UKC

Post 1 - Four Nations Plots

Record low interest in last weeks thread; another sign of how much Covid is moving out of people's habitual thoughts and concerns.  High hopes for wrapping this up with #52 if the data keeps catching up with the optimistic mood out there...

Link to previous thread - https://www.ukclimbing.com/forums/off_belay/friday_night_covid_plotting_45-...

There's no sign of runaway exponential growth in cases in any of the four nations despite the very mild restrictions and the return of schools  - how far things have changed from last year indeed. 

All four notions are now showing decay although for Wales and England it will need another week of data to be convincing.  Scotland in particularly is heading for some stand-out halving times (in a good way). 

Much more importantly, hospital occupancy has been reducing in all four nations (some plots on this towards the end of the previous thread), although for reasons I haven’t looked in to Scotland’s hospitals are emptying the most slowly despite their fastest decay in cases. Partly explained by factors relating to schools masking a fall in cases in adults in England, but perhaps there's more to it as well.  There've been a few notable changes in hospital metrics in relation to delta and vaccination but I've not really dug in to them or what they mean; others have on the Twittersphere etc.

Post 2 - England Ⅰ

Cases have turned to decay again over the last couple of days of data.  The next post will look at the demographics of this rise; most of it was in children but there’s been enough growth in adults that we’re now seeing hospitalisations turn to rise, I’d hoped that wouldn’t happen and I’ve fallen back to hoping the rise in admissions won’t be very rapid or very sustained; this seems reasonable given the cases data now locked in.  

Hospital occupancy had dropped by about 2000 people whilst cases in adult ages were falling; that decay has stalled for now but hopefully resumes soon.  It’s clearly needed as the effects of the almost endless pressure from Covid on hospitals mount up in the news and in the anecdata.

Deaths are falling faster than hospitalisations have done recently - this can be seen in the halving times for deaths being shorter on the far right in plot 9e, all be it in the provisional leading edge which could change asm more data comes in.  I don’t think this fall is simply explained by the changing demographics of cases to younger ages, and I’m wondering if it’s a sign of us really, genuinely reaching the end of the pandemic phase, in that we’re running out of people catching Covid without having any prior immunity - with the consequence that more hospitalisations are “minor” rather than “major”.  I return to this with a change in plot 22 in a future post.  The next ONS antibody survey is due out any day now, it will be interesting to see how that looks although it’s the one due a fortnight later that’s more relevant to understanding where we are now.  Really it's a bit too early to start drawing conclusions about the relative decay rates let alone about the underlining reasons, another week of data will be useful, but it feels like we’ve perhaps hit a major milestone.  Again, more in the next post.

Post 3 - England Ⅱ

The top level week-on-week method rate constant plots shows that cases have gone back in to decay after their latest round of growth.  The demographic version of this stops a few days earlier and shows cases in both younger and older ages heading for decay, so hopefully we have across the board decay once the reporting lag resolves, and not just the decay in school aged children masking a rise in older adults, so the return to growth in hospitalisations should just be a blip…

The big question is why are cases now falling in school aged children?  The previous random sampling results on antibodies in this range and the most recent ONS infection survey seem to fall a bit short of the numbers needed to quench growth through increased immunity.  Perhaps the sheer quantity of disruption to schools from all this is limiting things, if so it could be that we have a couple of smaller bumps of positive growth ahead, or it could be that this recent spread plus the vaccination is proving enough.  Would’t want to place a bet either way.

The likely direction of spread of infections between different ages is far more prominent than usual in D1.c; I think this is because adult ages are no longer capable of sustaining growth under then current conditions - growth which would otherwise overpower the demographic cross-links.  I say “then current conditions” as this data ends close to a week in the past, and the weather just went to crap which could change things....  So, the growth we see in older bands reflects cases driven from those in younger bands.   I’ve made an annotated version of the plot; the growth in cases in children (region 1) appears to be driving weaker growth in adult household members aged ~30-55 (region 2), and that in turn may perhaps be forcing weaker growth in older adults (region 3).  There’s a clear band of decay remaining in adults mostly too young to have children in school, and if I squint and I can almost convince myself I see another lower growth band between parents and grandparents.

If this noddy model of forwards links is right, as the cases in the young turn to decay, those in older age bands will also do so with similar lag to their “switch on” as there isn’t the “pandemic potential” in those bands to sustain case growth without forcing through household links to the young.  So, that’s what I’m looking for in the data now; if that doesn’t happen something is wrong with my noddy model meaning that the situation is more gloomy than I think.  That's often why I describe these noddy models, not because they're guaranteed to be right but because we can test developments against them to see if they're totally wrong.  This is all assuming we’d got to the point we couldn’t sustain R>1 in adults, and it’s only returning children to school that has allowed sustained growth in their demographic, driving adults.  Now  we’ve had some more immunity distributed across adult ages which should put them even further out of reach of R>1, but the weather has also gone in to a cold/wet/windy phase which is going to drive a lot more people indoors and close a lot more windows.  Bit of an open question about what happens next then…...

The other notable thing on this plot is no sign of growth in ages 15-19 over the last week; this is where we’d be expecting undergraduate cases to start landing most strongly.  It could be that decay in ages 15-17 is masking a rise in ages 18-19, but there’s no sign of rise in 20-24 either.  If we make it another week without a big university spike that’s very promising.  There’s certainly a few MSOAs I should go and look at in a week or so…. But between vaccination and the bonkers outbreaks of previous years and then during the football season, perhaps the risk there is retired.

The school cases present a much clearer/worse driver of cases in older adults than previous bursts of rapid growth e.g. in undergraduates.  Not surprising given the household links and the anecdotes stacking up over household spread since the alpha/Kent variant came along.  A piece of corroborating evidence for the transmission of Covid between children and parents (as I talked though last week, we’ve seen the apparent direction of this flip since schools returned) - see the section “People in big households more likely to test positive for COVID-19” in [1]

[1] https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/con...

Post 4 - England Ⅲ

Plot 18 shows that most regions have hospitalisations rising as the downstream consequences of the return to schools land.

Deaths in London are bucking the trend and are rising despite neither cases nor admissions data standing out there.  Looking at the raw data this could just be the noise in relatively small numbers [2].

Back from a break is plot P1.C which shows the relative distribution of cases across the ages.   With the chosen colour map you can see the bifurcation as the peak of young adult cases is replaced with two peaks in children and parental ages.   The next plot shows two sections through this four weeks apart.  I’ve added colouring to show where the relative fraction of cases has risen in that time (red) and fallen (blue).  I’m on the fence about if I like this addition or not, comments welcome.

Plot 22 is updated to just show this wave.  In past waves, the lag from hospital admission to ITU admission has meant that when a wave goes in to decay, instead of tracing a single diagonal line “there and back again”, it opens out in to a loop; reminiscent of classic signals analysis stuff with an oscilloscope in an undergraduate lab.   There's no sign of that here with a near-perfect, reversible diagonal forming.  This suggests that the lag to ITU admission (where it happens) is much reduced.  This fits with earlier anecdotal reports from others that hospitalisations are bifurcating in to the more trivial (never goes to ITU) and the more serious (goes more rapidly to ITU); if we are reaching an end to the phase where people without antibodies are catching Covid and going to hospital, perhaps we’ll see changes to the ratio between occupancy types.  It’s all rather opaque without the data broken down by vaccination status however.  

The last plot is my basic mortality analysis.

• This goes a bit further than most of my plots in that it doesn’t just trivially convert the data to other forms and plot it, but it does some actual analysis that should really be done by someone with a lot more time, area specific training and experience and preferably more longitudinal access to health records; so take with a big pinch of salt. 
• It asks how many of the people testing positive from Covid would die from pre-Covid all cause mortality without seasonality (red line, left side), and compares this with the number dying from Covid (black line, left side).    This is done using demographic all cause mortality data from the ONS for 2019, so it accounts for age effects. 
  • This ratio (right side plot) started out at about 100x the mortality from Covid vs from pre-covid all cause mortality. 
  • The increased lethality of Alpha and then likely Delta will have been raising this ratio, but improved therapeutics and clinical care have been lowering it at about the same rate. (*). 
  • Mostly vaccination has brought it down to the point were catching Covid is "only" associated with a ~12x increased risk of mortality (orange shaded band, left side).
  • Over the last couple of weeks, actual deaths have started to lower quite rapidly but the “no Covid mortality” ones haven’t - so that ratio is dropping, and showing signs of wanting to drop some more.  Some of this may well be due to the new MAB therapeutic that started going in to arms a couple of weeks ago, but it also feels like the sort of shift I’d expect to see as we run out of people with no immunity to catch Covid and then to go on to die.  The MAB therapy may reduce the ratio by 20% at most going off the phase 3 trials and we've already seen a bigger drop than that.

This analysis is by no means robust or controlled enough to be considered as proper science.  It’s the kind of analysis I really want to see done by an appropriate group however; from the data, Covid is clearly still an exceptional problem for society.  However, the hope is that this won’t be the case for much longer.  Bu, we need to understand with good scientific methodology (a) when the risk from Covid stops getting less bad and (b) how minor or serious Covid is at that point compared to other mortality risks.  I got thinking about this more from girlymonkey’s comments elsewhere in the last week on the quality of life impacts of Covid mitigations on those she cares for; the difficulty in drawing a line under Covid in an evidence based way is that we’ve instrumented and measured it in this pandemic to a high degree (for obvious, important and beneficial reasons) but this means that there’s an imbalance of evidence in favour of Covid which I think makes it very difficult to reach an objective view on when (optimistically) it is no longer a stand-out cause of mortality or on when (pessimistically) it's potency as an additional cause of mortality has been reduced as much as possible.  To me, framing and attempting to answer these questions feels like a much better use of time by academics with good access to less public, more longitudinal health data and with a lot of experience in the fields than the modelling work. 

Note I’ve been very careful to say “associated with” and not “causing” when it comes to Covid and deaths.  Mustn’t jump to assumptions here, as likely as they are.  Clearly Covid is causing most of the deaths, but if we reach a best-possible endgame, it could become one of the causes of death that only affects people very close to the end of their lives anyway.  It could add to mortality or it could displace other causes of mortality (as it displaced flu last year), and any understanding of where we end up is gong to need a careful, nuanced and balanced analysis. I'm cautious of giving my thoughts here, because whilst they apply to and anticipate a "best possible" endgame, it's also something that we've seen raised repeatedly by the opposition in an attempt to present Covid as a non-issue over the last year.  There's some irony that what we need and what I want is for all the bullshit statements of the last year to become true; and I've no doubt some will present themselves as prescient for having made them a year ago, but as with many things in life (such as my failed attempts at becoming a comedian), timing is everything.

(*) Just imaging if Delta had landed back in early 2020; perhaps 2.5 day doubling times in a pre-Covid society, symptom free spread, an IFR nudging perhaps 2.5% with hospitals intact and 4% with healthcare overload (no therapeutic improvements) and a herd immunity threshold close to 100%.  My first thought is that would have been catastrophic given our response with order of 1.5 million deaths by June 202  , but perhaps it would have been obviously serious enough that it would have been taken much, much more seriously than Covid was in many places for the first few months and we'd have had a net better outcome.  One for Marvell’s “What If?”…. Big picture:  Disaster preparedness and biosecurity could and should be done better.

[1] https://coronavirus.data.gov.uk/details/deaths?areaType=region&areaName...

Post 5 - Scotland Ⅰ

I spent so long gathering my thoughts over England this week I've rather run out of steam for Scotland.

Cases continue to plummet; just as well really given the pressures the ambulance services are under and the hospital occupancy.  Such different responses from the last dropping of restrictions either side of the border - Scotland retained much more "pandemic potential" in the young adults, having previously had much less spread in the same age than England due to their bombing out of the football much sooner.  This paints a pretty compelling picture of infection acquired immunity "filling in the gaps" in vaccine granted immunity.  A de-facto policy used repeatedly by leadership on both sides of the border that hardly seems the most cautious (!), but at long last the various politicians appear to be playing chicken with the virus and not loosing spectacularly.  I don't think any of them will be judged kindly on what it has cost us to get to this point; over and above the deaths and reduced healthspans of the survivors I particularly resent what it's done to further a certain set of views in society.

Post 6 - Scotland Ⅱ

The demographic data for Scottish cases.  

I thought it interesting that the decay is strongest in ages 20-24 (deepest blue/purple in D1.c, right side) and has been for quite some time.  This again reinforces my general sense of infection acquired immunity making a big difference, given that the strongest rises were in this band earlier on.  This doesn't mean vaccine granted immunity is unimportant but rather the opposite - it's the gaps where people haven't taken (or, for children, been offered) the vaccine that we see the most "pandemic potential" meaning ability to have exponential growth, and we're finally at the point that seems to be self-limiting.

The detail plot shows the last couple of months of demographic rate constants as line plots.  They're heading uncomfortably for growth; no great trend with respect to age other than that the younger bands are the furthest from growth which doesn't contract the idea of recently acquired immunity in the most susceptible to spreading the virus.  My best guess about what we're seeing here is that it's seasonality creeping in, cases may start to turn to growth within a week in the older people - whilst this won't immediately send the top level case figures in to growth it may do so for hospitalisations.  That's not good for Scotland as their hospitals are pretty full and aren't emptying much despite the decay in cases.  Might be prudent to think about a little firebreak, although the booster program is also going to help things out I expect.

I shared this link on another thread, have you spotted this?

If successful, it should make a huge difference to hospital admissions and deaths. 

https://www.bbc.co.uk/news/health-58764440

I commented on it at the end of the last thread.  Sounds promising but there’s some distance between their top level press release and an MHRA conditional marketing authorisation, and I don’t want to jump to conclusions re: for whom  it’s going to be recommended for use once/if it has an authorisation.  This compound pre-dates Covid as a candidate anti viral; lots to read about.  Despite that I obviously hope it is as effective as they claim, and that the reprotox concerns have been retired.

I have no idea if it’s going to work in tandem with the MAB therapy now being used in England, or if there’s a lot of overlap in who they help.  If it works as the trial suggests it makes a material difference either way.

My impression was that use of MAB would probably be heavily driven by the cost, which was very high. It seemed to me as a layman to be a difficult one to pick a strategy for - extremely expensive, but needing to be taken early before you know for sure who needs it.  If molnuperavir is significantly cheaper then it could see a lot of use. However there were only 400 people in the trial which doesn't seem like much data to approve a drug on...

Something that I find makes the England data hard to 'read' at the moment is that the bias of cases by specimen date towards a Monday seems inconsistent week-on-week. I'm not sure why that is. I think it must affect your week on week method a bit?

Pleasing to see on the dashboard that cases by reported date have seemingly turned a corner and started trending down.

Different subject; I don't understand the change in behaviour on the Lissajous plot for hospital occupancy vs people on ventilation. Why would the lag have reduced so dramatically? It's also weird that it appeared to be looping over 'normally' at the end of July things started rising again (but now isn't). This might be an academic debate with no importance but I'm wondering if there's any useful insight in there...

The MAB one was very expensive, but at the stage it’s going to be used, being in ITU is also very expensive so I think it’ll see good use but as you say not an obvious one; starting with broad use and gaining clinical experience to tighten the decision might be sensible; well out of my area/expertise.

On the small end for a phase 3 trial but not that small; reactively testing efficacy in a targeted way against a disease needs fewer participants than a vaccine trial where most participants won’t be exposed to the disease.  It’s the phase 1 trials that I’m wondering about, expert feeling appears to be that this compound needs inter generational reproductive toxicity testing and that’s a risk that can’t rapidly or ethically be retired with humans.  Picking up from offwidth’s closing comment on the last thread; despite the concerns raised  by experts here I doubt we’ll see anything like the fear mongering over this compound that vaccines saw.  Sounds like they were going away to do homework on this risk and that will presumably be part of their regulatory submissions.

I have a noise analysis of variation in the week-on-week method results; I haven’t shared it as others don’t seem to share my interest in noise analyses; it shows Tuesday to be the best day for comparing; Monday is perhaps the worst.  The key way of accommodating this is not to take a single data point in isolation but to look at the general local shape.  So, a lot more caution interpreting the leading edge if the last point is an outlier. I switched to preparing these threads on a Saturday way back when because that sees the demographic data end on a Tuesday and I had a sense that gave better consistency.  It’s one reason a weekly check in is better - if less immediate - than daily updates I think.

It tells me Something Has Changed.  For the better, I think - and as you say the blip in July looked like it still had a phase lag then, so it’s a recent change.  There’s a few really interesting things in the hospitals data I hope to see studied down the line.

I think the trial was so small because it was curtailed when they thought it was unethical to continue giving the placebo rather than a drug that appeared to work. I think 8 people in the placebo cohort died and none who got the drug.

It was stopped about half way through. 

https://www.clinicaltrialsarena.com/news/merck-ridgeback-molnupiravir-trial...

Trestment efficacy testing needs lower numbers than vaccine efficacy testing.

Thanks as always. Felt like most of the discussion last week took place on a couple of other threads rather than disappearing… 

Warm thanks from me as ever. I still read this thread most days and look forward to it on Saturdays.

Another day of data on the week-on-week method rate constant plots.  Under 15s in the more-reporting-lagged demographic data are on the cusp of turning to decay, with the adult rate constant lagging that as we'd expect if those are cases downstream of the school associated cases.  Top level cases continue to move more in to decay, good.

Also shown is the noise analysis I mentioned in my reply to Si dH. 

• The LMH plot shows the PCR rate constant signal (top) filtered in to three frequency bands (L - low, M - medium and H - high).  
  • M is a passband picked to give the most statistically significant anti-correlation to the central England temperature; squint and you'll see that the last couple of weeks aren't following the usual pattern; the school effects are occurring pretty rapidly and so fall in this pass band - but they can't keep that up for long!
  • L is baseline trend; I think it's mainly positive now because of the "false" signal from the switch-on of school associated testing.  
  • H is the part of the signal changing faster than the weather band.- mostly measurement noise.
• The next plot shows the contribution to rate constant falling in the highest frequency band - faster than most weather effects and faster than policy, variants and so on.  Mondays are often the outliers on this plot which fits with Si dH's observation.
• The final plot shows the distribution of the absolute values in this mostly noise band.  Tuesday and Wednesday are the tightest days of data for week-to-week consistency.
  • The threads are times so that the demographic data ends on a Tuesday; nice to find that that historic hunch/decision has some rational basis...

In general, analysing the details of the noise in measurement systems is something I think many people overlook to their peril...  It's amazing how much better many systems can be made by taking the time to understand the noise characteristics.  Although I haven't looked for a while, it's always bothered me that the magnitude of the noise in the cases signal is more than 10x what would be expected for a poissonian process, where-as the noise on the other signals is much closer to poissonian.  

Thanks. I think it’s important to zoom out a bit when looking at the numbers. Official cases have essentially been pogoing around in the 25-40k range since the start of August. The demographics have changed and it remains to be seen whether the growth in secondary school ages will translate into significant growth among their parents. We also have the return of uni students. I would give it a couple more weeks to see what impact all of this has, if any. I recall that at the start of September we were wondering why the return to school wasn’t having much of an impact on case numbers - until it did. These things take a while to filter through, especially with the vaccine shield.

It’s great that hospitalisations and occupancy have reduced. It looks like hospitalisations have plateaued again and presumably occupancy will do as well. If these indicators remain more or less at current levels, hopefully the NHS will manage to get through winter without coming close to breaking point. My expectation is that the Covid numbers will get worse over the winter but hopefully hospitalisations won’t be anywhere as bad as last December / January. Still, with other season viruses, it will be grim for the NHS. Rising energy prices will also be a contributing factor due to poorer pensioners having to save money on heating and hence being more likely to develop pneumonia and so on.

I’m still WFH full time and can’t see that changing any time soon…

We are also flying by the seat of our pants as regards variants. Hardly any control measures left on people coming into the UK and too many cases to be able to sequence them all.

On the plus side, encouraging news about recent drug developments. How available these drugs will be once authorised is another question. 

The question is how soon it will burn through, at least in terms of hospitalisations and deaths. Hopefully by next spring? As you say, we might be getting there already but it’s too early to draw conclusions. Much depends on the level of breakthrough infections / hospitalisations / deaths and we don’t know that yet. There have been some studies but fundamentally it’s too early to tell. 

Incidentally, at a very basic level the dashboard map appears to support the idea of approaching herd immunity in some places - we now have rural areas having higher case rates than urban areas in large parts of the country. 

indieSAGE links...YouTube

youtube.com/watch?v=qZffPwtD25c&

...and the slides..

https://www.independentsage.org/wp-content/uploads/2021/10/WeeklySlides_1Oc...

Interesting bits this week include the following:

Positivity rates not reliable right now due to a big national cold outbreak with risk of  people not testing who should (may also be reducing case rates by inference).

Government haven't published school absentee rates since September 16th

Big spike in Kettering....6% of main secondary age band tested positive in the last week.

JCVI given a ticking off as their charter promises on openness and transparency haven't been met on recent data.

Ventilation expert as a special guest after the data presentation.

greatly appreciated as always Wintertree. 

I'm very curios as to how the growth in school age children could be turning to decay already as with very little vaccine based immunity it seems odd that a threshold would be reached so soon does anyone have any thoughts on this?

Lots of good thoughts.  Optimism tempered with pessimism, or pessimism seasoned with optimism?  IIRC you hail from the former soviet block... 

They have, but hospitalisations have been falling a lot, so clearly there's a growing disconnect between the two - partly the demographics as we've both noted, partly I think also the switch-on of more testing at the start of school term masking some of the real fall in infections. 

Disagree.

I think that's almost settled entirely already from the demographic rate constant plots and where they have to now go to deliver the less lagged top level rate constant plots  Top level cases have turned to decay, school aged cases have turned to decay, and there's a period of rising cases lagging in the parents, now also turning to decay.  This should be fully settled with a couple more days of data.

In terms of rising spread of infection, it's over.  We're already seeing it pan out as hospitalisations, the extend of which will soon be determined.

The big question for me is what happens next - I think I perhaps understand why the schools seemed so slow to get started (see below) but there's no single stand-out obvious reason why it just stopped; if it is raising immunity, that's great and we're done.  If it's a response to control measures kicking in, we'll see another round (or more) of this.   For which we need...

Our rallying cry.  Problem is, in two weeks the questions have moved on...

It's always easier to understand after the event isn't it...  The rise was there from the start in the demographic rate constants, but as well as the obvious masking effect in top level data of cases falling in adults, there was I think another one which was the reversal of the direction of household infections, as adults stoped being able to sustain R>1 about when schools started, there's a period where household bourn, adult induced infections in children were falling and school ones were rising.  

These plateaus are almost certainly short term, driving by the temporary rise in adults following the schools blip.  We'll just have to wait and see if that's it for schools, or if there's more to come. I'm pretty optimistic though - adult age cases seem unable to rise exponentially regardless of how many control measures are dropped and how much they're forced (schools), and the boosters are coming up.  If we see breaking point approached, it's either going to be a bad variant or flu/pneumonia I think.

I don't think potential university cases are going to drive cases in older adults to anything like the degree seen here; both the ONS data I linked above and the reversible lag in the demographics strongly suggest to me that it's household infection forcing older adults cases here; not such an issue with undergraduates.

Yup.  The last thing we want is to be going in to winter with a lot of fragility in supply chains and energy sources; the last couple of weeks have shown how hair-trigger a lot of people are on their panic buying settings right now; bad omens.  

Only one way we're going to find out, and that's by getting there.  Spring was certainly what the Oxford vaccine people were suggesting in the article I linked a couple of weeks ago, although I fear to mention it again lest the thread get dragged down that grievance stuffed rabbit hole once more. 

I think if this isn't mostly boxed up by spring, our whole plan and direction are going to need a big rethink.  

So far completely absent from the data.  This time last year, the mega-rise had already happened and we were now in to the decay phase in the university MSOAs/ages, and the population wide rise of Alpha was starting in earnest.  No proof that it isn't going to happen, but again signs that the situation is in a much better place than last year.

Yes, I haven't found yet a source for what the prioritisation order for sequencing is.  I'd hope some mix of breakthrough and re-infection cases and importation events.  Now that we have near population wide immunity and more post-vaccination mild spread (I do wonder about these "bad colds" with their LFT negatives...), the risks from a variant fading; never to zero but less than they were.

That's the big question.  

My take above was that I'm not convinced the prior immunity levels and likely infection levels have been enough to get infection acquired immunity to the level needed to remove the possibility for exponential growth.  Same as your take basically.  This question could be resolved by future ONS antibody survey data a couple of rounds down the line.

We've often seen rapid growth to be self-limiting when outbreaks first land at the local level in the data; it could be that the response measures have been enough to end the growth; for now.  With sufficient people isolating transmission becomes difficult.  The weather may well have helped and that’s since changed.  Following on from what Offwidth posted if there is a big outbreak of certain other common cold causing viruses they can temporary block Covid infection (going off some research from last year).

Whilst this period of growth is basically over, I'm far from convinced that this is it for rises in school ages.  I wouldn't be surprised if we see the cycle repeat itself in a couple of weeks time.  I'd be happier if it doesn't...  

My guess (not based on data) is that very large proportions of school aged children have already had covid, especially during the Summer 2021 school term. Many of these kids won't have had PCR tests, either because they were asymptomatic, or had a negative LFT, or because their parents didn't want to deal with the problems/costs that a positive test brings.

Seems to be the case in general that it things will bounce through a few cycles of rising and falling so I feel like you're right on this one, I too would be happier if they didn't but its better than the whole thing just kicking off exponentially so maybe we have to be grateful for small mercies 

I thought the UK were sequencing all cases nowadays? At present the variant landscape is pretty stable - covariants.org is showing Delta dominating virtually everywhere in the world, with only one new variant appearing in the last few months in Columbia.

No, since cases rose in July our sequencing % has been disappointingly low. I think order of 20% from memory, it might be slightly better than that now. The numbers are produced when phe issue their variant technical reports. I expect another update should be out next Friday.

The UK Covid dashboard had been updating like clockwork at 4 pm for months now, the last week it's been late more than it's been on time.  I went to check PHE's Twitter feed to see if there was a note there - gone!

I missed the news from October 1st - the official switch over to the new agency has happened.

https://www.gov.uk/government/news/uk-health-security-agency-launches-with-...

The UK Health Security Agency (UKHSA), the nation’s new public health body focused on health protection and security, has today become fully operational.

"Mostly Operational" it seems.  

Wonder if any files went astray in the move?  I'm reminded of a classic exchange between James Hacker & Sir Humphrey Appleby...

Good recent update from James Ward. He expects a moderate wave in the late winter or early spring, mostly dependent on and parameterised by the assumptions used to model waning of immunity. So not over, but not looking as bad as last year.

Still not a penny I can see going into gfbl countermeasures.

I've got even less faith in the modelling than usual right now; we're facing a lot of questions for the first time over the nature of re-infections; it's not the coming wave of infection that's the key uncertainty, but the strength of hospitalisations it could cause.  The key parameters of that are not predictable by modelling, but only by the gathering of observational evidence.

Basically over by late spring seems to be the emerging consensus.  

You need to form GFBL Ltd. and start making political donations...

Another goodun if you can tolerate the obnoxiousness of the site it's on:

https://mobile.twitter.com/erlichya/status/1444747352611467265

Like many, I'll be interested to see how many "it's experimental"ists are suddenly ok with this when they get sick.

Depends how we define over...

Over in the sense that it should be settling down into whatever oscillatory pattern the endgame looks like. Not over in the sense that it could be a threat to healthcare capacity again in subsequent peaks. Depends on many unknown quantities.

Thanks for the detailed response. Lots of promising factors and if I were being optimistic (which I rarely am) I’d be cautiously betting on a sustained fall in the next month or two. However in reality I doubt that school age infections are ‘done’ yet. As you’ve pointed out, cases are in decay again, which is great, but the interaction of adult and school age infections is complex, so we might be into a bit of a rollercoaster period - though perhaps with diminishing high points. The onset of colder weather is another day factor. Another warm weekend coming up though - climate change to the rescue?

I think the impact of future ‘peaks’ (hopefully more like undulating hills) on healthcare will mostly depend on the proportion and severity of breakthrough infections. Too early to have data on that, particularly for younger age groups. Still, with the relative success of the vaccine rollout, there’s no reason we can’t have a rolling programme of booster shots for the entire population, if that’s what it takes. 

That's kinda what waning immunity means.

Rolling boosters could actually be counterproductive. The future has to be about flattening peaks more than preventing infections. Boosters deployed wrongly could worsen peaks. It's, as ever, complicated.

That's counterintuitive and not heard of it for flu boosters used for decades so I have to ask.

How/why?

Cheers!

Pfizer in the news - 90% effective against death for 6 months.

That's the sort of observational data you mentioned that I'd expect to be quickly known 1,2,3... months after start of mass vaccination.

Also phase 3 trial participants could give data for 12 months effectiveness if not jabbed since as part of mass vaccination. Tens of thousand per trial so sufficient to detect major drop in effectiveness months before it effects  people in mass vaccination programmes.

Pity it's not been on one of the dashboards. Maybe it's processed as trial and approval data and that takes time.

I'm surprised we haven't already seen panicked comments about the lack of longitudinal data on long term effects.  That seems to be a much more mainstream concern for this class of mutagenic compounds.

The other difference with the immune modulatory therapeutics I didn't see in your twitter link is that the former don't target the virus itself and so are hard for the virus to evolve around, where-as antivirals are perhaps much more subject to evasion, good reading here [1] - short story, the viral polymerase can adapt around a Trojan horse nucleoside, so anti-viral resistance is a thing. 

[1] https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.100...

Agree; quite a few people have declared "over" to be the present moment.  Bad news when the weather suddenly turns to universal suck as it has today.

Yup, don't believe a word anyone says on winter 22/23 until its history...   As discussed before, lack of such detailed instrumentation of past winter mortality seasons makes it pretty difficult to understand what "normal" would look like, perhaps.

In reply to Misha:

That's my sense, but it's not based in any sort of testable hypotheses.  I'm happy to file this under "things definitely aren't rising exponentially, confusion over details".

In reply to Elsewhere:

Sort of.  I can't imagine the control arm was maintained, and people vaccinated much earlier are going to have had different real world exposures to subsequent variants, so may have developed a different immune history to people vaccinated later, but yes it would be interesting to see what comes out of data on those cohorts now if they're still being monitored...

Good point, I should bloody well hope control arm given placebos would not be maintained!

If those vaccinated (for real) in the phase 3 trials start getting admitted to hospital it is about 3 or even 6 months in advance of when it will happen for the mass vaccinations so it's incredibly useful data. Pretty much everybody admitted has known vaccination status so it should be picked up.

Not got long to write this so will be half arsed, but essentially you can formulate a scenario when you have waning immunity, and seasonal variations in prevalence, wherein suppressing spread at certain times can, for certain conditions, worsen the peaks, even if total numbers of cases are reduced, by driving bigger wobbles on the wiggly baseline of endemic nuisance.

Flu jabs aren't given all year round. There's a reason for that.

Edit: well, a few reasons. But one of them is because it's the most effective time.

Thanks!

From Guardian live feed:

"More than 100,000 children in England are off school with confirmed cases of Covid, according to the fortnightly Department for Education figures just published.

The proportion of children at school has fallen below 90% – worse than this time a year ago – and the number off school for Covid-related reasons is up by 66% – 204,000 off in total for Covid, compared with 122,000 two weeks ago when the last stats came out.

In total 186,000 are off with suspected or confirmed Covid cases."

Apples and oranges mind you as this time the isolation requirements are less far reaching from positive testing individuals, so this is presumably a lot more Covid positive individuals isolating and far fewer others? 

I think some other places will have been watching England with great interest as this is something everywhere is going to have to go through to some degree.

The school aged cases turned to decay in today's (more lagged) demographic data to mach the top level data which continues to show growing decay in the week-on-week rate constants plot. 

The updates to plot 7 (which are less lagged than the cases and especially demographic cases plots) are encouraging - the brief growth in adult cases has slowed but not prevented the ongoing decrease of hospital occupancy, and daily admissions look to hopefully be going back in to decay; after they do the occupancy should start decreasing faster again.

I'm really not sure how useful watching us will be. We vaccinated* kids and returned them to school at almost the worst possible time and with almost the worst possible precautionary measures. Why on earth would anyone follow that? In terms of covid it hasn't helped but the real damage will likely be long term educational disparity for the most deprived and that was just as important to use precautions to mitigate against as covid spread.

* Uptakes look terrible for a western nation from overall stats (and worse for deprived areas from local anecdote) and that must be partly down to mixed messaging.

Yes but boosters can also be seasonal or indeed ongoing so that people’s immunity is continually topped up (that could be every 6m for older people, every 12m for younger ones, whatever is required basically). So I don’t buy your argument. 

Some back of the envelope numbers.  Assuming 35,000 cases/day in a population of 67 million.

Probability of catching Covid tomorrow is 0.00052...

Which means probability of not catching Covid is 0.9994....

If it stays like this, assuming the 35k positive tests is a fair measure of actual infections, and the risk was evenly distributed across the population in a 1290 day period (i.e. about 3.5 years) you have a roughly 50% chance of catching Covid at least once.  Which isn't great but isn't terrifying.

Of course the risk isn't evenly distributed, so people with high contact jobs are going to be catching it far more often than people who work from home. 

I wonder whether if Covid is allowed to become endemic at these levels it will become a occupational health issue in that the cumulative effects of multiple infections from Covid will make a long term career which requires a lot of personal contact difficult.

Circles back to what we were saying on the first few of these threads; most realistic ending is that this becomes flu 2.0

Working in HE, I and many of my colleagues would get clobbered by respiratory illness around December each year - lots of in person teaching in often poorly ventilated facilities, with the fresher intake drawn from across the nation and globe, and mixing their cooties with a few thousand others in the term 1 shenanigans and in their deeply sub-standard (yet expensive) accommodation blocks.   I took an absolute clobbering going in to the winter of 19/20 - nothing like the symptoms of Covid as it emerged a few months later, just a clobbering.

Respiratory illness is massively seasonal, and knowing what we know now it seems likely that workplace transmission is a big part of that picture, both directly in terms of individual infection and societally in terms of sustaining R>1 for months on end and ramming healthcare to dangerous levels (although, to be clear, it's effectively policy that healthcare is run without sufficient headroom for calm operations through the winter period - compare our ITU levels vs some other European neighbours for example).

If we don't understand the whole issue of respiratory health and the workplace, we're not going to be able to understand where Covid fits within that.   To be clear, I think that at the moment Covid is an absolute stand-out cause of illness, hospital occupancy and death, but I think it's going to be difficult to understand if or when it isn't, as the instrumentation of illness is so heavily tilted towards Covid at the moment (for obvious and entirely justified reasons).

The big question is whether it regularly causes long term damage as suggested by reports of organ damage and the fact of long Covid.  If the damage from Covid is long term and cumulative in the sense that it makes you more vulnerable to Covid and/or other disease in the future then the idea of letting it run at a high rate is less tenable.

I don’t think there’s any question that’s it’s had awful, enduring health effects on lots of the people who’ve caught it without prior immunity snd and survived it.

When it comes to cumulative effects however, very few people are going to repeatedly catch covid without prior immunity for a second or third time.

Yes, we have to see where covid ends up compared to all the other circulating viruses that contribute to our almost totally accepted annual winter mortality.  As I said a week or two ago, I’m particularly interested in expert opinion on where they think this is going, and what I’ve seen so far isn’t extraordinary.  But, it’s a question that needs designing and testing against so we can understand where we are.

Edit: to be clear, where we are now in terms of mortality is still stand-out bad.  But by the spring we need to understand how that’s changed and if Covid is going to remain an exceptional risk or not.

Interesting news article here, going all the way back to the first recorded Covid outbreak in Scotland https://www.bbc.co.uk/news/uk-scotland-58810370 . Claims there was no subsequent community transmission, based on genetic sequencing evidence. The claims seem to be restricted to "no subsequent community transmission" **in Scotland**, which is a pretty big disclaimer given that many delegates were from further afield. Still seems like quite an achievement for the early days of the pandemic, though, when we knew a lot less about the virus than we do now.

The big take home for me from that is the Scottish authorities suppressed information on a massive and early super-spreader event, ostentatiously under grounds of patient confidentially which it seems don't actually apply...  Given how this fell so early in the timeline it seems to me like that would have been a critical piece of information in terms of evaluating and mitigating risks, and that it could have made a material difference to how the public viewed the risks.  One person infected more than 50% of the attendees at the event.  

Being open with information in a pandemic is critical.  

Definitely agree about the suppression at the time being very dodgy and counterproductive 

The actual take home is the BBC has an agenda of undermining the Scottish Government and consistently tries to paint things in a bad light in order to further the unionist agenda of its paymasters in Westminster and Tory appointed board.

The closer you get to an Indyref the more anti-Scotland nonsense the BBC and particularly BBC Scotland come out with.   There was a study of BBC headlines after Indyref 1 and it was absolutely ridiculous how many contained the word 'warning' and 7 years later there's a large correlation between the businesspeople feeding warnings to the BBC and people who have since been put in the House of Lords by the Tories.  

They made ridiculous allegations repeatedly about this event spreading Covid in Scotland and throughout the world because they needed to have a talking point against Scotland to balance all the news coming out about the Tories.  Then when the sequencing showed their story about it being seeded from this event to be a complete fabrications and they have a low key report and instead of apologising for lying and admitting that the response from public health Scotland was exemplary they come up with a secondary allegation about 'lack of openness'.

People are definitely catching it more than once and there are definitely cases where it is more serious the second time.  Obviously it may have been a higher viral load or a different strain causing the second infection to be more serious but it could also be that if you are not as well the second time as a consequence of serious illness the first time you are more vulnerable.

The concern I have is we are still looking at death and immediate hospitalisation like they were the only consequences of Covid infection and making decisions on the balance of risk based on that when we know there are long term issues.

Yes.  I know.  What I said is that almost nobody is going to catch it more than once without any prior immunity the second time around.

Lots of good questions in there for researchers to answer I hope.  Understanding how immunity builds and how vulnerability builds in some and fades in others is important, as is understanding if the vulnerability from an infection acquired without previous immunity is “special” in terms of being more vulnerable to a covid re infection, or if it’s across the board weakness to any future infection resulting from damaged health.  For the later, controlling Covid is clearly not *the* key to protecting their health.

There are two separate issues conflated in your post I think, one is the large number of people with health worsened by pre-vaccination covid and their increased vulnerability across the board, and the other are people who remain vulnerable after infection or vaccination.  

This is the best reading I’ve found on the later - https://www.thelancet.com/action/showPdf?pii=S1473-3099%2821%2900460-6 - it comes with a cautionary note about not over interpreting some findings due to confounding factors, but it makes it clear there are characteristics common to those remaining more vulnerable after infection.

I don’t think they’ve ever been looked at as the only consequences, but it’s been very clear from the start that political decisions over lockdowns and closures were driven by the need to protect healthcare, it would be unusual if we now adopted tighter control measures over much a broader remit.  I’ve always been in favour of more control measures, but I also recognise the context in which they were approved and the wide range of different interests from a very diverse population.

What is needed I think is much better advice on identifying and protecting those who remain more vulnerable including responsibilities on employers and institutions, better enforcement of ventilation on public transport in particular and retaining mask restrictions in shops etc.

It might become like the flu in terms of its impact on health and healthcare as long as we have high enough uptake of rolling booster vaccine programmes. How high is ‘high enough’ and how regular the boosters will need to be remains to be seen. We will find out over the coming years. So I sort of agree with you but it’s not yet clear what measures (vaccination etc) will be required to reach that position. I doubt we will reach that position without some level of ongoing booster vaccines though. 

I just hope it's not a perpetual bad flu year. Even after mass vaccination it's still worse than a bad flu year. Hopefully case and deaths rates will go into sustained decline. 

Anecdotally - and I know this is the thread for anecdote over data ; ) Beeb website today has articles on both masks possibly being made mandatory in schools and re-implementation of work from home where possible guidance.  Do they know something we don't?

Latest ONS long covid (self reporting) data shows nearly 2% of the UK are affected and over 200,000 said their ability to undertake their day-to-day activities has been “limited a lot”. . Up fairly sharply from the August report, especially in the 17 to 24 age group..

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/con...

Has the preliminary data for the effectiveness of this years flu jab been released yet?

Lower population immunity from last years lockdown and limited information on strains due to limited flu worldwide resulting in lower effectiveness could mean we’re in for the mother of all flu seasons.

I'm loath to predict but my money is on the opposite....not enough flu around.... precautions are greater than normal....and a lot of the most vulnerable have already died from covid.

I was wondering that today.   

I have no sense of if going to see a train of waves through schools or if we've had all we're going to see there.  A lot of uncertainty.  

The recent data made it clear that rising cases in schools is bad for adult cases and for hospitalisations, so stretching any future peaks of school aged transmission would help with healthcare.  I don't see it doing much for individual disruption to education unless vaccination moves to two doses for 12-15 and comes in for younger ages - it just spreads it out more in time.

I've a nasty feeling that we're going to start seeing rising cases in adults across all ages (not a school linked, parent age concentrated effect) from the turn in the weather.  England remains far too close to growth potential.  Scotland has had enduring but not strong decay and that's faltering in sync with England and with the grotty weather. 

My optimism has been fading as week after week cases in England don't quite go in to clear, enduring decay.  There's always been some likely identifiable reason, and we should be running out of such reasons "yet still, they come".    

I'd hoped for a lot more decay in hospital occupancy than we've had - they're down about 22% in the last 3 weeks in England - and winter and all its uncertainties are getting closer.  It wouldn't take much change to shift things to enduring decay, and it would be good to go in to winter with healthcare less full.

What I'm completely unclear on is why rate constants aren't falling much more for cases - are we still not running out of people without immunity to catch Covid, or is it now mostly driven by re-infections and first breakthrough infections?  Ideally we'd see this break down and hospitalisation and deaths data by this breakdown.

Lots of pondering.

40k today

Also anecdotal - our local schools are now struggling with staffing levels. I'd surmise this to be a general problem as teachers have been put in a worse position this year than previously, given the quasi-covert policy to have children achieve herd immunity by infection; and if this is the looming difficulty then it would make sense that Zahawi is the source of the speculation - he'd be hearing increasing complaint routed via LAs.

Have an upvote for the thoroughly discomfiting Jeff Wayne/Wells ref. Will we be rescued despite ourselves by "our microscopic allies"?

Even more anecdotal: I've seen 4 out of our team of 18 go down with breakthrough infections in the last few weeks. All double-jabbed, as are the whole team, who were in the frontline healthcare batch of vaccinations, so that would have been January first dose and March second dose. The 4 are all mid-50s, and their circumstances of infection don't seem connected/traceable to one another. Difficult to resist jumping to a conclusion that their immunity has waned; moreover I'm surprised at what a hard time they're having of it: none has recovered fully.

It’s still bobbing around within a broad range - a bit up last couple of days by reported cases, perhaps a reflection of the weather. We might expect a slight rise, then a bit of a drop as the coming weekend is looking pleasant, then a rise again. As you say, we need data on break through and reinfection rates to work out to what extent this is the driver.

I’ve been watching a few student heavy MSOAs in Birmingham and there’s been no massive rise like last year, more of a blip really. That’s in line with what you were saying earlier. 

It all seems a bit worrying... We are happy with a high transmission / low hospitalisation rate (although hospitals are still seeing a significant amount of work due to COVID...)

We have put all our trust in vaccination, yet the COVID program has stalled a little (perhaps in part because of the hesitancy around youth). Physical measures (masks etc) have been given low priority (particularly in England). It does seem that some countries are managing to keep some measures in place without collapsing their economies).

There is high community transmission with relatively low morbidity and no new serious mutations appearing yet. YET. (Unless the relative lack of selective pressure is suppressing mutations, and Delta is the optimal mutation for the virus).

With the background of other respiratory infections, ongoing transmission, and reduced travel restrictions it will be difficult to reliably spot a new strain before it has spread (and is there the political will to act if it is identified early?). I worry that our neglect of support for physical measures will mean there will be little to impede viral respiratory infections spreading (and perhaps virulent pneumococcal infections, which may spread more easily than we care to think).

Flu as always is unpredictable, both in the illness generated and efficacy of vaccinations. There is talk of promoting flu vaccination, but if you book your COVID booster through the nhs website you don't get an option to also have flu vaccination at the same time. I think this is a significant failing. Surely NHS England could devise a booking system where you can add flu on to your COVID booster appt (certainly the centre I attended was doing flu, flu+COVID and COVID, - so it can be done - but the flu options were only available for people who had booked through their GP surgery rather than direct).

I think it is going to be a hard winter with a strained work force, and politicians retreating back to the safety of Brexit   .

Thanks for all those comments.

In terms of our ability to spot a new strain early on, something I've not found any clarity on is what the rules are for prioritising the significant but limited sequencing capacity.  Presumably some mix of younger (pre 45s?) breakthrough infections within a 9 month window of second jab and imported cases is a sensible starting point?

The counter to some of your worries is that if we do start to see other infections spreading to a worrying level, we know after last winter what works against many of them.  That doesn't mean politicians or employers will embrace it, but it opens up possibilities for higher risk individuals at least.  

One thought bubbling away in my head is the role of employers and workplaces in spreading influenza in a "normal" year. The sweeping changes (more to say on that but not here [...]) made to ventilation systems in response to Covid have potential with regards other illnesses as well that we can't pretend to be unaware of even if Covid fades away one day.  Rights, responsibilities and interpretation of laws all change with the weight of evidence now at hand.

One thing I've been mulling over to add to a hard winter; the Covid-era requirements on ventilation are going to raise the cost of heating offices, schools and other facilities significantly over winter; we were saved from this last winter in large part by lockdowns and closures in Jan/Feb, but hopefully that won't happen this year.  Have the powers that be stockpiled the significant extra oil and gas this is going to require, or is there a looming energy crisis buried under all of this?  Certainly an LA crisis without significant extra central funds to cover both the rising cost of heating fuel and the massive extra demand looming this winter.

 Integrating proper HEPA filtration and potentially UV-C sterilisation in to facilities level air handling systems offers a way to reduce the heat loss, but the CIBSE and HSE guidance is far from clear or consistent on this, or even helpful at all in the case of CIBSE IMO.  Likewise mechanical heat recovery ventilation should help, but the guidance there doesn't seem sufficient for institutions to be able to make decisions whilst showing compliance, but I'm still trying to get my head around how large organisations look at these things. 

It’s worrying to see how the government’s response to covid might be influenced by right wing pressure groups buying parliamentary influence.

https://bylinetimes.com/2021/10/07/founders-of-koch-backed-covid-disinforma...

Funny how the group behind the largely discredited Great Barrington Declaration has now morphed into a seemingly innocent charity called Collateral Global.

https://collateralglobal.org/

Partly funded by the American right wing Koch Foundation.

https://bylinetimes.com/2020/10/09/climate-science-denial-network-behind-gr...

Nothing wrong with a diversity of opinions but when disinformation is presented as being scientifically valid in order to exert political influence it can lead to the government making bad decisions as happened last September.

https://bylinetimes.com/2021/02/11/records-confirm-turning-point-boris-john...

Sequencing priorities are briefly outlined in the variant technical briefing reports. The new one came out on 1/10, at a new link due to the change from PHE to UKHSA:

https://www.gov.uk/government/publications/investigation-of-sars-cov-2-vari...

Page 7/8 of briefing 24. The sequencing strategy for pillar 1 and 2 is:

• hospitalised cases and hospital staff

• cases among international travellers

• national core priority studies

• as near random a sample as possible from each region, to the maximum coverage allowed by laboratory capacity

The number of positive cases fully sequenced is currently at about 20%, or about 30% if you include those genotyped.

Edit to add, that sequencing strategy has been unchanged since cases got high in ~ July. Prior to that a much greater% were being sequenced and the strategy was different; I think it included (e.g., off top of head) anyone with prior infection or who had been vaccinated, but not any more. Purely by numbers of cases in vaccinated people, it's clear that many breakthrough infections are not being sequenced. Disappointing really, I had hoped we would keep sequencing% high but that is going to require either a big capacity increase or a reduction in number of cases by 3-4x.

Thanks.  I tend to skim to the figures in the briefings, glad to have your detailed extraction from other parts.

Yes, it would be much easier to be accepting of the relatively relaxed attitude to case numbers and particularly the dropping of most of the red list if there was sufficient sequencing going on.  The scale at which we're doing it is still mind blowing, but so are the daily number of infections.

It seems to me like stand-out breakthrough infections can start to be recognised given the pattern emerging for what is "normal" - factors like age and time since second dose, perhaps accounting for personal risk factors.  Would seem a sensible way of making use of limited capacity.

Something else I'd love to hear more on but haven't seen discussed is how the sequences are analysed.  I can't conceive how expert humans can meaningfully scrutinise sequences at this rate, so there are presumably some automated criteria to flag them, and I'm curious about what they do there.  

This lot are a f*cking Hydra.

Often the front companies for these organisations have Company Officers recycled from companies fronting Pro-Brexit campaigns.

Who is on board here?  The Companies House page is quite different.

https://find-and-update.company-information.service.gov.uk/company/12998042...

One of the names on there is going to ring quite a few bells.  Wonder what the relevant entry on the University of Oxford's conflict of interest register says? 

The Covid related influence from this f*cking Hydra goes back to March 2020 at the least I think, and the playbook they used was well developed over climate change and tobacco.  

That's what I was wondering. If we're sequencing 20-30% any significant variant will show up before it's caused 5 or 10 cases, multiplied by some uncertain factor for asymptomatic cases. However picking it up when there is a flood of insignificant new variants means it needs to stick out (eg associated with severe illness) or observed to outgrow other variants and too late to do much.

So far it is looking good - all approved vaccines remain highly protective against serious illness for the variants we know about.

Fingers crossed the virus has explored most of the ways it can mutate to escape the vaccines - any idea if that is a realistic hope? Or just unanswerable.

I suppose it hasn't happened to flu but probably has for diseases where we've had good vaccines that continue to work for decades. 

An excellent use of language, I couldn’t have expressed it any better! 

That's the biggie isn't it.

How to answer it?

• Serial passage lab experiments - good for measuring escape against neutralising antibodies; delta is already down that path and experiments before delta made it clear the virus had that potential
• Wait and see 
• Past coronaviruses - how many times have they mutated to the point they escape naturally acquired immunity to the point of (re)gaining pandemic potential
  • This seems to have happened more with influenza than with past coronaviruses but I'm not sufficiently well read to pronounce.  Flu has more gene swapping going on than historic coronaviruses however.
  • It's also not directly relevant to single-protein vaccines especially when the selective pressures of adapting to humans likely apply to the RBD which is also the prime site for neutralising antibodies.  This is where I'd hoped Valneva would extend the "vaccine bridge" towards naturally acquired immunity.    
• Computer modelling.  I don't know how close that is to being useful.
• Expert hunches - the people who are steeped in protein structure, evolutionary changes and who have good hunches are probably too cautious to share them...  
• Other than mutation, what about (another?) recombinant spike swap, either as a donor or an acceptor?  The spike seems pretty powerful, could some other virus borrow it?

There're hundreds of viruses in circulation where immune escape could be a problem, especially perhaps if driven by a recombinant effect.  That's one way the next pandemic could start.  If Covid moves in to the viral pantheon humans carry, it's not clear to me that it's particularly unique as a threat of an escape variant.  If anything, it may have reduced the potential for a future pandemic coming from the same animal reservoirs, particular for people with broad spectrum immunity - infection acquired or a decent inactivated virus.

I can think of endless scenarios and can put probabilistic bounds on none of them, so I should probably shut up and stop making noise. 

If I was looking to borrow trouble from the future, I'd be fretting about the US Seawolf-class nuclear fast attack submarine that just dinged something in the South China Sea damaging the craft and injuring crew.  With that, the record levels of CCP airforce incursions in to the Taiwanese ADIZ  and the UK carrier strike group having just entered the area on its second "Freedom of Navigation" exercise, it's feeling a lot like the kind of situation where a genuine accident can occur and rapidly escalate.   Billy Joel really needs to update a classic -  youtube.com/watch?v=eFTLKWw542g& - in the coming climate era perhaps it can end "Rock and roll and water wars, I can't take it anymore"

Thanks for your insight (far greater than mine).

I'll stick with the "So far it is looking good - all approved vaccines remain highly protective against serious illness for the variants we know about".

Potentially deluded but happy is a nice place to be!

Mainly just listing what I don't know...

Some details of Alice (the MERs pandemic simulation) now public.

https://www.theguardian.com/politics/2021/oct/07/coronavirus-report-warned-...

Plus the latest ONS infection report is out 

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/con...

Many of the recommendations seem like they would have left us better placed for this pandemic had they been followed.

The document is surprisingly light on redaction; the framing scenario is perhaps most heavily censored.  I'm very curious to know what it was now - must have been inflammatory!  I very much want to know the content now, as utterly irrelevant as it is....

A group of ▒▒▒▒▒▒▒▒▒ travelled to ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒.  Some of the group were from London ▒▒▒▒▒▒▒▒▒▒ and the others were from the Birmingham area ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒.

Perhaps Nena.... youtube.com/watch?v=Fpu5a0Bl8eY&  or is that too close?

I think that’s what comes next.  For the present, the Levellers sum up my mood pretty well.

youtube.com/watch?v=OMIyNWav3-I&

Then again they recorded that 30 odd years ago; perhaps we live in the city forever on the edge of darkness.  (To mash a couple more pop culture references in there)

Some extrapolated case information and estimated CFRs for Spain as the pandemic progressed:

https://www.nature.com/articles/s41598-021-90051-7

Watching " The Papers" on BBC News 24,  tomorrow looks very bad for government, from two select committee assessments of the government covid response.