Covid-19 Gambles

[JohnW2]

Yes, my mistake. You are correct.

I'm glad you agree.

In light of this high efficacy, I'm finding it hard to reconcile the current seemingly 50/50 or so split in hospitalizations. Is this to be expected or not?

On the basis of what we have been told, it sounds very 'unexpected' to me! Where does your 50/50 figure from - I 've not been having much success in finding useful data.

On 1st July ("Covid-19 vaccine surveillance report: Week 26") published the following, but it seems to be a summary of the published trial data, not actual UK experience. Dmittedly, as it says the below figures relate exclusively to the alpha variant but, although one would expect figures to be a bit worse with delta, on the basis of 'what we have been told', I would not expect that to result in the dramatic difference between what the below figures and your "50/50". Mind you, if it were the case that appearance of a new variant had made such a dramatic difference, it would certainly undeline my feeling that we should be trying to keep the prevalence low, to reduce the chances of any new variant emerging.

.

Anecdotally, I do know a few people who have Covid at the moment, and they've all been vaccinated. And Sajid Javid, of course (but we're not acquainted!).

I suppose because it's in their nature, anecdotes definitely vary. I know of 5 people who currently have Covid. All are under 40. Two have had one dose of vaccine and the other three have had no doses. We must't read too much into anecdotes

Kind Regards, John

 

[JohnW2]

Yes, I think we agree on this. (!)

That's good to hear!

My point about mumps was that can affect male fertility, so that is clearly not a reason per se for females to take it, but mumps is a horrid experience whoever you are, as I can attest.

Yes, but I think you miss my point. Mumps vaccine is given because (both for females and males), the disease can, and does, kill (I think around 100 per million cases) (as well as being able to do lots of other nasty and unpleasnt things, particularly in adults!) and, given that the vaccine is very safe, the risk-benefit is very much in favour of the vaccine for the recipient's own protection - it is not to 'protect some third party (as with rubella vaccine).

Kind Regards, John

 

[JohnW2]

As a well vaccinated person, I shouldn't think so.[=/quote]Fair enough.
Some work better than others. Some are very safe and effective. Some have been withdrawn. Some use novel technology. Some have only emergency use authorization.

All true, but I can't see that a response to any of it is required.

The miracle is that we managed to develop and test any vaccines which were fairly effective and very safe (certainly short-term), let alone deploy it so rapidly (WHO reports over 3.4 billion doses administered globally as of yesterday) within the time-scale it has happened. I'm used to seeing a decade or more from initial conception to approval of a new medicine!

There may, of course, be harmful effects of any of the vaccines in the long term, but we have no choice but to accept that risk - and, in any event the same theoretical risk exists with Covid-19 infection if one doesn't get vaccinated. The pandemic of encephalitis lethargic which followed the 'Spanish Flu' epidemic of 1919 was followed by a Parkinson's Disease like illness arising anything up to 40-50 years later in many of those who had been infected with the virus way back.

Kind Regards, John

 

[Swwils]

As expected the biggest ever flu programme will roll out this year.

https://www.gov.uk/government/news/biggest-flu-programme-in-history-to-roll-out-for-winter-2021

 

[JohnW2]

As expected the biggest ever flu programme will roll out this year.

Indeed, and presumably very wise.

There is still talk of it being combined with booster (3rd) doses of Covid vaccine, at least for the 'most vulnerable' (like me, I suppose!) but I imagine that, even in terms of the current vaccines, there will be difficulty in deciding which vaccine to give, given that the results of 'mixed vaccines' trials will probably/presumably not be available in time.

Kind Regards, John

 

[JohnW2]

On 1st July ("Covid-19 vaccine surveillance report: Week 26") published the following, but it seems to be a summary of the published trial data, not actual UK experience. Dmittedly, as it says the below figures relate exclusively to the alpha variant but, although one would expect figures to be a bit worse with delta, on the basis of 'what we have been told', I would not expect that to result in the dramatic difference between what the below figures and your "50/50".

I didn't look far enough down the report. In a slightly illogical place, I found (this from the latest 'Week 28' report), which doesn't seem to go anywhere near being consistent with echoes' "50/50" suggestion ...

Kind Regards, John

 

[Notch7]

On the absolute number of cases, we must know what the denominator is, or else that number is pretty meaningless. For context, the UK is conducting as many daily tests as the rest of Europe combined

I don’t know why positive case numbers are constantly referred to - and comparisons made with other countries…..as the absolute figure is meaningless.

The only thing that counts is positive rate…ie so many per thousand people etc.

 

[JohnW2]

I don’t know why positive case numbers are constantly referred to - and comparisons made with other countries…..as the absolute figure is meaningless. ... The only thing that counts is positive rate…ie so many per thousand people etc.

Sure. No matter what metric one is looking at, comparisons between countries must be undertaken on a 'per capita' basis, and hopefully that's what any sensible person comparing countries does. If one is only looking at changes within a single country, that's obviously not an issue.

As for 'which metric', there is no ideal. Particularly given the significant component of asymptomatic infections, 'positive case numbers' depend critically on how many tests are undertaken, and on whom (and for what reasons) - and than can vary considerably between countries.

One might think that 'Covid deaths' would be a pretty hard metric but, as I've said, there is considerable variation between countries (and even within some countries, like the UK) in how such deaths are defined, so even those figures have to be viewed with caution. It is probable that (for different reasons) all of the indices of 'Covid-19 deaths' in the UK over-estimate the number of deaths that can be 'reasonably' attributed to Covid (although the PHE's "28Days" Covid Detah figures may possible under-estimate).

In overall society terms, the least controversial metric is the number of excess deaths (i.e. including all deaths consequent upon existence of the pandemic, and responses to it, rather than directly due to Covid), but that is of no use if one's interest is in following changes/evolution of the actual Covid epidemic within a country.

In a country such as ours, the number of patients 'hospitalised with Covid' is probably a better index of changes in the situation than one might think since (unless things become dire) the clinical criteria for hospital admission will remain fairly constant, as will the proportion of Covid case in which it is not felt (by patient or healthcare professionals) appropriate to consider hospitalisation.

But, as with so many of these things, there is no 'right' or 'wrong' answer - just a choice between various imperfect ones.

Kind Regards, John

 

[JohnW2]

You know that's simply not true when prevalence is low, and of the same order of magnitude as the actual FPR. ... E.g. Prevalence of 1%, FPR 0.5%, would mean that 33% of the positive results are false. ... False negatives dominate at high prevalence.

No argument with that, but it does get a bit more complicated when one realises that the 'prevalence' relevant to that statement is the (unknown) prevalence in the population tested, which depends critically on who is tested, and why - factors which equally affect the pre-test probability of a positive result.

However, although what I wrote to EFLI was highly simplified (I already 'write far too much') the point I was trying to get across is that we have nearly always been in a situation in which at least prevalence in the community (as above, goodness knows about the 'tested population') was 'pretty low', and not changing all that much from day to day, such that changing prevalence would not result in a lot of distortion of the pattern of day-to-day changes due to false positives. There have been quite long periods when we would have thought of a daily increase in reported cases of, say, 1,000 as being 'high', but with around 1 million tests per day, that's only a 0.1% increase in prevalence (in the tested population).

However, more generally, something about the figures doesn't seem to add up ...

It's difficult to find any hard data about the performance of the tests, which I suppose is understandable, given that the absence of a 'gold standard' means that we are reliant on purely laboratory work (which may not accurately reflect 'in the field' performance) and/or replicate testing. However, many people seem to talk about a FPR of around 1.0 - 1.5% (and the ONS once quoted "0.8% - 4.3%", which is perhaps an indication of how uncertain this all is).

For the last 4 months or so, in round figures we have been seeing the results of about 1 million tests each day, and for quite substantial proportion of that period there have been around, or below, 2,000 positive tests per day - and it seems inconceivable that anything like all of them could be 'false positives'. If only half of them were 'true positives', that would imply an FPR of only about 0.1% and since I believe that even that assumption is very improbable, I would think that the implied FPR would be appreciably less than 0.1%.

For those who assume a higher FPR, say 2%, we would (with ~1m tests per day) seeing about 20,000 positive tests today which were 'false positives', hence that number of positive tests even if there were zero true prevalence (in the tested population) - but it's only quite recently that the total of ('false' and 'true') positive results has been as high at that.

The only rational conclusion I can think of is that the FPR (in the populations we've been testing) must be very low, probably lower than any suggestions I've seen - but even that seems unlikely.

"Discuss" !!

Kind Regards, John

 

[JohnW2]

The UK (and everywhere else) will achieve herd immunity one way or another. Whether vaccination plays a significant part of this outcome is unknown, but with significant numbers of cases and hospitalizations among the vaccinated, it's looking like immunity via exposure is more reliable.

Looking back, I didn't really respond to that suggestion.

I'm no virologist or immunologist but, from what little I know about those subjects, my intuitive view would probably be as you suggested - that exposure to an entire pathogen (by their millions/billions) when infected would result in a more robust immune response than does targeting 'just a few little bits' of the pathogen with a vaccine. However, my intuition is presumably wrong, because those who know much more than I do (essentially JCVI) have consistently advised that even those who have had laboratory-confirmed severe Covid-19 infection should nevertheless still be vaccinated.

I see that @Swwils has been around again, so I wonder if he can perhaps shed some light on this?

Kind Regards, John

 

[mikeey84]

The only rational conclusion I can think of is that the FPR (in the populations we've been testing) must be very low, probably lower than any suggestions I've seen - but even that seems unlikely.

David Speigalhalter, one of the most rational voices during the pandemic, agrees with you.

Speaking to the BBC, Professor David Spiegelhalter from the University of Cambridge said that the figure touted for a false positive rate of 0.8 per cent “seems far too high” when looking at other ONS surveys.

“The ONS survey [from June] did 112,000 tests and only got 50 positive tests out of it," he said, noting that even if all of these were false positives, the rate would be under 0.05 per cent.

 

[JohnW2]

David Speigalhalter, one of the most rational voices during the pandemic, agrees with you.

That's reassuring (and somewhat 'flattering') because, I like you, I regard him as "one of the most rational voices during the pandemic".

Speaking to the BBC, Professor David Spiegelhalter from the University of Cambridge said that the figure touted for a false positive rate of 0.8 per cent “seems far too high” when looking at other ONS surveys.

Exactly - but I don't claim that either he or I have been applying any 'rocket science' ...

... as I recently wrote, we went through a significant period of time when there were around or below 2,000 positive tests per day out of around 1 million tests per day.

Had the FPR been 0.8%, there would have been about 8,000 (all 'false') positive tests per day even if no-one was infected (which is obviously a ridiculous assumption) - so something is obviously 'wrong'. The number of tests and the number of positive results are presumably roughly 'right' - so, as far as I can see, that seems to really only leave the assumed FPR to be 'very wrong'.

What rather amazes me is that the ONS and many others persist in quoting these 'high' FPRs when, at least to my mind, it is pretty obvious that they can't possibly be correct!

Kind Regards, John

 

[Swwils]

Looking back, I didn't really respond to that suggestion.

I'm no virologist or immunologist but, from what little I know about those subjects, my intuitive view would probably be as you suggested - that exposure to an entire pathogen (by their millions/billions) when infected would result in a more robust immune response than does targeting 'just a few little bits' of the pathogen with a vaccine. However, my intuition is presumably wrong, because those who know much more than I do (essentially JCVI) have consistently advised that even those who have had laboratory-confirmed severe Covid-19 infection should nevertheless still be vaccinated.

I see that @Swwils has been around again, so I wonder if he can perhaps shed some light on this?

Kind Regards, John

Interesting question. Very complex discussion surrounds this - not only because the analogous and important discussion of: is there any difference in length if protection via vaccine or a natural infection? For instance the natural immunity from HPV infection is massively weaker than the vaccine's.

However the entire point of the vaccine is to produce robust immune response. In particular with these mRNA based vaccines the resulting antibody levels are very very good. We have come a long way from cow pox...

The initial data suggests that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection. So these antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the target domain.

Those with infection immunity only may have differing levels of protection to emerging SARS-CoV-2 variants and I believe this is what underpins the strategy to vaccinate those who even have been previously infected.

Why this happens is up for debate, the mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced.

Or it could be a natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe) and the vaccine via muscle could give a more thorough immune responce.

Certainly in some circumstances and individuals the virus could be cleared before any real T or B cell involvement, so effectively might not have any persistent immunity at all.

 

[JohnW2]

Interesting question. Very complex discussion surrounds this - not only because the analogous and important discussion of: is there any difference in length if protection via vaccine or a natural infection? For instance the natural immunity from HPV infection is massively weaker than the vaccine's.

Many thanks - that all makes total sense, even to little me

However, what you actually write is not necessarily as reassuring to me personally as it might be. Everything you say seems to relate to mRNA vaccines, whereas I have had two doses of AZ vaccine. Is the potential advantage of vaccine over 'natural immunity' less in the case of a 'traditional' vaccine, I wonder?

Kind Regards, John

 

[Notch7]

John -this thread is very interesting -the debate is scientific which has so far avoided the emotive, political arguments that fester most covid threads