Oxford Vaccine - What Does “70% Effective” Mean?

[Davef]

It is of course dangerous to make such assumptions. For example you could have a virus that originally infects 3 people per original infection. You bring in hand washing and it drops from 3 to 1. Then there is a mutation and it doubles from 1 to 2. If this was because the mutation made the virus more resistant to hand washing then removing the hand washing regime would not cause the original number to jump from 3 to 6.

[ian]

I'll repeat Box's original adage: all models are wrong, but some models are useful. That includes epidemiological models. He was expressing the point that models are just that, they're potentially useful approximations of reality based on the selected parameters. There's no innate correctness or truth in them. Change the parameters and the model changes. So all models like this should be interpreted with caution and not as absolutes. Evidence for new more transmissible variant came from models, not (as far as I know) experiment. You can't properly separate transmissibility of the virus itself from people's behaviour in creating events that make transmission possible.

[simonp]

Sorry I was not saying an increase from 0.4 to 0.7. I was saying an increase in the range [0.4-0.7] Or if you prefer 0.55 give or take absolute increase to the current effective R

This was an increase of between 40% and 80%

If the basic R0 went up from 3.0 by a similar % it would be in range [4.2-5.4]

0.4 to 0.7 i.e. the increase is somewhere between 0.4 and 0.7. So for instance if R_e is 1.0 and you increase by 0.4 to 0.7 then R_e is now 1.4-1.7.

1.4-1.7 from 1.0 is consistent with 50% (i.e. 1.5).

[simonp]

It is of course dangerous to make such assumptions. For example you could have a virus that originally infects 3 people per original infection. You bring in hand washing and it drops from 3 to 1. Then there is a mutation and it doubles from 1 to 2. If this was because the mutation made the virus more resistant to hand washing then removing the hand washing regime would not cause the original number to jump from 3 to 6.

Given that the new variant appears to have a higher viral load, the most likely explanation for easier transmissibility is simply greater shedding of virus. This would imply all measures need to be strengthened in order to have the same effect.

[sojournermike]

K can check, well I’ll have to later for work, but iirc the Imperial paper suggested a geometric increase in R with best estimate at 1.74 (yes not really that accurate!)

Given we don’t know what R0 is really, but new variant seems to give much higher viral loads in nasal passages and throat - likely at least on driver of increased transmissibility - unconstrained R’0 may well be above 4. Fauvism has been pushing his penetration numbers up recently - now at 85% and still admitting that he’s capping himself to not crush public hope/opinion

To be clear, I’m not a virologist or immunologist:)

[ian]

Where is the evidence of increased viral loads coming from?

[simonp]

Where is the evidence of increased viral loads coming from?

https://www.medrxiv.org/content/10.1101/2020.12.24.20248834v1.full-text

[Davef]

Where is the evidence of increased viral loads coming from?

From the pcr testing. One of the 3 markers tested, one is missing in the variant so you can identify track and trace tests that have 2 out of 3 targets matched and look at levels.

Oddly increased viral load seems geographical - for the variant it does not appear in tests in Greater London but does in Kent and other areas outside London.

[ian]

Thanks, my preprint-fu wasn't working and I couldn't find anything published.

It's somewhat speculative though (it's an interesting coincidence) that we only really detect this variant because it fails one of the PCR tests so we can chart its progress, we obviously don't do whole genome sequencing at levels to make this possible, there will be lots of other variants that we generally don't know much about unless they get sequenced).

A couple of caveats, there are potential limitations on the methodology they discuss. It's worth pointing out that the presence of viral RNA is not necessarily correlative of viral load. If the variant does result in more virus, then there's a counter to transmissibility – it's more likely to be detected in samples and so will appear more prevalent.

I'm mildly sceptical on whether there's a variant with significantly increased transmissibility (now usually reported uncritically) given that the main current evidence is epidemiological modelling. There are several equally compelling explanations (methodology as discussed, human behaviour, and viral population genetics).

[sojournermike]

I agree that behaviour, which I have only anecdotal information on, is probably a driver for current rising infection, hospitalisation and mortality rates. At this stage I’m reasonably comfortable that there is reason to consider that the new variant is more transmissible, but perhaps more importantly that we should act to control the worsening situation quickly and not ‘in due course’ when it’s got even worse.

[Davef]

U.K. does fully sequence quite a lot of positive tests - about  5% I believe.

[ian]

I agree that behaviour, which I have only anecdotal information on, is probably a driver for current rising infection, hospitalisation and mortality rates. At this stage I’m reasonably comfortable that there is reason to consider that the new variant is more transmissible, but perhaps more importantly that we should act to control the worsening situation quickly and not ‘in due course’ when it’s got even worse.

Well, I do worry a little that we're blaming the virus for the fact that it's spreading. Regardless of transmissibility, it is providing an interesting way of exploring the epidemiological spread (think of it in ecological terms, if you tag a small proportion of your favourite animal, we effectively have a clearly tagged viral variant). Debate aside, we're clearly providing ample transmission paths despite any claims of lockdown, and that is behaviour.

Davef mentioned it earlier, but our behaviour itself generates a selection pressure and helps not only spread a variant but determine the phenotypic qualities of that variant.

[sojournermike]

I agree that behaviour, which I have only anecdotal information on, is probably a driver for current rising infection, hospitalisation and mortality rates. At this stage I’m reasonably comfortable that there is reason to consider that the new variant is more transmissible, but perhaps more importantly that we should act to control the worsening situation quickly and not ‘in due course’ when it’s got even worse.

Well, I do worry a little that we're blaming the virus for the fact that it's spreading. Regardless of transmissibility, it is providing an interesting way of exploring the epidemiological spread (think of it in ecological terms, if you tag a small proportion of your favourite animal, we effectively have a clearly tagged viral variant). Debate aside, we're clearly providing ample transmission paths despite any claims of lockdown, and that is behaviour.

Davef mentioned it earlier, but our behaviour itself generates a selection pressure and helps not only spread a variant but determine the phenotypic qualities of that variant.

Reaches for the like button... yep, we’re still providing transmission paths.

An anecdotal example being the individual (nurse in elderly care setting) who joined parents for lunch on 25/12 after being tested late 23/12. Positive result returned early on 26/12. I’m still trying to make sense of this one really.

[chrisbainbridge]

An anecdotal example being the individual (nurse in elderly care setting) who joined parents for lunch on 25/12 after being tested late 23/12. Positive result returned early on 26/12. I’m still trying to make sense of this one really.

Lunacy!  We have 85 yr old patients with chronic lung conditions turning down vaccination!!!

[Morat]

70% is good.

But not as good as Dettol, which kills 99%

Lifebuoy soap is being advertised on the radio as killing "everything including Covid" . . .  but it tastes awful 

Is that the one that the Orange-utan was proposing we ingest?

[CrazyEnglishTriathlete]

70% is good.

But not as good as Dettol, which kills 99%

Does that mean that only 1 person in 100 survives drinking Dettol?

[Lightning Phil]

I agree that behaviour, which I have only anecdotal information on, is probably a driver for current rising infection, hospitalisation and mortality rates. At this stage I’m reasonably comfortable that there is reason to consider that the new variant is more transmissible, but perhaps more importantly that we should act to control the worsening situation quickly and not ‘in due course’ when it’s got even worse.

Agree, you keep your distance, the new variant can’t spread.  Anecdotal but I note that when people are meeting friends outdoors they are not socially distancing. Lucky if they are a foot apart let alone a minimum of 2m. Someone coming the other way, people continue on their straight path. Back in first lockdown you’d do the wide berth passing dance.  No longer, if a larger group forms, people aren’t making immediate steps to distance themselves. Dog walkers are some of the worst, being in each other’s faces as they pet  each other’s dog.

[Sergeant Pluck]

An anecdotal example being the individual (nurse in elderly care setting) who joined parents for lunch on 25/12 after being tested late 23/12. Positive result returned early on 26/12. I’m still trying to make sense of this one really.

Lunacy!  We have 85 yr old patients with chronic lung conditions turning down vaccination!!!

Is that because they want to wait for the Great British vaccine, as I have seen reported elsewhere?

Useful run-down on current thinking from the BMJ on the extending of dose intervals. My current understanding is that for the Oxford / AZ, there is good evidence to support extending, less so for the Pfizer.

https://www.bmj.com/content/372/bmj.n18?=&utm_source=adestra&utm_medium=email&utm_campaign=usage&utm_content=daily&utm_term=text&s=03

[sojournermike]

An anecdotal example being the individual (nurse in elderly care setting) who joined parents for lunch on 25/12 after being tested late 23/12. Positive result returned early on 26/12. I’m still trying to make sense of this one really.

Lunacy!  We have 85 yr old patients with chronic lung conditions turning down vaccination!!!

Is that because they want to wait for the Great British vaccine, as I have seen reported elsewhere?

Useful run-down on current thinking from the BMJ on the extending of dose intervals. My current understanding is that for the Oxford / AZ, there is good evidence to support extending, less so for the Pfizer.

https://www.bmj.com/content/372/bmj.n18?=&utm_source=adestra&utm_medium=email&utm_campaign=usage&utm_content=daily&utm_term=text&s=03

I think it’s fair to say that there’s some direct evidence supporting a longer gap for the AZ vaccine and no Direct evidence for or against in the Pf case. However, there is a lot of wider evidence from other vaccines that supports the approach. Further, I would assume that outcomes will be monitored - the issue here is one of how quickly immunity fades and whether the booster dose is still effective in ensuring long term immunity.

Some of the social media rhetoric is shocking - as usual.

[ian]

Immunologically, I don't think there's any case where delaying a booster has negative effects other than, of course, you spend a longer period without its protective effects of the second dose. Most people have sloppy adherence to vaccination programmes, get jabbed whenever, and yes, batches and types get routinely mixed up with evident ill-effect.

It's a valid point that we don't know, of course, but given the logistical challenge, as pointed out in that article, sometimes we have to take educated guesses. No vaccination means no protection at all.

[Lightning Phil]

An anecdotal example being the individual (nurse in elderly care setting) who joined parents for lunch on 25/12 after being tested late 23/12. Positive result returned early on 26/12. I’m still trying to make sense of this one really.

Lunacy!  We have 85 yr old patients with chronic lung conditions turning down vaccination!!!

Is that because they want to wait for the Great British vaccine, as I have seen reported elsewhere?

Useful run-down on current thinking from the BMJ on the extending of dose intervals. My current understanding is that for the Oxford / AZ, there is good evidence to support extending, less so for the Pfizer.

https://www.bmj.com/content/372/bmj.n18?=&utm_source=adestra&utm_medium=email&utm_campaign=usage&utm_content=daily&utm_term=text&s=03

I think it’s fair to say that there’s some direct evidence supporting a longer gap for the AZ vaccine

There is, the longer dosing regimes were used in part of the trials and it was the longer gap that saw a better immune response.  It’s all in the paperwork submitted, which you can see online. I don’t have a link right now, I was looking at it on Wednesday.

[Genosse Brymbo]

...
Most people have sloppy adherence to vaccination programmes, get jabbed whenever, and yes, batches and types get routinely mixed up with evident ill-effect.
...

ian, did you mean to write that, or is there a missing no?

[ian]

Yes, I did miss the no. My brain is up there, my fingers far, far away and now mostly autonomous republics.

[sojournermike]

I added the ‘no’ subliminally! Shows how conditioned we can be.

Yes, I’m aware of the AZ dosing regimes, but they were the result (in part at least) of mid ups. Hence, there is some evidence, but it doesn’t cover every age group for example. However, we are in agreement - using evidence from wider experience and sensible judgement is the appropriate approach.

I think there is, on balance, more sense and intelligence displayed in here than on Twitter, say. I accept that’s not a high bar.

[ian]

I miss words all the time. But it's true, my fingers are close to declaring independence from my brain. They were encouraged by the successful succession of my mouth.

But yes, I read a lot of arguments for perfection. Of course, we should follow the regimen from the trials. But reality sometimes requires imperfection and making the best decisions we can with the information we have. We don't have unlimited supplies of any vaccine, we know they will take time to arrive (and we are so, so lucky to have this – it's been amazing work on both the current vaccine platforms, bringing mRNA vaccines to fruition after decades of research, and an ample demonstration of a viral-vector platform – the latter was designed to make vaccines quick to develop and manufacture at low cost because it's not just about us in the first-world with funded healthcare systems).