When will this shit end?

[Fuzzy Afro]

2 minutes ago, stuartbert two hats said:

No, I meant AZ is slow to kick in. It takes 8-12 weeks to get full protection, much slower than Pfizer.

Where have you seen that? I know that AZ is more effective with the longer gap if that's what you mean.

[Fuzzy Afro]

Also worth noting that lockdown has basically caused this third wave. If we'd gone ahead and reopened fully on 12th April we'd have had a moderately sized exit wave but probably not overwhelmed the NHS, but with the advantage of having achieved herd immunity before Delta got here.

[Ozanne]

It’s a shame we allowed the Delta variant in all for a trade deal. 

[stuartbert two hats]

2 minutes ago, Fuzzy Afro said:

Where have you seen that? I know that AZ is more effective with the longer gap if that's what you mean.

I've not looked at the data comparing the two for a while - it all gets a bit mixed up with the reporting on whether two doses is actually the important factor or whether the timing is more important. So I'm up for seeing the data in more detail if anyone has anything recent - I may have things wrong. 

Having said all that, I could have sworn that the mRNA vaccines now have a shorter gap between the two doses in the UK, but a quick Google hasn't brought up anything to support that - there's a lot out there. I might have just got my wires crossed between advice I've read and actual practice here.

[Toilet Duck]

31 minutes ago, zahidf said:

If that's the case, let's use the spare AZN and drop the under 40 ban

As has been noted by a few posters above, the risk:benefit ratio for AZ (and J&J) in younger cohorts is shifting as cases increase. It’s also shifted on another front. Despite the hesitance by some, the proper investigation of the underlying pathology of the clots and communication of this to medical professionals has led to the robust early diagnosis and treatment of the clots when they do (in rare instances) arise. So, the incidence of clotting events in Europe as these vaccines have continued to be used hasn’t changed…however, mortality from them has dropped, shifting the risk lower again and strengthening the argument for more widespread use (they are currently available in younger age groups here by consent, but we still have way more Pfizer, so there’s not much spare AZ/J&J anyway…we are due a stack at the end of June/start of July, so we’ll see what happens)…this is why it was important to be transparent and to look into this thoroughly, as it means we can use them in a safer manner (and if the Germans are correct, a quick tweak of the vaccine might fix it altogether)…

[stuartbert two hats]

5 minutes ago, Fuzzy Afro said:

Also worth noting that lockdown has basically caused this third wave. If we'd gone ahead and reopened fully on 12th April we'd have had a moderately sized exit wave but probably not overwhelmed the NHS, but with the advantage of having achieved herd immunity before Delta got here.

Citation needed

 

[Fuzzy Afro]

Just now, stuartbert two hats said:

I've not looked at the data comparing the two for a while - it all gets a bit mixed up with the reporting on whether two doses is actually the important factor or whether the timing is more important. So I'm up for seeing the data in more detail if anyone has anything recent - I may have things wrong. 

Having said all that, I could have sworn that the mRNA vaccines now have a shorter gap between the two doses in the UK, but a quick Google hasn't brought up anything to support that - there's a lot out there. I might have just got my wires crossed between advice I've read and actual practice here.

 

That's not quite right, I'll need @Toilet Duck to confirm but this is my rough understanding of it:

 

1. Pfizer and Moderna originally recommended 3 week gaps, purely because this was the gap used in the trial and they hadn't tested out any longer gaps.

 

2. AstraZeneca recommended a 12 week gap, because they'd accidentally stumbled across it in the trial due to some mistake where a small number of participants were given 1.5 doses rather than 2 and it turned out better for the 1.5 dose group.

 

3. UKG started ramping up the vaccine programme in early January after a soft launch in December and employed the 12 week strategy to get as many people protection as possible (The Kent variant, dominant at the time, was very well protected by just 1 dose with the 2nd just being there to provide longer term immunity, so made sense to give twice as many people one dose rather than using the shorter gap used in the States and elsewhere). This was seen as a gamble for those getting the Pfizer as it hadn't been trialled with a 12 week gap although subsequent analysis has showed that it provides more antibodies with the longer gap as per AZ.

 

4. Some time around mid-May when we started to see the Delta variant change the equation, the JCVI recommended the gap be cut from 12 weeks to 8 for those in groups 1-9. This is because the Delta variant is better at beating the vaccine when you've only had one dose and you really need the second one to be properly protected, unlike the Kent/Alpha variant where the first dose cigars it. The 8 week gap was used regardless of what vaccine you had.

 

 

 

 

[Fuzzy Afro]

10 minutes ago, stuartbert two hats said:

Citation needed

 

Give this thread a read

 

 

[stuartbert two hats]

4 minutes ago, Fuzzy Afro said:

 

That's not quite right, I'll need @Toilet Duck to confirm but this is my rough understanding of it:

 

1. Pfizer and Moderna originally recommended 3 week gaps, purely because this was the gap used in the trial and they hadn't tested out any longer gaps.

 

2. AstraZeneca recommended a 12 week gap, because they'd accidentally stumbled across it in the trial due to some mistake where a small number of participants were given 1.5 doses rather than 2 and it turned out better for the 1.5 dose group.

 

3. UKG started ramping up the vaccine programme in early January after a soft launch in December and employed the 12 week strategy to get as many people protection as possible (The Kent variant, dominant at the time, was very well protected by just 1 dose with the 2nd just being there to provide longer term immunity, so made sense to give twice as many people one dose rather than using the shorter gap used in the States and elsewhere). This was seen as a gamble for those getting the Pfizer as it hadn't been trialled with a 12 week gap although subsequent analysis has showed that it provides more antibodies with the longer gap as per AZ.

 

4. Some time around mid-May when we started to see the Delta variant change the equation, the JCVI recommended the gap be cut from 12 weeks to 8 for those in groups 1-9. This is because the Delta variant is better at beating the vaccine when you've only had one dose and you really need the second one to be properly protected, unlike the Kent/Alpha variant where the first dose cigars it. The 8 week gap was used regardless of what vaccine you had.

 

 

 

 

Yeah, that sounds right. I've mixed up data from Israel and the US on how Pfizer has been used there. I don't think we're using different gaps here.

I think we probably should though.

[Fuzzy Afro]

2 minutes ago, stuartbert two hats said:

Yeah, that sounds right. I've mixed up data from Israel and the US on how Pfizer has been used there. I don't think we're using different gaps here.

I think we probably should though.

Different gaps between Pfizer and AZ? Why?

 

It's a trade-off between a longer gap which has the advantage of a better antibody response (and also getting more people partially vaccinated in a shorter time, although that's less of an issue now that we're in the final stage of first doses) and a shorter gap which has the advantage of fully-vaccinating people more quickly given we have a variant on the loose that is good at escaping the first dose (but not as escaping in fully vaccinated people). This is true of both Oxford and Pfizer as far as I'm aware.

 

IMO, at this stage we need to be getting people fully vaccinated ASAP. That means speeding up outstanding second doses and probably vaccinating younger adults and children with a very short gap. This will probably have long term consequences as the total immune response will be less so we will need to give these people boosters eventually but on balance it's probably better to kick the can down the road than risk having a choice between maintaining restrictions through the summer or an exit wave with 10,000 fatalities.

[stuartbert two hats]

Just now, Fuzzy Afro said:

Different gaps between Pfizer and AZ? Why?

 

It's a trade-off between a longer gap which has the advantage of a better antibody response (and also getting more people partially vaccinated in a shorter time, although that's less of an issue now that we're in the final stage of first doses) and a shorter gap which has the advantage of fully-vaccinating people more quickly given we have a variant on the loose that is good at escaping the first dose (but not as escaping in fully vaccinated people). This is true of both Oxford and Pfizer as far as I'm aware.

 

IMO, at this stage we need to be getting people fully vaccinated ASAP. That means speeding up outstanding second doses and probably vaccinating younger adults and children with a very short gap. This will probably have long term consequences as the total immune response will be less so we will need to give these people boosters eventually but on balance it's probably better to kick the can down the road than risk having a choice between maintaining restrictions through the summer or an exit wave with 10,000 fatalities.

Do you not remember the initial efficacy trials for AZ which showed it to be considerably less efficacious than the mRNA vaccines after 3 weeks? Pfizer just kicks in more quickly.  They were only ever aligned because we wanted to get more first doses jabbed and made an educated (correct) guess that it wouldn't be worse with a longer gap.

It just doesn't need as much time for the b-cells to mature.

[stuartbert two hats]

You double jab people with AZ after three weeks and you'll impact their long term protection. Not so with Pfizer.

[Fuzzy Afro]

1 minute ago, stuartbert two hats said:

Do you not remember the initial efficacy trials for AZ which showed it to be considerably less efficacious than the mRNA vaccines after 3 weeks? Pfizer just kicks in more quickly.  They were only ever aligned because we wanted to get more first doses jabbed and made an educated (correct) guess that it wouldn't be worse with a longer gap.

It just doesn't need as much time for the b-cells to mature.

 

I was under the impression that it was less efficacious when the gap between doses was 3 weeks, rather than less efficacious 3 weeks after the first dose. Could be wrong though. Sure @Toilet Duck will tell us 

[zahidf]

26 minutes ago, Ozanne said:

It’s a shame we allowed the Delta variant in all for a trade deal. 

Well we have loads of Indian citizens who went back to India for funerals in that time.

I appreciate hindsight but it wasn't all just for a trade deal. Lets not get too nigel farage about it.

[zahidf]

16 minutes ago, Fuzzy Afro said:

Give this thread a read

 

 

He's an economist... who also spent most of yesterday having a go at BLM...

He's not stupid but he isn't really an expert on epidemiology or race relations

[Gingerfish79]

1 hour ago, BobWillis2 said:

One thing the government must show on Monday is what level of risk and death we have to accept going forward. 

We need something to base everything off, is opening on the 21st going to put us above that level? Is a 2 week delay going to keep us below that level? If not what is. 

Not sure even Boris is dumb enough to go on record and say the death of x number of British citizens is acceptable. 

[stuartbert two hats]

2 minutes ago, Fuzzy Afro said:

 

I was under the impression that it was less efficacious when the gap between doses was 3 weeks, rather than less efficacious 3 weeks after the first dose. Could be wrong though. Sure @Toilet Duck will tell us 

It's been a while since those trials, agreed TD will be able to explain properly what the data did and did not say.

[Ozanne]

4 minutes ago, zahidf said:

Well we have loads of Indian citizens who went back to India for funerals in that time.

That’s a good point, even more reasons India should’ve been put on the red list along with Pakistan and Bangladesh. 

Edited June 9, 2021 by Ozanne

[Ozanne]

Interesting thread:

 

[Fuzzy Afro]

Blackburn with Darwen will be getting twinned with Wuhan at this rate. It’s absolutely off the charts. 

[MrBarry465]

1 hour ago, Ozanne said:

2 of the 3 of those have no impact on June 21st going ahead or not. 

He's a hopium addict.

[Fuzzy Afro]

8 minutes ago, MrBarry465 said:

He's a hopium addict.

Ozanne talking shit as usual.

 

Point 1, the link between hospitalisations and deaths is a key factor in 21 June going ahead.

 

Point 2, I agree is moot since protections won’t kick in by the 21st.

 

Point 3 on the economy absolutely is a factor. 

[Toilet Duck]

Crikey…I watch a quick Seinfeld before bed and there’s a ton of questions when I pick the phone back up! 
 

so…gaps and efficacy. For the mRNA ones, optimum gap is about 4 weeks, after that the antibody levels start to dip a bit. There was a trade off in the UK between more jabs and dwindling protection from 4-12 weeks, but any protection was better than none and it doesn’t appear to harm long term immunity if dose 2 is given later (as you would expect, but nice to know for sure). Almost everywhere else is using these vaccines with a 3-4 week gap (we use Pfizer with 4, Moderna with 3 or 4 as it’s currently mostly being used in pregnant women, so it depends on when the clinics are scheduled)…I’d do the same thing in your current position now (since 2 dose > 1 dose for delta)…

For AZ, there was a screw up in the trial where some participants got a half dose for their first one by accident (manufacturing issue in Italy I believe)…but, both LD:SD and SD:SD participants got varying gaps between doses (for a variety of reasons). When the data was first unblinded, AZ stormed ahead and said they had ~70% efficacy and it could be as high as 90%+ (with a half dose). By the time the authorisation submission was made, Oxford had fully analysed the data and saw that it was the longer gap that improved efficacy rather than the different doses (as SD:SD participants with a longer gap had better antibody responses too). This was all fairly clearly explained in the submission for emergency use authorisation. The increase in antibody response starts to plateau at about 8 or 9 weeks and there isn’t much additional benefit after that. But, some participants had waited up to 12 weeks to get their second dose. So when prioritising 1st doses, JCVI figured they could safely go to 12 weeks and, again, like the extended gap with Pfizer, get some protection into more people (as well as improving the effectiveness of AZ)  Most other places using AZ have gone with a similar gap (I think I said at the time I’d probably go for 8 or 9). At about 6 weeks, the response is still not that far off, so where full vaccination was required quickly, this gap has been used (for example, many healthcare workers here that got AZ had a 6 week gap…and cases have fallen off a cliff among them). So, quickest route to full vaccination with the vaccines ye have is probably, Pfizer with a 4 week gap, Moderna with a 3 week gap, AZ with an 8 week gap (6 if you have to) and one shot of J&J (or any vaccine) in people with PCR confirmed Covid in the last 9 months (as we get more data, that could extend out to ever having PCR confirmed Covid)…

As for the “if we were still only dealing with the Kent variant, R would be below 1” thing, it’s very hard to untangle that…delta is outcompeting it, so of course alpha cases are dropping. How much of that is vaccination or competition with a fitter variant is incredibly hard to model. I dare say a beta or gamma outbreak in a vaccinated population would outcompete delta (but luckily those outbreaks had to compete with alpha in a mostly immunologically naive population…would be a different proposition now and they are fitter variants in a vaccinated cohort due to superior vaccine escape compared to delta or alpha)...

 

edit: sorry, forgot to tag @Fuzzy Afro and @stuartbert two hats

 

Edited June 9, 2021 by Toilet Duck

[Toilet Duck]

2 hours ago, BobWillis2 said:

One thing the government must show on Monday is what level of risk and death we have to accept going forward. 

We need something to base everything off, is opening on the 21st going to put us above that level? Is a 2 week delay going to keep us below that level? If not what is. 

I think Chris Whitty has pretty much already done that and said that a CFR in the ballpark of seasonal flu is one we would need to accept (the alternative is elimination followed by eradication…the first could take a decade of travel restrictions at least, the latter may never be attainable)…and it does look at the moment like the vaccines will get us to that point (current CFR is bang on seasonal flu, but cases aren’t distributed as evenly across age groups for a direct comparison…maybe that’s full vaccination in the higher risk cohort, or maybe as cases rise we’ll see more fully vaccinated older patients turning up in hospital and ultimately succumbing to it…it doesn’t look like that at the moment, so hopefully it stays that way…just need a bit more time to see how it develops…it’s still all pointing in the right direction on that front though)…but more of the population needs to be fully protected to make sure of that…I think if you have over 40s fully vaccinated (and maybe one dose in under 40s, especially since there is more natural infection already in this group), the CFR should stay near flu (it’s about 0.15% in the UK at the moment and vaccine-controlled flu is usually 0.1-0.2%…really need to see if seasonality impacts on this though…of course case load then impacts on the CFR, so if Covid cases vastly outstrip typical flu case loads, then it ends up with higher mortality. They both have similar secondary attack rate ranges though (5-15% depending on the circulating flu strain) so I’d like to think that wider vaccination for Covid will keep a lid on things better than we do for flu since lots of people don’t bother to get vaccinated for that). 

So, based on vaccination schedules, when you reach that point (40+ fully vaccinated) should be predictable. After that, the main variables left in there then are hospital admissions in younger unvaccinated/partially vaccinated folks (even short stays impact indirectly on patient care elsewhere in the hospital…if this is a problem, then finishing the vaccination programme is the point where all restrictions go, if not, then we’re ok before that…and that’s pretty close to where we are now), long Covid (I know some of you think it is hypochondriac nonsense, but until we have robust reporting of it, it’s an unknown burden and one that is also taken out of the equation by finishing the vaccination programme) and the aforementioned seasonality (which is a black box at the moment). 

[JoeyT]