The Lemon Fool

Nimrod103 wrote:I have seen many comments ... about the OxAZ vaccine having a lowered effect

Ditto. And hence my confusion. What does "lowered effect" mean? Chances of avoiding catching the virus, or the severity of the outcome if caught. or the transmissibility, etc. etc.?

VRD

Well that's me done (for now!). AstraZeneca 1 & 2.

vrdiver wrote:...
Does anybody have data on how effective the vaccines are on stopping hospitalisation and/or death for the current variants? ...
...
VRD

As promised here's the link to the English observational study which is the biggest study so far I think - https://www.medrxiv.org/content/10.1101 ... 1.full.pdf

Headline result is that "either dose <i.e. either the AZ or Pfizer first dose> is approximately 80% effective at preventing hospitalisation and a single dose of BNT 162b2 (Pfizer) is 85% effective at preventing death with Covid-19".

The absence of a conclusion re specifically the AZ vaccine and death is because the Pfizer vaccine was the one rolled out first so at the time of this paper in the authors' words "There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout of this vaccine" although since I assume (perhaps wrongly) that most Covid-19 deaths now occur in hospitals the AZ efficacy re hospital admissions seems to bode well for the deaths data that is probably now available since the data cut off for outcome data used in the linked report was 21st Feb 2021 and we are over a month on from that now.

I haven't dug up the NHS Scotland report but the results were very, very similar and the English report is analysing more people so seems the more interesting of the two given there is no significant divergence between the English and Scottish conclusions.

- Julian

Nimrod103 wrote:Seeing as most vaccines are targetting the same spike proteins, as present on the intial virus, one must surely assume they have similar effectiveness against the original virus, and similar reduced effectiveness against the Brazil/RSA variants?

I have seen many comments (and a very little evidence) about the OxAZ vaccine having a lowered effect against the Brazil/RSA variants, but I cannot recall seeing any comments or data regarding the effectiveness of Pfizer or Moderna.

Actually they are not the same spike proteins. I wondered that myself, i.e. if you took the spike protein as sequenced very early in the pandemic (even before it was officially declared a pandemic I think) would that be exactly the coding for the spike protein that you saw in all of these vaccines. The answer is no, not exactly the same.

This article - https://cen.acs.org/pharmaceuticals/vac ... -19/98/i38 - goes into some depth about how Moderna modified the spike protein that its vaccine codes for by inserting a couple of extra amino acids into the sequence at a key joint in the spike protein in order to keep it stabilised in the prefusion state, something thought to enhance vaccine efficacy. That article also explicitly mentions that J&J, Novavax and Pfizer have also made modifications to the original spike protein in order to try to keep it stabilised in its prefusion state. I can't remember where I read it but somewhere I saw (or maybe heard) that the AZ vaccine does not have modifications to try and lock the spike into the prefusion state and even if it does perhaps all the different vaccine manufacturers that attempt to stabilise the spike protein configuration all use different approaches where some might be more effective than others and/or the changes they have made might have differing effects on the nature of the antibody responses generated (i.e. exactly what the antibodies "see" when recognising the modified spikes. Also, the "real" spike protein is attached to the surface of the SARS-CoV-2 virus whereas the spikes generated by the mRNA and viral vector vaccines need to attach to the surface of human cells (mostly muscle cells). Does that require a change to the structure of the "tail" of the spike protein to account for it needing to bind to the different surface and if so might there be differences in terms of how convincing an impression of a "real" SARS-CoV-2 spike a vaccine spike is able to do? That's another question I would love to ask an immunologist.

On the second point re AZ efficacy the only evidence I have seen re reduced AZ efficacy against the SA strain is this small study that shows essentially none against mild or moderate disease and due to the young average age of the cohort yields no useful data at all on efficacy against hospitalisation or death - https://www.nytimes.com/2021/02/07/worl ... frica.html

I can't find any links right now but there has also been a fair amount of in-vitro work measuring the neutralising properties of AZ-generated antibodies against the SA strain vs against the original strain and the results show a multi-fold reduction in neutralising properties. In fairness reductions are also seen in Pfizer and Moderna in-vitro responses but I don't think it is at all clear yet how that translates into real-life protection in humans.

For some of the later vaccines some of the phase 3 trials had some percentage of the trial populations in Brazil and South Africa at times when these variants of concern were prevalent there. This article is a decent summary assuming it is an accurate report of the phase 3 trial results - https://www.forbes.com/sites/williamhas ... 0falls,1.1. I think searching specifically for the phase 3 trial results for those various trials will get you to the original reports that break out the phase 3 trial efficacy by country which gives some idea of the ranges of reduced efficacy vs the SA and Brazilian strains.

So basically all vaccines seem to be seeing reduced efficacy against the SA strain vs the original strain at least for mild and moderate illness but, for all except AZ which was only that one small trial, still efficacy similar to or better than a typical years' flu jab.

For the UK I hope this ends up all being a bit academic. As long as none of the E484K-carrying mutations become widespread in the UK in the next 6 to 9 months there will be boosters specifically targeting those variants fairly widely administered by that time and if the school of though that the convergence of independent mutations implies that the virus has a limited number of useful and viable mutations available to it and hence might have "run out of tricks" and already "played its best card" turns out to be correct then one round of booster jabs in the last quarter of 2021 really might to all intents and purposes slay this particular demon at least as far as the UK is concerned although much will be left to be done elsewhere in the world. Yes, we will then still be left with some nasty negative fallout in terms of NHS backlogs, interruptions to children's education and higher levels of debt but we will be left with some positives too, not least the accelerated progress in various areas of medicine that I hope will carry forward for many years to come and hopefully also numerous optimisations in the NHS and various critical supply chains and manufacturing processes that will also carry forward to give ongoing benefits. And the pubs will be open again!

- Julian

In the latest John Campbell video (https://www.youtube.com/watch?v=sni7e-2oGZk), he says that the evidence on the efficacy of all the available vaccines on the Brazil variant is very preliminary but looks as though it should still be very good (see talk at about 14mins15secs). He believes that vaccination will provide c.80 rather than c.90% protection againt catching the virus, and still provide 100% protection against death or serious disease.

He seemed remarkably chipper about the situation.

Surely one should give these figures in the context of jabs given.

So, deaths per 100,000 perhaps.

Best wishes,

Steve

Steveam wrote:Surely one should give these figures in the context of jabs given.

So, deaths per 100,000 perhaps.

Best wishes,

Steve

Yes, for deaths that would be way more helpful.

Bear in mind however that these figures are from Yellow Card reporting. I had a discussion with a friend of mine working on this stuff about the Yellow Card system last week which was interesting. Apparently it is pretty well accepted in the pharma industry that the Yellow Card system tends to under-report side effects and another issue is that even the data coming through from professional channels (GPs etc) is often very sparse and there is little additional background info accompanying each report. Look for instance at those figures of 27 cases of "Cardiac" for Pfizer or 30 cases of "Blindness" for AZ. That is not acceptable data to a clinical scientist because during clinical trials and during post-marking surveillance they don't like to deal in symptoms they want to know the underlying condition (they record the symptoms as well of course). That's why there is often quite a lot of follow up work to determine for instance what the actual conditions where that gave rise to those 37 reports of "blindness" - retinal detachments? various macula conditions? cataracts? etc, etc.

And then in the UK it gets even worse because a few years ago we (the UK) opened up the yellow card reporting system so that the general public can file reports and my friend says that many of those verge on the equivalent of crank calls. Funnily enough just the day after our conversation on this a few newspapers ran an article on the weirdest side effects of the AZ vaccine which include teeth growing back (lucky for Lootman that he got the Pfizer jab!), diet plans stopping working and there was even one report of the AZ vaccine causing "retirement" (be careful those of you early in your careers, you might want to make sure you avoid the AZ vaccine). I would be pretty sure that those side effect reports came in via the public reporting channel.

I honestly think it's worth bearing the above in mind when looking at these Yellow Card totals. The death data will be accurate because I am sure every death is followed up with great urgency to validate and assign a diagnosis ("death" is obviously just a symptom not a diagnosis) but who knows how much of the rest is good quality data vs potentially much less reliable public reporting. It makes me wonder whether, with all the twitchiness and bad press around the AZ vaccine, whether the public channel might be getting far more AZ Yellow Card reports than Pfizer yellow card reports since a certain percentage of AZ recipients are now much more sensitised to possible side effects. Essentially AZ might be seeing a stronger nocebo effect than the Pfizer vaccine is and the public Yellow Card system is the ideal channel through which to get maximum exposure to any nocebo effects.

- Julian

...Maybe yet still a bit early, but so far I can say the only side effects I have experienced from two AstraZeneca vaccinations is very slight soreness at the vaccine site in the arm, when pressed upon.

Oh boy, here we go again! We talk about first wave, second wave, third wave wrt the virus but we seem to be having multiple waves of bad news re various countries' governmental reactions to the AZ vaccine. Here's the latest wave of bad news and I've lost count of what wave this might count as now!...

Canada suspends use of AstraZeneca Covid vaccine for those under 55
Canada on Monday suspended the use of the Oxford/AstraZeneca coronavirus vaccine for people under 55 following concerns it might be linked to rare blood clots.
...

[ Source: https://www.theguardian.com/world/2021/ ... e-under-55 ]

and also from the Guardian live blog today ...

Berlin state hospitals halt AstraZeneca vaccinations of women under 55
Berlin’s state hospital groups Charite and Vivantes have stopped giving women under 55 shots of AstraZeneca’s Covid vaccine, a spokeswomen for the hospitals confirmed.

The moves follow reports of rare but serious blood clots, bleeding and in some cases death after vaccination, mainly in young women.
...

Source: This is a link to the live blog. If this doesn't go to the specific entry (it does for me) then the entry was posted at 11:10 today - https://www.theguardian.com/world/live/ ... d2736593f0 ]

- Julian

And now Canada has followed suit. Great. My daughter is just 52 and thought she had better have the AZN jab as they wouldn't give her the Pfizer.
Incidentally, my daughter is pretty sure she and her husband and son all had the virus last year though they didn't get tested. One wonders why it is mostly women under 55 who are affected by blood clots in the brain and now excluded from vaccine administration. What is magical about 55? Could it be that they are more likely to have had the virus and were effectively getting a booster dose, possibly too close to their infection? I think in my daughter's case IIRC it was quite early last year.

Suspending the use of an available AZN vaccine might mean that folk are having to wait to get vaccinated. I'm keeping a watch on cases and deaths in Euroland. Are the concerns genuine or political posturing?

Bouleversee wrote:One wonders why it is mostly women under 55 who are affected by blood clots in the brain and now excluded from vaccine administration. What is magical about 55?

I don't know but a friend of my wife just had a "mini" stroke due to a blood clot in the brain, and now she has to have a full body scan to see if there are more. She is 53.

Hasn't had Covid as far as we know. No vaccine yet.

Is that here or in the US?

Bouleversee wrote:Is that here or in the US?

She is in California.

Thanks, Lootman. That rather endorses the claims that post vaccine clotting/bleeding cases are no more numerous than they are without any Covid context.

monabri wrote:Suspending the use of an available AZN vaccine might mean that folk are having to wait to get vaccinated. I'm keeping a watch on cases and deaths in Euroland. Are the concerns genuine or political posturing?

Given the low rates of vaccination in Canada and the EU there will be no shortage of over 55 candidates for vaccine. While it can clearly be of concern to individuals, In the short term (a couple of weeks) suspending shots for the under 55 should have no effect on vaccine rollout.

Limiting shots for under 55s might even be desirable from the point of view of vaccinating the most vulnerable first. It is even possible that this is leaking through to the decision to limit shots to over 55, at least to the extent that some people are not pushing back as hard as they might. In the long term, casting unnecessary shade on any of the vaccines will be bad, but not as bad as not casting necessary shade.

Damn that EU, they've really got it in for us!

AstraZeneca COVID-19 vaccine: review of very rare cases of unusual blood clots continues Share
News 31/03/2021

https://www.ema.europa.eu/en/news/astrazeneca-covid-19-vaccine-review-very-rare-cases-unusual-blood-clots-continues

"At present the review has not identified any specific risk factors, such as age, gender or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven, but is possible and further analysis is continuing.

As communicated on 18 March, EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalisation and death, outweigh the risks of side effects."

Back on Jan 20, I reported my first jab - all very efficient etc.

About 5 days ago I received text please turn up on Thursday 1 April etc.

Again all very efficient. Wonderful bunch of volunteers helping out.

When I got home, someone mentioned 2 jabs T7 - I gave them a left hook,

T7

I see in the rolling 7 day average for the vaccine that second doses have now overtaken first doses.

https://www.bbc.co.uk/news/uk-56626313