[Stabbsy]

Vaccine evasive variants are more likely to occur where vaccines induce suitable evolutionary pressure, so, um, here (the West/N hemisphere). The slower and less efficient a nation’s vaccine roll out, the more likely.
Obviously, at some point in the future, that pressure will move south as poorer countries extend their vaccine programs.

Struggling with this - seems to contradict itself. More variants occur where there's suitable evolutionary pressure and this pressure is higher where the vaccine rollout is slower? Care to explain?

I've heard this argument of evolving in response to "evolutionary pressure" a few times and I can't get it to sit well based on what I understand about evolution more generally. I think viruses sometimes mutate when they transmit, it's what they do. Question is, do they mutate in a "smart" way in response to evolutionary pressure or is it just that they mutate anyway and the ones that mutate to become more infectious become the most successful version while others die out? Think of it in terms of human evolution - we didn't/don't evolve in a "smart" way, that's the intelligent design hypothesis (or whatever it's called) and it's bollocks. We evolved by chance mutations that gave competitive advantage. Those with the mutation then out-competed the remainder over a very long period of time and there you have it - evolution.

Are we implying something different to this for viruses? Or is it just that timescales are that much shorter? I'd argue that the vaccines are not inducing "evolutionary pressure", but that mutations will happen anyway. If that's the case then the maths says that variants will most likely occur where transmission is highest and, if the vaccine reduces transmission, that will not be where vaccine take-up is highest.

Disclaimer : I'm not a biologist, so I could be way out. Someone with a better understanding of evolutionary biology, please correct me if I'm wrong.

[SA Chris]

Thanks, was going to ask the same. As I understand it mutations in nature occur and where the mutation happens to occur in an environment which allows that mutation to thrive, it exploits that environment and multiplies successfully. If it's not a conducive mutation, that strain just dies out.

Given that the vaccination is just reducing opportunities to transmit and this mutate, and no human body or external environment is any better or worse for it, how is it going to react to evolutionary pressure?

[Oldmanmatt]

At a guess and from badly remembering what I read...

A mutation, any mutation, can occur anywhere at any time, of course.

If a population develops or induces a sufficiently high level of immunity to the prevalent/existing strains quickly enough, it should suppress transmission, reduce cases and therefore the pool of potential mutation incubators. Even if some of those strains show some vaccine evasion.

Our vaccines currently require two doses, at a spacing greater than the incubation period of the virus, to be sufficiently effective to suppress transmission enough, that if the proportion of partially protected people is allowed to straggle out, alongside an unprotected population the risk of mutation remains higher, longer and the partially protected population (and their (likely) consequently reduced respect for transmission risk), provide a neat little petri dish for developing a pool of more evasive strains, because those are the ones that produce the symptoms in the partially protected, that increase spread so nicely.
There was something about this already being an issue with a disease that had so many asymptomatic and mildly affected carriers anyway (like the Flu), whereas things like Ebola, tend to kill people too quickly and uniformly, for this to be an issue (although, that might change now we have treatments and vaccines for Ebola).
I believe something similar happens/is more likely to happen with antibody treatments too and those have been way more prevalent in the First World too.

But, I’d love to know this is all wrong, especially given the slow pace of some Western nations vaccine programs.

[AJM]

Vaccine escape is just a mutation that means the immune system doesn't recognise the virus any more. Those mutations occur randomly the whole time. When noone is vaccinated, a vaccine escape mutation confers no benefit. When everyone is vaccinated, there's hopefully not enough of a pool of cases to support lots of mutation. Somewhere in the middle there's a "sweet spot" where there's a sufficient cases to give rise to mutations and a competitive advantage to being able to access the vaccinated hosts as well.

[Stabbsy]

At a guess and from badly remembering what I read...

A mutation, any mutation, can occur anywhere at any time, of course.

If a population develops or induces a sufficiently high level of immunity to the prevalent/existing strains quickly enough, it should suppress transmission, reduce cases and therefore the pool of potential mutation incubators. Even if some of those strains show some vaccine evasion.

Our vaccines currently require two doses, at a spacing greater than the incubation period of the virus, to be sufficiently effective to suppress transmission enough, that if the proportion of partially protected people is allowed to straggle out, alongside an unprotected population the risk of mutation remains higher, longer and the partially protected population (and their (likely) consequently reduced respect for transmission risk), provide a neat little petri dish for developing a pool of more evasive strains, because those are the ones that produce the symptoms in the partially protected, that increase spread so nicely.
There was something about this already being an issue with a disease that had so many asymptomatic and mildly affected carriers anyway (like the Flu), whereas things like Ebola, tend to kill people too quickly and uniformly, for this to be an issue (although, that might change now we have treatments and vaccines for Ebola).
I believe something similar happens/is more likely to happen with antibody treatments too and those have been way more prevalent in the First World too.

But, I’d love to know this is all wrong, especially given the slow pace of some Western nations vaccine programs.

Yes, I'm fine with most of that  - I think what you're saying there is that variants can still occur in a partially vaccinated population and that the more people you vaccinate the better. But that's not consistent with what your earlier post said, which was :
 

Vaccine evasive variants are more likely to occur where vaccines induce suitable evolutionary pressure, so, um, here (the West/N hemisphere).

The key point is that the vaccine is not inducing the variants, it's all just chance. The same mutation is just as likely to occur in an individual transmission in an unvaccinated population as it is in a vaccinated population. The difference is that less transmission is happening in the vaccinated population, so less mutations at an overall level. So vaccine evasive variants are more likely to occur where there is more transmission, so, um, not in the West/N hemisphere.

Vaccine escape is just a mutation that means the immune system doesn't recognise the virus any more. Those mutations occur randomly the whole time. When noone is vaccinated, a vaccine escape mutation confers no benefit. When everyone is vaccinated, there's hopefully not enough of a pool of cases to support lots of mutation. Somewhere in the middle there's a "sweet spot" where there's a sufficient cases to give rise to mutations and a competitive advantage to being able to access the vaccinated hosts as well.

I don't think it matters if the vaccine escape mutation confers no benefit, does it? It's still going to spread in the unvaccinated population, whether it's evading the vaccine or not. I'm just not convinced that this sweet spot exists for variant mutation that is worse than being in an unvaccinated population. This might not be what you're suggesting, but that's how it reads to me.

[AJM]

I don't think it matters if the vaccine escape mutation confers no benefit, does it? It's still going to spread in the unvaccinated population, whether it's evading the vaccine or not. I'm just not convinced that this sweet spot exists for variant mutation that is worse than being in an unvaccinated population. This might not be what you're suggesting, but that's how it reads to me.

It will still spread, and the mutation is just as likely to happen in the first place, as you say it's just chance - but in the absence of a vaccine there's no reason why that variant would become the dominant strain (unless it has other advantages too - broadly speaking extra transmissibility looks like the main advantage driving dominance at the minute). Once you introduce the pressure from the vaccine, it probably will. Which is only bad if the vaccine is your only plausible route back to normality...!

[TobyD]

Isn't by far the most likely source of variants the fact that the borders and quarantine policy is a total joke?

Irrespective of vaccination pressure etc, in reality virtually noone actually obeys a home quarantine policy, unless you have an autocratic police / military state.

[slab_happy]

25 and over this week:

https://www.theguardian.com/world/2021/jun/07/people-in-england-aged-25-and-over-to-be-invited-for-covid-jab-this-week

[spidermonkey09]

 Fucking finally! 

[slab_happy]

Also, looks like protection against hospitalization in fully-vaccinated people remains super strong, fingers crossed:

https://twitter.com/DevanSinha/status/1401946051091836936

And as a side note, it looks like Delta may be crushing Beta (B.1.351) and Gamma (P1) out of existence in the UK:

https://twitter.com/fact_covid/status/1401873652912734214

This is interesting because both of them seem to have more vaccine evasion than Delta does (especially Beta with AstraZeneca), but it looks like Delta's increased transmissibility trumps that right now.

[slab_happy]

Apparently 493,000 appointments got booked by noon today, so well done to the Youth there, good stuff.

[TobyD]

 Re local lockdown and pandemic competence, from Stephen Bushs' morning email:

The underlying problem is that while the vaccine provides a high level of protection against the Delta variant, and while younger people are less at risk from Covid-19, we still don't know if, with our present level of vaccination, NHS capacity would withstand an uncontrolled outbreak. So it is touch-and-go whether England will be able to unlock on 21 June. 

But there are some things we can say definitively. The first is that we’re here because the British government has never had an effective strategy for central quarantine and isolation, whether at the border or in the United Kingdom. (A fun, but depressing game if you want to illustrate that is to look at any Covid hotspot and work out how much we have paid hotels to furlough staff rather than turning them over the to job of running central quarantine.)

I’ve written before that one advantage Boris Johnson has is that people simply do not want to revisit the past year and are therefore inclined to give the government the benefit of the doubt. I think that’s still true. But the flip side of that is that I think most people also want the government to keep its end of the bargain up and to ensure that we do not have to revisit the past year. Failure could well have a political cost as well as a social and economic one. 

[Will Hunt]

The underlying problem is that while the vaccine provides a high level of protection against the Delta variant, and while younger people are less at risk from Covid-19, we still don't know if, with our present level of vaccination, NHS capacity would withstand an uncontrolled outbreak. So it is touch-and-go whether England will be able to unlock on 21 June. 

I don't understand this. The vaccine provides a high level of protection, and we have lots and lots of people vaccinated, so how would an outbreak be uncontrolled? The vaccine is the control is it not? Are we not aiming for low hospitalisation numbers as opposed to low numbers of cases?

Personally I'm satisfied with what the government have done thus far with regards full re-opening. They've set a provisional date of 21st June, made it clear from the outset that that date might be pushed back, they started to sound-off about it being delayed at least a fortnight ago pending more info, it's now as good as certain with final confirmation coming on the 14th. Given the complexities and uncertainty in modelling the outcome of two opposing forces (vaccine rollout and virus spread) I don't think that this is an unreasonable approach.

[spidermonkey09]

Its because of how transmissible the Delta variant is; if a large number of young people (still unvaccinated) get covid as a result, and a small % of these end up hospitalised , then a small % of a big number is still a big number. Thats the theory anyway.

Its interesting that Delta is yet to properly kick off elsewhere in the world yet (edit: apart from in India, obviously). Suggests there is something unique about the current hotspot areas that are uniquely susceptible to outbreaks; multi generational housing, lower vaccine uptake etc?

Not sure I totally agree with Bush's second paragraph. I agree it hasn't helped not having an effective quarantine system, but the variant would have got in anyway as we have gone over in this thread before.

[TobyD]

. I agree it hasn't helped not having an effective quarantine system, but the variant would have got in anyway as we have gone over in this thread before.

It might have got in but the crucial thing about having a working quarantine system is that you can delay and slow its spread. It effectively gives you more time to decide whether you want to try to contain it or to just slow it down as much as possible. If like Australia whenever you get a few new cases you lock down the area hard then you'll perhaps get closer to the former but annoy people in the area more.
I acknowledge it's far more difficult to do containment here as we're more densely populated, more airports etc etc

[mrjonathanr]

Why have isolation at all? I can’t see any functional difference between isolating and quarantine apart from the passport. It seems if one serves a useful purpose, then so must the other.

[spidermonkey09]

I acknowledge it's far more difficult to do containment here as we're more densely populated, more airports etc etc

I would say practically impossible given our reliance on imports for essentially everything. Australia also followed the hugely morally suspect policy of banning their own citizens from returning from India which I'd have been very uncomfortable with the UK doing. I accept it would have slowed it, but there would have been a significant cost.

[tomtom]

..

[TobyD]

Why have isolation at all? I can’t see any functional difference between isolating and quarantine apart from the passport. It seems if one serves a useful purpose, then so must the other.

This depends on what you mean. Enforced hotel quarantine, effective at least to an extent. Home quarantine is a myth, it would be incredibly difficult to achieve properly for the vast majority of people, I really don't believe it's practiced properly by most people.

[TobyD]

I acknowledge it's far more difficult to do containment here as we're more densely populated, more airports etc etc

I would say practically impossible given our reliance on imports for essentially everything. Australia also followed the hugely morally suspect policy of banning their own citizens from returning from India which I'd have been very uncomfortable with the UK doing. I accept it would have slowed it, but there would have been a significant cost.

Yup that's fair, that's more or less what I meant.

[slab_happy]

I don't understand this. The vaccine provides a high level of protection, and we have lots and lots of people vaccinated, so how would an outbreak be uncontrolled?

Because there are still lots and lots of people who are unvaccinated or half-vaccinated. Case rates are rocketing up in people in their teens and twenties, and to a lesser degree in the half-vaccinated age groups (and Delta takes a nasty chunk out of the protection you get from a single dose, knocking it down to about 33% against infection).

And Delta looks like it might be more than twice as likely to hospitalize people as Kent/Alpha was.

Even with that: those younger age groups still have a much lower risk of getting severely ill than others, but, as people keep pointing out: a small percentage of a very very big number can still be a big number.

People in their teens and twenties also seem to be the most effective spreaders as they go out and interact most (a 70-year-old might be much more vulnerable if they get infected, but they're also less likely to be going out partying). So it can rip through those age groups.

Hat metaphor explanation: https://twitter.com/JamesWard73/status/1402904768113254402

And the over-50s still aren't fully vaccinated yet; the government is aspiring to have offered second doses by the 21st, but remember it takes a couple of weeks post-shot for the immunity to build up.

(There's also a fair amount of uncertainty at the moment about whether 2 doses of AZ performs significantly worse against Delta than 2 doses of Pfizer does.)

Hospital admissions are still low, but they're now going up exponentially. Hopefully deaths won't follow as much (because people being hospitalized are largely younger and healthier than in previous waves), but it could still be unpleasant.

And deaths aside, the NHS is just beginning to try to tackle the horrible backlog of non-Covid treatments. You don't have to be looking at the NHS being potentially overwhelmed for it to be quite bad if a lot of people get told that their vital cancer treatments (and hip surgeries and whatever) which just got re-scheduled now have to be cancelled and postponed again.

Basically: vaccines work great, in people who've had the vaccines. Unfortunately, a significant chunk of the population is still out in the cold, or only has one foot in over the threshold.

That's going to change very fast as the vaccine rollout continues, and we're in a vastly different position from where we'd be if the vaccine rollout wasn't already at this stage. A lot of people seem hopeful that this might be manageable, if maybe a bit bumpy, given sensible decisions like delaying the June 21 re-opening for a few weeks (and doing proper surge vaccination in hotspots -- let them vaccinate anyone they can, ffs).

Personally I'm satisfied with what the government have done thus far with regards full re-opening. They've set a provisional date of 21st June, made it clear from the outset that that date might be pushed back, they started to sound-off about it being delayed at least a fortnight ago pending more info, it's now as good as certain with final confirmation coming on the 14th.

From the modelling various people are doing, delaying 2-4 weeks at this point could probably make a significant difference.

Unfortunately, looks like Johnson may still be in "let the bodies pile high in their thousands" mode:

https://twitter.com/SebastianEPayne/status/1400136894953005056

This was prior to the most recent PHE reports, but I don't have great faith in his capacity to learn.

And all the briefing about how Rishi Sunak is willing to accept a 4-week delay suggests to me that the cabinet is still fighting over it. I'm really worried that it's not "as good as certain".

made it clear from the outset that that date might be pushed back

Not to a lot of the great British public, they haven't.

[Offwidth]

Something to add is the NHS is pretty much still at capacity right now and it's workforce very tired. I can't see hospitalisations getting anywhere near previous peaks (as I think even one jab gives very good average protection against hospitalisation) but any big rise would be very bad news. It's dumb to 'shake the dice' when a few more weeks make the vaccination situation so much better and the information on hospitalisation levels a lot clearer. Lets see.... at least Boris won't be needlessly killing tems of thousands this time by making the wrong decision again, like he did in September and December last year.

[Paul B]

It's dumb to 'shake the dice' when a few more weeks make the vaccination situation so much better and the information on hospitalisation levels a lot clearer. Lets see.... at least Boris won't be needlessly killing tems of thousands this time by making the wrong decision again, like he did in September and December last year.

Am I right in thinking that 'just a couple of weeks' mightn't be the case? Previously vaccinations were accelerated due to other vaccinations becoming available, but with Pfizer being the choice below a certain age then the no. of vaccinations per day is more limited by supply? That's not me advocating against delays btw.

[Will Hunt]

That all makes sense, Slab. I'm not arguing that we shouldn't put the date back if that's what's necessary.

I'd be amazed if the date wasn't pushed back. All the "move heaven and earth" stuff is just politics. They know that there'll be a heap of people who are disappointed - particularly the fully vaccinated oldies and business owners who form a large portion of the Conservative's voters and membership - so they need to make a show of having exhausted all the alternatives. The reason that they don't drop the decision to push the date back like a bombshell is exactly the same reason that I don't suddenly say to my kids "it's bedtime" - I say "we'll have three more books then bed...two more books then bed...last book then bed".
This is, of course, just my hunch.

made it clear from the outset that that date might be pushed back

Not to a lot of the great British public, they haven't.

Is that true? I don't remember the government ever briefing that the 21st June would definitely be honoured. In fact I distinctly remember the rhetoric that was used when they produced the "road map" was that each step would be "irreversible", but that they would only proceed to the next stage if they deemed it right to do so. As soon as the variants appeared the tone became more cautious.

[slab_happy]

Am I right in thinking that 'just a couple of weeks' mightn't be the case? Previously vaccinations were accelerated due to other vaccinations becoming available, but with Pfizer being the choice below a certain age then the no. of vaccinations per day is more limited by supply? That's not me advocating against delays btw.

Hard to gauge what the limits are because there's no public info on what vaccines England actually has in stock -- they were denying for ages that there was any stockpile, then Hancock admitted it in his testimony today.

Paul Mainwood is your man for attempting to work out what the situation is with that, if you want to dive into that rabbit hole:

https://twitter.com/PaulMainwood/with_replies

However, remember that a lot of half-vaccinated people got AZ, so the Pfizer/Moderna supply isn't the limiting factor there.

Just in terms of already-scheduled second doses (and the fortnight or so it takes for them to kick in), I have the impression that a few weeks gets us a lot -- remember the difference in protection between half- and fully-vaccinated is much bigger with Delta.

They could also be a lot smarter within a fixed supply if they were willing to properly surge-vaccinate in the Delta hotspots, even if that meant temporarily slowing vaccination in area with very low rates. Right now, it's a hell of a lot riskier to be a 20-year-old in Blackburn than a 35-year-old in Devon. But they're distributing vaccine doses strictly on a population basis and insisting that local authorities stick to the national age limits.