The biology of coronavirus COVID-19 - including research and treatments

But I'm not entirely sure the efficacy figure is the only valid metric, which I think only identifies those who do not develop symptoms.

In my post https://www.s4me.info/threads/the-b...vaccines-treatments.14022/page-57#post-314306 there is a link that @Snow Leopard provided, and it seems to be saying that even though more people develop symptoms with the Oxford vaccine, not a single person on the trial who was administered two doses became hospitalised. Now I appreciate that this also is not the only metric of interest, but I would be far happier having this vaccine if I knew it reduced my symptoms from death to not needing hospital.

ETA: I realise @Trish also made this point in her post https://www.s4me.info/threads/the-b...vaccines-treatments.14022/page-58#post-314321.
 
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If people get vaccinated with the Oxford vaccine and it turns out to not be effective enough, can they then get vaccinated with the Pfizer one too?

What is "not effective enough"?
In my post #1137 above there is a link that @Snow Leopard provided, and it seems to be saying that even though more people develop symptoms with the Oxford vaccine, not a single person on the trial who was administered two doses became hospitalised.
How do I find post #1137?
Can you link again?
The question i would have is how many in the placebo group were hospitalised.
 
But I'm not entirely sure the efficacy figure is the only valid metric, which I think only identifies those who do not develop symptoms.

In my post #1137 above there is a link that @Snow Leopard provided, and it seems to be saying that even though more people develop symptoms with the Oxford vaccine, not a single person on the trial who was administered two doses became hospitalised. Now I appreciate that this also is not the only metric of interest, but I would be far happier having this vaccine if I knew it reduced my symptoms from death to not needing hospital.

ETA: I realise @Trish also made this point in her post #1143.

I haven’t been able to follow all the posts, but was the sample of people they used which showed this - that they didn’t need hospitalisation - large? And did it include people who are more vulnerable to COVID, and more likely to be hospitalised or die? Because I thought I read somewhere that this vaccine wasn’t tested on certain groups of people? And what about the placebo group - how many of them were hospitalised / died?

Edit: cross posted with @BurnA who asked the same question!
 
I haven’t been able to follow all the posts, but was the sample of people they used which showed this - that they didn’t need hospitalisation - large? And did it include people who are more vulnerable to COVID, and more likely to be hospitalised or die? Because I thought I read somewhere that this vaccine wasn’t tested on certain groups of people? And what about the placebo group - how many of them were hospitalised / died?

Edit: cross posted with @BurnA who asked the same question!
Valid points. Age range 18–55, so not so vulnerable so far as age concerned. Will look further.

ETA:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32623-4/fulltext
No COVID-19-related hospital admissions occurred in ChAdOx1 nCoV-19 recipients, whereas ten (two of which were severe) occurred in the control groups.
 
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@Barry

Hmm that seems like a small number in the control group as well. Would that even be statistically significant? I’ve honestly forgotten everything I ever learned in maths & stats.

I’m just scrolling through the link you gave and haven’t found the sample size - but they do say this:

“The limitations include that less than 4% of participants were older than 70 years of age, no participants older than 55 years of age received the mixed-dose regimen, and those with comorbidities were a minority, with results for that subgroup not yet available. ”

So I don’t really know if we can draw the conclusion it’s effective in reducing deaths and hospitalisations? Especially in the vulnerable population & co morbidities which is what it needs to reduce it in the most? And possibly by a small amount (given the control group findings), if anything (if that’s even statistically significant)? Am I missing something? I’m not able to read the whole paper.
 
But I'm not entirely sure the efficacy figure is the only valid metric, which I think only identifies those who do not develop symptoms.

In my post https://www.s4me.info/threads/the-b...vaccines-treatments.14022/page-57#post-314306 there is a link that @Snow Leopard provided, and it seems to be saying that even though more people develop symptoms with the Oxford vaccine, not a single person on the trial who was administered two doses became hospitalised. Now I appreciate that this also is not the only metric of interest, but I would be far happier having this vaccine if I knew it reduced my symptoms from death to not needing hospital.

ETA: I realise @Trish also made this point in her post https://www.s4me.info/threads/the-b...vaccines-treatments.14022/page-58#post-314321.
Was this trial not stopped twice due to significant adverse events ( Guille barre?)
 
So i was attempting to explain to my carer today that the AZ vaccine had much lower efficacy than Pfizer.... she didnt believe me said 'it cant be they wouldnt have authorised it'
<sigh>
i said i would get proof....
i looked on your link @Snow Leopard but i couldnt make it out, sorry to be so dense - I looked at the table but i cant see where it says 53%
If you have time could you point out to me where it says it so i cant point it out to her.

It is in the table "COVID-19 Vaccine AstraZeneca efficacy against COVID-19" on the right hand side, in the row starting with "COVID-19 cases after dose 1":
The actual number is 52.69 with 95% CI of (40.52, 62.37)

For two doses the figure is 70.42 CI: (58.84, 80.63), but for some strange reason they've used a 95.84% CI.
Also, the analysis seems to be based on the interim phase 3 data (that was published in the Lancet on Dec 8) combined with the phase 1/2 data. As such, the reported data is only for 5,807 of the 12,021 randomised participants that have received at least one dose of the vaccine.

I am also confused because i thought the better efficacy was from giving a 1/2 dose & then a full dose later - something that was discovered through some kind of error/serendipitous event... but the MHRA have authorised 2 full doses....
eh??? that doesnt seem to make sense what am i missing.

That is what they claimed based on cherrypicking the data the first time. The problem is they don't have enough data to confirm that the LD/SD combination actually works better, so they weren't able to get approval for this.

If people get vaccinated with the Oxford vaccine and it turns out to not be effective enough, can they then get vaccinated with the Pfizer one too?

Yes, but we don't know how this will affect the overall efficacy.

I speculate that if people are going to be re-vaccinated with the Pfizer (or another alternative with similar effiacy) it will be a while down the track, like 12+ months

So wait. This is giving me a headache.

[...]

This is really stressing me out.

All valid questions. It looks confusing because it is!

But I'm not entirely sure the efficacy figure is the only valid metric, which I think only identifies those who do not develop symptoms.

The efficacy against asymptomatic infection for the standard dosage (SD/SD) of the AstraZeneca vaccine was 3.8%, as published in the Lancet. (Table 2)
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl2&pii=S0140-6736(20)32661-1

The question i would have is how many in the placebo group were hospitalised.

The data is in Table 5:
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl5&pii=S0140-6736(20)32661-1

There was one severe COVID-19 case (was in the control group).

Was this trial not stopped twice due to significant adverse events ( Guille barre?)

This is what was stated in the Lancet manuscript:

A case of transverse myelitis was reported 14 days after ChAdOx1 nCoV-19 booster vaccination as being possibly related to vaccination, with the independent neurological committee considering the most likely diagnosis to be of an idiopathic, short segment, spinal cord demyelination.

There were two additional cases of transverse myelitis that were originally reported as potentially related but later determined to be unlikely to be related to vaccination by an independent committee of neurological experts. One case that occurred 10 days after a first vaccination with ChAdOx1 nCoV-19 was initially assessed as possibly related, but later considered unlikely to be related by the site investigator when further investigation revealed pre-existing, but previously unrecognised, multiple sclerosis. The second case was reported 68 days after MenACWY vaccination. While considered possibly related by the site investigator at the time of reporting, an independent panel of neurological experts considered this to be unlikely. All trial participants have recovered, or are in a stable or improving condition.
 
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@Snow Leopard thanks, I have some more questions:

(1) are they going to continue using the rest of the Pfizer vaccine doses that the UK ordered from Pfizer?

(2) You said that you suspect that if they end up re-vaccinating with a more effective one, it won't be until 12+ months down the line. Is that just because the UK didnt initially order enough doses of the Pfizer one?
 
It is in the table "COVID-19 Vaccine AstraZeneca efficacy against COVID-19" on the right hand side, in the row starting with "COVID-19 cases after dose 1":
The actual number is 52.69 with 95% CI of (40.52, 62.37)

For two doses the figure is 70.42 CI: (58.84, 80.63), but for some strange reason they've used a 95.84% CI.
Also, the analysis seems to be based on the interim phase 3 data (that was published in the Lancet on Dec 8) combined with the phase 1/2 data. As such, the reported data is only for 5,807 of the 12,021 randomised participants that have received at least one dose of the vaccine.



That is what they claimed based on cherrypicking the data the first time. The problem is they don't have enough data to confirm that the LD/SD combination actually works better, so they weren't able to get approval for this.



Yes, but we don't know how this will affect the overall efficacy.

I speculate that if people are going to be re-vaccinated with the Pfizer (or another alternative with similar effiacy) it will be a while down the track, like 12+ months



All valid questions. It looks confusing because it is!



The efficacy against asymptomatic infection for the standard dosage (SD/SD) of the AstraZeneca vaccine was 3.8%, as published in the Lancet. (Table 2)
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl2&pii=S0140-6736(20)32661-1



The data is in Table 5:
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl5&pii=S0140-6736(20)32661-1

There was one severe COVID-19 case (was in the control group).



This is what was stated in the Lancet manuscript:
Do we know if severe COVID case was in UK or Brazil?
Higher viral loads and different control compound in Brazil provide slightly different picture ?

ETA- seems to be hospitalised adverse reaction(s) in India too
 
I may be off base but my understanding is that vaccine effectiveness is in addition to the baseline risk a person has without any vaccine. For example if someone is considered to have a 99% chance of surviving Covid-19 and they get a vaccine that is 90% effective then they now have a 99.9% chance of surviving. Leaving just a 0.1% chance of death.
 
I may be off base but my understanding is that vaccine effectiveness is in addition to the baseline risk a person has without any vaccine. For example if someone is considered to have a 99% chance of surviving Covid-19 and they get a vaccine that is 90% effective then they now have a 99.9% chance of surviving. Leaving just a 0.1% chance of death.

That is the likely situation but it is not certain. If 90% effectiveness is defined in terms of blocking clinical symptoms then the effectiveness in preventing death may be greater roles than that.

Your person considered to have a 99% chance surviving is effectively one of a population of 1000 that cannot be told apart amongst which there are only ten who would die if exposed to the virus, for reasons we do not know. Give them all the vaccine and only 100 will get symptoms of Covid. But the ones who were going to die might still all die because they have some defect in being able to mount an adequate immune response.

On the other hand it might work the other way. Just a bit of immunity from vaccine might stop everyone dying.
 
The latest I have heard, on Radio 4 this morning, is that the difference in efficacy for the half dose group is now being attributed to the group who had the small dose also being part of a larger group who had a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity better.

They are also reiterating that the efficacy of the different vaccines can't be compared directly, as the trials were carried out differently, and different things were measured.

I think the roll out of whatever vaccine is available and approved is largely because of the very high and rising infection, hospitalization and death rates in the uk at the moment. Anything that has a chance of helping reduce that is regarded as medically helpful.
 
@Snow Leopard thanks, I have some more questions:

(1) are they going to continue using the rest of the Pfizer vaccine doses that the UK ordered from Pfizer?

(2) You said that you suspect that if they end up re-vaccinating with a more effective one, it won't be until 12+ months down the line. Is that just because the UK didnt initially order enough doses of the Pfizer one?

Yes, I assume that they will continue using the Pfizer vaccine i.e. (as you indicate) the amount they've contracted to buy - same for Moderna. Combined enough to vaccinate 25 million people in the UK?

I assume that if you get the Pfizer/Moderna vaccine then you'll get 2 doses of it --- interesting that they are now looking at widening the gap between first and second (booster) doses.

I have no more knowledge than you though!

I assume this is all down to shortage of RNA vaccine capacity* --- here's hoping AstraZenica works:emoji_fingers_crossed:

EDIT - Bill Gates mention low capacity to make RNA vaccines here in BBC Radio 4 - How to Vaccinate the World https://www.bbc.co.uk/sounds/play/m000qnbz
 
Yes, I assume that they will continue using the Pfizer vaccine
They are still going to use the Pfizer vaccine. From 4th January people with appointments to have their second dose will have that appointment cancelled and will be given one with a 3 month interval instead. The reasons given are that the longer interval (may) increase the boosting effect of the second dose, and that it means they can give more people a first dose sooner, which they say provides pretty good immunity after 3 weeks even without the second dose. I assume it will continue to go to centres such as hospitals which have appropriate freezing facilities.
 
They are still going to use the Pfizer vaccine. From 4th January people with appointments to have their second dose will have that appointment cancelled and will be given one with a 3 month interval instead. The reasons given are that the longer interval (may) increase the boosting effect of the second dose, and that it means they can give more people a first dose sooner, which they say provides pretty good immunity after 3 weeks even without the second dose. I assume it will continue to go to centres such as hospitals which have appropriate freezing facilities.

Yes the key constraint, for the Pfizer (-70) vaccine but not Moderna (-20), is access to minus 70 freezers i.e. for longer term storage.

Has anyone quantified "pretty good immunity --- without the second dose"?

@Snow Leopard
 
The latest I have heard, on Radio 4 this morning, is that the difference in efficacy for the half dose group is now being attributed to the group who had the small dose also being part of a larger group who had a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity better.

They are also reiterating that the efficacy of the different vaccines can't be compared directly, as the trials were carried out differently, and different things were measured.

I think the roll out of whatever vaccine is available and approved is largely because of the very high and rising infection, hospitalization and death rates in the uk at the moment. Anything that has a chance of helping reduce that is regarded as medically helpful.

Interesting that the consider that "a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity".

Also I'd agree that "I think the roll out of whatever vaccine is available and approved is largely because of the very high and rising infection" I'm not sure if we see the consideration behind the approval. I think it's also correct; the Independent Sage statement is pretty stark https://www.independentsage.org/29t...ent-and-call-for-immediate-national-lockdown/
 
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