The Coronavirus Discussion Thread.

Not sure that's quite right DrJ. George Osborne's analysis seems more likely to me - that he has a need to be optimistic all the time and just cannot consider the probable bad outcomes.

To get out of this as quickly as he's saying we need a) the Virus to behave itself, b) people to behave themselves and the c) vaccine program to meet expectations. Say each of these is 50/50 the most probable outcome is we're in the shit longer than anyone hopes or wants.

https://www.msn.com/en-gb/news/uknews/we-hope-for-the-best-with-covid-and-as-a-result-fail-to-prepare-for-the-worst/ar-BB1cuvTx?item=flights%3Aprg-enterpriseblended-t%2C1s-ent-microsoft&ocid=entnewsntp

has he got a computer? Get him one if not. Done beers with mates via Zoom etc loads, very enjoyable, plus you can see mates who aren’t local which is much more difficult in the actual pub! Start/resume a hobby… you can get pretty much anything you want delivered next day from Amazon. Get him some Lego/Meccano/whatever. Chess.com. Online forums. Get him on here! I can understand people on furlough who are worried about their jobs not being able to enjoy their time “off” in lockdown but not a retired person!
Loads of online volunteering options too if he wants to do something that matters.
https://www.standard.co.uk/escapist/charities-remotely-volunteer-lockdown-a4400156.html

He's great on a computer and likes a Zoom, but he's spent 70+ years meeting people face-to-face, even if that's just for a chat to the newsagent, he wants to see people in person.
He also got all the hobbies he wants/needs, but again, they're not the same online as in person.
It's not about him enjoying retirement, I don't think enjoyment is the right word at all, it's that craving to be with others, to have a quick chat about the weather/whatever, the informal conversation that has been so lacking since March. You can't replicate that online, certainly not when you're not a "digital native"

A lot of us (certainly those off work for a year) understand the want to go out & do “something/anything. One half of me constantly wants to, whilst the other wants to hide under the table!

This is my view, I don't want him out and about in case he catches it, but I also know that if he doesn't go out and about there will be other troubles to come.

It’s easy to say they’re wrong for doing so, and maybe they are, but you also have to see it from their perspective as to why.

A lot of sympathy for that - my folks only interaction is if they go to the village shop for a paper, and it pretty much has been for a year. They are sensible and I don't begrudge them it, but we pop round to chat by the doorstep a couple of times a week, 2-3 phone calls a week - no interest in IT, or new hobbies, and after nigh on 60 years of marriage, not much interest in each others company either.

The elderly people I know who have tried to stick to the rules this year are looking much older as it takes it's toll.

it’s that craving to be with others, to have a quick chat about the weather/whatever, the informal conversation that has been so lacking since March. You can’t replicate that online

no interest in IT

This explanation was advanced in The Grauniad recently:

Yeah it's not my original thoughts either ... I'd originally thought that the lack of decisions until it is too late was trying to drive an agenda, now I'm starting to think perhaps that is the agenda.

Not sure that’s quite right DrJ. George Osborne’s analysis seems more likely to me – that he has a need to be optimistic all the time and just cannot consider the probable bad outcomes.

The two aren't mutually exclusive.
What leads me a bit away from that is I believe there is more or less only 1 real bad outcome from Boris's perspective and that is not being PM or important.

If it wasn't for Trump and Kim Jong-un I think people would be questioning his sanity and fitness more but they are setting a pretty low bar.

have you actually bought them a computer/tablet, stuck them in front of it & shown them how to use it?

Yes. Several.

And they use Amazon for what they need to order.

Not everyone over the age of 80 will ask "how high?" when you expect them to jump.

have you actually bought them a computer/tablet, stuck them in front of it & shown them how to use it?

Not sure if this is directed to me or anyone else, but in my Dad's case, he worked in IT for 50 years, he knows his way round a PC and does use it. But it's just not the same as meeting actual people, and he knows it. Same with phone calls, it's great, but it's not a real chat.

Hence the fella in B&Q will get a 15 minute chat about shades of paint or types of saw. And someone will come on here about the old boy in B&Q taking his time over his purchases...

I've said this before, but I'm 40, my 40th year won't be that different to my 41st, if I miss a year it's not a big thing. When you're younger or older each year is much, much more important as they're forming and learning years in the former and they're end of year in the latter. In both circumstances you want to make the most of them in a way that people in the middle of life don't need to.

Hence the fella in B&Q will get a 15 minute chat about shades of paint or types of saw. And someone will come on here about the old boy in B&Q taking his time over his purchases…

Not everyone over the age of 80 will ask “how high?” when you expect them to jump.

They’re lovely lovely people and would help anyone out….but it’s really really starting to wear me down watching their behaviour. It also really worries me….my girlfriend has never known her dad and was brought up at her grandparents with her mum. Her grandad has had a few health issues and she is terrified of losing him…..he really is basically her dad.

Tell him that she's terrified of losing him, he's probably to much of a twit to realise how much he means to her.

FDA weighs in... Ouch!

https://www.fda.gov/news-events/press-announcements/fda-statement-following-authorized-dosing-schedules-covid-19-vaccines

We have committed time and time again to make decisions based on data and science. Until vaccine manufacturers have data and science supporting a change, we continue to strongly recommend that health care providers follow the FDA-authorized dosing schedule for each COVID-19 vaccine.

Not everyone over the age of 80 will ask “how high?” when you expect them to jump.

But they're not being asked to do anything. They're being asked to do absolutely bugger all 😉

That's a nice bitch slap from across the Atlantic, the FDA are a constant source of entertainment. I've been reading some 483's for a bit of light entertainment recently, they never fail to give me a wry smile.

TiRed, do you think the reason that the Americans are more hesitant to make dosing regime changes is because they have a lower infection prevalence per capita? Are we operating out of blind panic now or at least with a different risk benefit analysis?

Furthwer on retired nurses:

As you probably know I am one and I retire soon. I have been wrestling with the thought of " am I needed / should I volunteer to stay on"

There are numerous factors around this but basically I am done. My compassion and patience is exhausted. I could volunteer to stay on / to help but I really fear for the effect it would have on my mental health. I also really fear for nurses skills that are being brought out of retirement. The reason we lose our registration after a year out of work is our skills soon fade.

I guess if the situation gets really desperate I might but I have not made a decision yet. The prospect scares me.

The FDA's motto should be "In data we trust". It is exactly the response I would have expected. Basically show me the data. I think the UK decision is a challenging balance - And I spend my days extrapolating data. But for matters of unknown duration of efficacy, population confidence and pragmatism, I'm (unusually) siding with the FDA on this one.

Vaccinations will basically reduce mortality, hospital admissions are predominantly in those who won't be vaccinated for some time yet.

I suspect the reason the fda is being like that is both a combination of being risk averse and not wanting to get sued. That being said if pfizer don't have data then we shouldn't be doing it really.
Some of the discussions I have had with the fda/barda both on products and in inspections have been interesting.

Interestingly i wonder if this is the start of the updated post brexit regulatory regime in the uk. I suspect it is more just a governmental decision of near panic.

Are we operating out of blind panic now?

id say so

mixing-up dosing regimes is a gamble, theres some logic too it , but its still a big gamble

Also have we done talkradio being booted off youtube

raises the question whether Ofcom is doing its job allowing them to broadcast nonsense unchallenged

here a great website that has some of the lockdown sceptics & disinformation pedallers worst comments (including Johnson)

https://time.graphics/line/455000

Surely the MHRA's advice will be operating on some kind of modelling TiRed, to make this risk benefit calculation? Whilst I can see your point, I can also see the value in the agility that the MHRA have shown during this crisis.

I suspect it is more just a governmental decision of near panic

Someone more knowledgeable than me will be able to explain this better, but it does sound like the first dose as as effective as 2, just maybe not as long term.
https://www.research.ox.ac.uk/Article/2020-12-30-oxford-vaccine-regulatory-faq

So on that basis, it makes sense to get through the 13m in groups 1-4, giving them a first dose as quick as possible to give them some protection, before going around again, for the second dose to give maximum protection?

Plus, it sounds like the recommended time between the 2 doses is 8-12 weeks anyway, so it'll take at least 8 weeks to get through the first dose anyway.

Just over 60,000 cases reported today. Dare I say it, cases are starting to level off a little? Just over 800 reported deaths, also deaths leveled at around 550 a day. Obviously this will climb in the coming weeks.

I'm very tired today, I really need to get away from the internet for a bit!

some kind of modelling TiRed

😀

It's based on and observation of infection balance immediately before the second dose. Data from the NEJM publication that was submitted to regulators. Choose where you think enough immunity is evident. ALL of the inference is based on the separation at 14d and likely progression thereafter. Which is really only FOUR events on the active vaccine.

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

The Oxford one maybe, haven't seen the data, but they are going against the pfizer data by extending that vaccine second dose time.

The numbers are pretty light in that chart.
The comparison to placebo is compelling though.

It's very compelling data that moves vaccine technology on. But the one dose strategy is hinging on four infections from 14-21d in the treated (red) arm. And of course for low events there is a day of the week effect on reporting. Note the infections tending to come in pairs in red but not in blue.

ONS estimate in the briefing now of 1:50 people infected

@TiRed for the pfizer vaccine were they using reported symptoms to trigger tests to confirm infection, or were they testing everyone?

So your issue is that the amount of infections the treatment arm might receive is too low?

Or is it the degree of separation between the two arms from day 14? ie not enough seperation?

I don't have time to read the full paper yet and digest it, but how does the efficacy stack up not only against the placebo but against the standard regime? Is it less efficacious or more? If it is less efficacious have they made a risk-benefit analysis considering case numbers and rate of spread?

or were they testing everyone?

Reported symptoms triggering a PCR test.

So your issue is that the amount of infections the treatment arm might receive is too low?

No, it is that extrapolation to one dose hinges on low numbers of events from day 14-21. What if they had been more spread out? One occurred a day or two earlier, or later. What if there were 3? events Or 5 events? There is very little informative data, hence precision of extrapolation will be very poor indeed.

Sorry TiRed what events are we talking about here?

Infections - they are the dots on the plot - a circle is an single patient being infected at the time on the x-axis after dosing. You will see 4 dots from 14=21 days in red. Blue placebo infections occur at a pretty constant rate, hence they fit a straight line with even spacing between dots.

Confirmed infections is my reading of it.
I do find it odd that given we know that there are high levels of asymptomatic infections that they were not doing routine pcr. Surely there is an inbuilt risk that the vaccine could simply make a lot more infections asymptomatic rather than prevent infection. Which wouldn't be picked up within the trial.

Journalists asking all the pertinent questions at this press conference on now… non-answers… why no follow up questions?

If my retired father is anything to go by, they’re bored out of their brains and completely fed up. I don’t agree with him going there, or indeed his daily stroll to the shop for a paper, but I understand why he does it.
He wants some human interaction, some purpose, something to do. he can’t see his mates for a quick pint, he can see me, my brother or his granddaughter. He spent his entire working life talking to people, interacting, and for the last year he can’t do that, and it’s beginning to show. He’s struggling.
It’s easy to say they’re wrong for doing so, and maybe they are, but you also have to see it from their perspective as to why.
I don’t expect this to be a popular view…

I think you might be surprised! I certainly understand the why he would want to do that. A lot of us (certainly those off work for a year) understand the want to go out & do “something/anything”. One half of me constantly wants to, whilst the other wants to hide under the table!

I can definitely see it from their perspective, especially as I'm not working currently, live alone and am suffering the same sense of isolation but to a lesser extent. My dad is about to go into a 14 day isolation period for a cataract operation and I've got the difficult issue of getting him to obey it. He's so used to going to get the papers in the morning with the dog, walking him again in the afternoon then going to the pub most evenings that he is lost without that routine. I've got to go to see him tomorrow to do a big shop and clean the house (carer's duties, neither him or mum can do things like make their beds easily) then try to get him to understand that he can't just pop out for a bit until the operation as a positive test before it will delay it and put him at further risk. He's determined to walk the dog every day (I'll go when no-ones about is his logic) so stopping him will be nigh on impossible, all I can do is ask him and let him live by any consequences. It's the reason I get so angry seeing the old people ignoring the rules nearly everywhere and seemingly not caring at all.

I can understand why they are like that but it doesn't make it any easier to stomach.

Ahhhh, so you consider the sample size to be too low? Essentially that the separation isn't strong enough at 14-21 days considering that only 4 patients were infected on the dose 1 arm?

With this considered (puts QA glasses on) what is the patient impact of actioning this incomplete data? I can't see any yet? They wouldn't have received the second dose in that timeframe would they? I like stats, I'm studying stats when I have time (currently on hold) - but what I really really care about is impact to patient.

Where the impact to patient comes from is leaving the second dose to 12 weeks, where we can see that red arm slowly start to rise. The impact will come from two things - that red line rising at the 40-50 day point and less potential efficacy vs the standard regime.

If it doesn't impact the patient, I care less about the data being a bit meh.

So you consider the sample size to be too low?

Yes. Precision of extrapolation from low numbers will be wide and sensitive to when those 4 patients were actually infected. Not impossible, the data is the data, but there is not a lot of data to extrapolate from. After the second dose, the data is unequivocal.

See update TiRed.

Where the impact to patient comes from is leaving the second dose to 12 weeks, where we can see that red arm slowly start to rise.

Reduced protection below that promised. I might look at some sums to show the effect.

So reduced protection before 12 weeks? That's what I care about. If that can be shown, I'll side with you.

But what I am also also suggesting is that if this is the case, I'm sure this has been factored in to the MHRA's decision to green light the 12 week regime - there may be a public health case.

Also, apologies TiRed if I come off as rude - I went into my "interrogate subject matter experts and make them explain things for the rest of us and inspectors" mode.

Well that press conference was a waste of time. Blah, blah, waffle, forget or ignore the question.

But what I am also also suggesting is that if this is the case, I’m sure this has been factored in to the MHRA’s decision to green light the 12 week regime – there may be a public health case.

agreed Im sure they have an idea of what the trade off might be having over-exagerated how quickly vaccine can be rolled out its a trade off I bet Johnson is more than happy to take

Interesting graph that. I’m just a physician and haven’t done stats since med school, but it looks to me like one dose results in pretty darn good protection 14 days later that starts to reduce after 12 weeks. However as pointed out there aren’t very many events (infections) so it will have wide confidence intervals. As a volunteer in the Oxford trial we’ve been doing weekly PCR and continue to do so for at least the next 6 months so more data will come about that and I guess the same is true of the Pfizer trial albeit only if symptoms. That part (no asymptomatic testing) does seem a bit odd. There would be more events with more testing.

Reading that paper properly, I'm inclined to agree TiRed - inferring 1 dose efficacy using the 14-21 day window alone is in the best technical term I can come up with, properly dodgey.

docrobster - that's not a 1 dose treatment arm - they actually got the second dose at 21 days if I'm reading the paper correctly. It's just a poorly formatted/presented plot.

Not sure if this comment on the Pfizer trial has been commented on by our experts- twentyfold suspected v. confirmed infections. https://blogs.bmj.com/bmj/2021/01/04/peter-doshi-pfizer-and-modernas-95-effective-vaccines-we-need-more-details-and-the-raw-data/

properly dodgey

I was shouting “it’s a hunch”, at the TV.