus finds itself in...the "pressures" in this environment that dictate the Ts&Cs can involve immunity, drugs, npi's, numbers of susceptible lungs etc...
3. The pressures are both

dynamic and interactive, so the combination of mutations that will successfully adapt and allow the virus to be successful also need to occur in concert. This is a bit like using one lotto machine to draw the winning numbers on the ticket, and the virus having another...
4. We

can influence the conditions on the winning ticket by implementing control measures, vaccines etc, literally adding more numbers necessary for a win...of course, these can be taken away as well...
5. It's also the case that our immunity etc means that a more dramatic, potentially

more deleterious change is required for the virus to adapt...
6. It may seem that we're setting the virus an impossible task, but the game is actually much more in the balance. First, the virus gets more than one go, and it's also allowed to keep the changes that work much of the

time, and keep trying for the others...
7. For this reason, our "variants" of concern aren't the consequences of one, or even a handful of changes, they have accumulated many, building and improving on last week's winning combination. Moreover, the severity of changes required to

win seems to be something SARS2 proteins appear very capable to deal with. We see quite profound changes in spike for example, such as switching an acidic to a basic amino acid. This may not sound that important, but if you consider that the structure and function of spike needs

hundreds of amino acids to act in concert, as well as buddying up into a trio, this sort of change is important. This is one reason that we are concerned about VOC in relation to immunity as such changes can render potent antibodies useless...if you compare to e.g. measles, this

virus lacks the structural flexibility, or "plasticity" to tolerate such changes, and we've been able to use the same vaccine for decades as a result. As such, VOC result from, and give rise to, lineages of SARS2 that continue to evolve.
8. The virus also gets to take multiple

turns to pick out winning balls, and it also has a massive array of machines it can continue to pick them from because of the very high levels of infection - an obligate parasite needs a host.
9. In turn, the way in which each lotto machine is set up in terms of winning and virus

balls (where am I going here?!), the number of picks, and the frequency new balls are selected depends very much upon our behaviour. As well as the intrinsic factors that dictate the outcome of virus meets host, exposure levels and frequency matter. Clean air, masks, distance and

mixing/travel all affect the number of times the lotto machine operator presses the button. Changes in transmissibility also matter.
10. Similarly, when we loosen restrictions we expect cases to increase and the ratio for the number of balls picked versus the number needed to win

tilts back in favour of the virus.
11. If this wasn't hard enough, the virus has other tricks. First, there are some balls that, if picked, actually allow it to access a whole bunch of extra balls, possibly an extra machine. This is because such changes compensate for the bad

aspects of other changes, so the virus gains hitherto unreachable benefits, the price of which used to knacker it completely. In addition, the virus can sometimes tear up it's ticket and sellotape it to a ticket from one of its mates, potentially generating an entirely new combo.

This is known as recombination...a rare event so far for SARS2, but certainly happens in other CoVs...
12. So what happens in the long run? Well, conceivably you could get cycles lasting forever where virus and host alternate between escape and control, exponential growth as a

result of R going above or below 1. This is generally what has been happening for the last 2 years across the planet.
One thing that viruses DON'T generally do is become less virulent. The virus doesn't change, we do. You see this for example in areas where measles vax rates

drop...
Eventually though, what most virologists and epidemiologists envisage is that we will reach a point, at least in some countries, where the virus becomes endemic...
13 (or 12?!). So, what does endemic mean? It seems to have become a favourite term for a lot of folks, in

particular those trying to say we should just ignore this virus from now on...a bit like...

What endemic means us that a virus persists within a population independent of external influences, mainly, because the combination of its ability to transmit and the inherent immunity in the population, or, more importantly, the number of susceptible hosts in the population

means that R = pretty much one all the time, with occasional flurries and outbreaks. Chickenpox is endemic in the for example, Crimean Congo Haemorrhagic Fever virus, isn't...😉
14. So, are we there? No. The virus is still changing, our immunity is incomplete, even waning in some

quarters, and we have nothing to help us beyond the good will of a not inconsiderable portion of the right-thinking UK population...as a result, exponential growth still happens.
15. Thankfully, our amazing vaccines are reducing the consequences of infection in terms of severe

disease, but not completely, plus our susceptible population now comprises younger people, waning vaccinees and those who choose not to protect themselves. This still provides ample pairs of lungs for the virus to infect, and ultimately start picking balls out again.
16. So, the

question really is how quickly do we want to reach endemicity, and how much harm and how many cycles of epidemic waves so we want to endure along the way? Much like not taking the whole packet of antibiotics, we are at present not setting a very tough task for the virus as we let

it run amock, but there's still enough of a challenge for it to keep producing new balls of its own...(it's different to antibiotics in the sense it is multi step and at the population level rather than individually, but a useful comparison before anyone jumps on that!). As such

the mix of high prevalence, partial immunity and a hodge podge of restrictions really does represent a massive churn, within which the chances of the virus producing a winning ticket really do increase by more than certainly I am comfortable with. Notwithstanding the harm that is

visited upon those unfortunate enough to still succumb to this dreadful infection, those who develop long COVID, or those CEV who have officially or unofficially shielded for 2 years to enable pubs to open...(glib statement alert, of course I have sympathy for industry and jobs).

17. Our vaccines provide a way to accelerate progres towards what inhope will eventually become endemic SARS2 at VERY low levels that can be easily contained. BUT, we cannot assume that the path towards this equilibrium will be easy, and that we won't see changes in the virus,

nevermind the difficulties and uncertainty around present strains, that really cause us extreme problems again that damage society. This virus causes widespread damage to organs and the vasculature that we still don't know how to deal with, and this continues to claim lives every

day.
18. So, why have I waffled so much? Well, the giant chickenpox party for SARS2 in schools, entering a vaccine booster race, lack of restrictions and poisonous antivax morons are both shameful and unwise in equal measure. We MUST both safeguard our population from 50k deaths

and profound morbidity every year for the foreseeable future, whilst at the same time we must also think long term towards that future where normality can actually be achieved without sacrificing those least able to "crack on"...
19. Please, those considering next steps, look to

the future, make the road as few years as possible and reduce the harm along the way. Increase vaccines whilst reducing cases yo tip the balance back in our favour, don't use partial measures, don't underestimate SARS2 and certainly sort out schools and stop using kids as live

deliberate SARS2 parties. Apply the precautionary principle and we'll all eventually get what we want, rid of this nasty critter, freedom to live and the economy and country back on track, hopefully minus the bitter divisions we're seeing at present.

Apologies, way too long!