Developing the Covid-19 vaccine

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Re: Developing the Covid-19 vaccine

Post by shpalman » Tue Feb 02, 2021 6:13 pm

lpm wrote:
Tue Feb 02, 2021 5:36 pm
Oxford University analysis of Oxford-AZ:

(1) 1st dose gives "sustained protection" of 76% during the 3-month interval until the second dose.
Interesting how giving the second dose reduced that to about 60% then.
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Re: Developing the Covid-19 vaccine

Post by lpm » Tue Feb 02, 2021 6:19 pm

They now calculate 82%
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Re: Developing the Covid-19 vaccine

Post by lpm » Tue Feb 02, 2021 6:25 pm

Why are you always so negative?

It's 82% against symptomatic disease. It's close to 100% effective against death, similar against hospitalisation.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Tue Feb 02, 2021 6:28 pm

Are those numbers in a tweet to a paywalled article about a press release?

AIFA still only recommends it for 18-55 year olds.
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Re: Developing the Covid-19 vaccine

Post by lpm » Tue Feb 02, 2021 6:36 pm

So mistrustful.

You foreigners can dither while we Brits save tens of thousands of lives with our Great Patriotic Vaccine.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Tue Feb 02, 2021 6:37 pm

Don't want it anyway.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Tue Feb 02, 2021 7:10 pm

ox-new-Tab2.png
ox-new-Tab2.png (165.88 KiB) Viewed 2259 times
From https://papers.ssrn.com/sol3/papers.cfm ... id=3777268

Their Table 1 doesn't contradict the already-published results on the SD/SD and LD/SD regime.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Tue Feb 02, 2021 7:53 pm

lpm wrote:
Tue Feb 02, 2021 5:36 pm
Oxford University analysis of Oxford-AZ:

(1) 1st dose gives "sustained protection" of 76% during the 3-month interval until the second dose. Does not fall under the UK approach during the 21 day to 12 week extension.

"Data supports the 4-12 week prime-boost dosing interval recommended by many global regulators".

(2) Vaccine stops transmission. "Analyses of PCR positive swabs in UK population suggests vaccine may have substantial effect on transmission of the virus with 67% reduction in positive swabs among those vaccinated".

Pretty great news x2.
That "67% reduction in positive swabs among those vaccinated" is what they get when they pool all the data in that Table 2, so it's mainly based on the 88 symptomatic cases not the 24 asymptomatic cases.

Here's the bit of Table 1 which shows the efficacy against asymptomatic infection from the SD/SD regime as a function of time between the two doses.
ox-new-Tab1-asymp.png
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Re: Developing the Covid-19 vaccine

Post by Bird on a Fire » Wed Feb 03, 2021 12:49 am

So it makes you more likely to get asymptomatic infections? This is like when the military introduced helmets for soldiers and found an increase in head injuries, innit.

What I really don't understand is why after a couple of months you stop getting asymptomatic infections and start getting Japanese currency.
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Re: Developing the Covid-19 vaccine

Post by jdc » Wed Feb 03, 2021 7:45 pm

shpalman wrote:
Tue Feb 02, 2021 6:37 pm
Don't want it anyway.
I'll add you to the list. So far, I've got Shpalman, Belgium, France, Germany, Poland and Italy.

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Re: Developing the Covid-19 vaccine

Post by shpalman » Wed Feb 03, 2021 7:50 pm

Bird on a Fire wrote:
Wed Feb 03, 2021 12:49 am
So it makes you more likely to get asymptomatic infections? This is like when the military introduced helmets for soldiers and found an increase in head injuries, innit.

What I really don't understand is why after a couple of months you stop getting asymptomatic infections and start getting Japanese currency.
Either they ran out of footnote symbols or they screwed up the character mapping when making the pdf.

"¥ Calculated from an unadjusted robust Poisson model."
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Re: Developing the Covid-19 vaccine

Post by shpalman » Wed Feb 03, 2021 8:39 pm

jdc wrote:
Wed Feb 03, 2021 7:45 pm
shpalman wrote:
Tue Feb 02, 2021 6:37 pm
Don't want it anyway.
I'll add you to the list. So far, I've got Shpalman, Belgium, France, Germany, Poland and Italy.
Switzerland isn't convinced yet either.

Well, this is mainly about ages >55-65 and I hope I'll be vaccinated before I arrive in that group.

But it's moot if AstraZeneca doesn't have any vaccines to deliver in continental Europe, and the EU is a long way from having even the >80's done (or has barely started) with Pfizer or Moderna doses.

Rollouts might have to be reorganized if the AZ one starts being available in large quantities very soon but national regulators still don't recommend it for the >55's.
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Re: Developing the Covid-19 vaccine

Post by jdc » Wed Feb 03, 2021 10:44 pm


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Re: Developing the Covid-19 vaccine

Post by Herainestold » Thu Feb 04, 2021 12:48 am

jdc wrote:
Wed Feb 03, 2021 7:45 pm
shpalman wrote:
Tue Feb 02, 2021 6:37 pm
Don't want it anyway.
I'll add you to the list. So far, I've got Shpalman, Belgium, France, Germany, Poland and Italy.
I don't want it either. I want Pfizer or Moderna. But I will take whatever I get. Except Can Sino.
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Re: Developing the Covid-19 vaccine

Post by Woodchopper » Thu Feb 04, 2021 5:30 pm

Oxford AstraZeneca Data, Again

[...]

This new preprint reports on 1293 participants who had a 12-week interval between two standard doses. Efficacy in this group was 82.4% (95% CI of 62.7% to 91.7%), which would seem to be a notable improvement. That’s not a very large sample, and the confidence intervals between the four-week and the twelve-week group still overlap in the 60% efficacy range, but you can make a case (and AstraZeneca certainly is) that this shows better overall effects.

Another key piece of data is the efficacy seen during that 12-week period: 76% (95% CI of 59% to 86%), which is basically the same as when analyzed after the second dose. The preprint makes the point (and I agree with them) that the second dose is likely to be needed for longer-lasting protection, because it really does raise antibody titers significantly, but it certainly looks like the protection from a single dose with a longer delay is worthwhile, and that the delay will not hurt things (and may well make the overall efficacy higher).

Why should this be? The answer is “immunology”, and that’s not just the last refuge of scoundrels. Historically, it appears that longer delays in a two-dose regime can make things better, make them worse, or not make much difference, and the only way to be sure is to go out and get the clinical data. So even though this is not a large 12-week data set, I’m glad to see it. I think that the UK’s move to get as many first doses into the population as they can was the right one, and it’s good to see some data that at least don’t undermine it.

What about the low-dose/standard dose business, though? This preprint offers a possible explanation: it turns out that the cohort that got the lower dose at first also had a longer delay before getting the second dose. So it’s possible that the apparent increase in efficacy was driven less by the lower first dose than by the longer gap between the doses. We can’t rule out an effect from both, though – the data are just not in a shape to do that. Overall, the complaints that I (and many others!) have had about the data collection and rollout for this vaccine are still valid: we’re learning what could be important things about this candidate from analysis of small subgroups, some of which were themselves the results of mistakes and miscommunication during the trials. And the release of that data has been just as patchy and noisy – you really would have expected better from AstraZeneca.

But there is something good to say about their data collection: since the UK study that’s included in these numbers tested its subjects by nasal swab every week, regardless of any symptoms, we can actually get a read on something that everyone’s been wondering about: transmission. It’s become clear from all the successful trials that vaccination (whether by mRNA, the several different viral vectors, or recombinant protein) is extremely effective at keeping people out of the hospital and at preventing people from dying from the coronavirus. This is very good news, and it deserves to be highlighted. But are those severe cases just being converted to lesser ones, with other lesser cases then being converted to asymptomatic ones, and in that case has the number of people walking around shedding infectious virus really changed?

The swab data say that it has. It appears that the vaccine reduced the number of people showing PCR positivity by 50 to 70%. The actual numbers were -67% after the first dose and -54% overall, but I wouldn’t read anything into that difference, because the confidence intervals for those two measurements completely overlap. So it looks like everything is shifted: hospitalized cases end up being able to stay at home with more moderate symptoms, people who would have had moderate symptoms end up asymptomatic, and people who would have been asymptomatic end up not testing positive at all. Oh, and people who would have died stayed alive. There’s that, too.
https://blogs.sciencemag.org/pipeline/a ... data-again

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Re: Developing the Covid-19 vaccine

Post by shpalman » Thu Feb 04, 2021 6:41 pm

The next bit says:
If you just look at efficacy in preventing asymptomatic infection, you get a really low number (16% efficacy, confidence interval banging into the zero baseline). But my interpretation of that is that the overall number of asymptomatic patients didn’t change too much, because as just mentioned, the “would have been asymptomatic” group is not showing infection at all, and their numbers have been replaced by people from the “would have been showing symptoms” cohort, who are now just asymptomatic.
So it doesn't really reduce the number of asymptomatic carriers wandering around. There were 13 asymptomatic cases in the control group vs. 71 symptomatic cases, and if they're representative of the general population then there just aren't loads of asymptomatic carriers wandering around anyway (or at least, asymptomatic but with a high enough viral load to show up in PCR and presumably also infect someone else) so it's not a massive problem which needs solving.

Symptomatic carriers shouldn't be a problem for spread anymore because people with symptoms should self-isolate and other people should stay away from them whether or not the symptoms are confirmed to be from covid.

It's great that they did regular swabbing of all the trial participants, and the vaccine does work to stop people getting ill and dying, but it's not entirely justified in my opinion that they are using this figure of 67% (which is "Any PCR+ 22-90 days") to say that it reduces transmission, in anything but the obvious way in which all the vaccines do.
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Re: Developing the Covid-19 vaccine

Post by Millennie Al » Fri Feb 05, 2021 3:18 am

shpalman wrote:
Thu Feb 04, 2021 6:41 pm
There were 13 asymptomatic cases in the control group vs. 71 symptomatic cases, and if they're representative of the general population then there just aren't loads of asymptomatic carriers wandering around anyway (or at least, asymptomatic but with a high enough viral load to show up in PCR and presumably also infect someone else) so it's not a massive problem which needs solving.
When I checked the figures as these studies were first appearing, I remember I found that participants were very much not representative of the general population - they were far less likely to be infected even in the control group. This is why the studies took much longer than originally expected - the expectation was based on the prevalence in the general population, but the studies just didn't have enough people getting infected.
Symptomatic carriers shouldn't be a problem for spread anymore because people with symptoms should self-isolate and other people should stay away from them whether or not the symptoms are confirmed to be from covid.
However, sympomatic carriers seem to start out as asymptomatic carriers and show symptoms after having been infectious.

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Re: Developing the Covid-19 vaccine

Post by shpalman » Fri Feb 05, 2021 7:41 am

Millennie Al wrote:
Fri Feb 05, 2021 3:18 am
shpalman wrote:
Thu Feb 04, 2021 6:41 pm
There were 13 asymptomatic cases in the control group vs. 71 symptomatic cases, and if they're representative of the general population then there just aren't loads of asymptomatic carriers wandering around anyway (or at least, asymptomatic but with a high enough viral load to show up in PCR and presumably also infect someone else) so it's not a massive problem which needs solving.
When I checked the figures as these studies were first appearing, I remember I found that participants were very much not representative of the general population - they were far less likely to be infected even in the control group. This is why the studies took much longer than originally expected - the expectation was based on the prevalence in the general population, but the studies just didn't have enough people getting infected.
Symptomatic carriers shouldn't be a problem for spread anymore because people with symptoms should self-isolate and other people should stay away from them whether or not the symptoms are confirmed to be from covid.
However, sympomatic carriers seem to start out as asymptomatic carriers and show symptoms after having been infectious.
Well, yes, but all the (working) vaccines stop there being so many symptomatic carriers who presumably started out as asymptomatic carriers, so this isn't an argument for the AstraZeneca one in particular leading to lower transmission.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Fri Feb 05, 2021 8:28 pm

Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
Efficacy of ChAdOx1 nCoV-19 against the B.1.1.7 variant of SARS-CoV-2 is similar to the efficacy of the vaccine against other lineages. Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease.
written up at https://www.theguardian.com/world/2021/ ... ls-suggest
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Re: Developing the Covid-19 vaccine

Post by Martin Y » Fri Feb 05, 2021 9:00 pm

shpalman wrote:
Fri Feb 05, 2021 8:28 pm
Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
Efficacy of ChAdOx1 nCoV-19 ...
Is it just me who now has a kneejerk response to alternating upper and lower case characters and had to re-read several times to be sure that a mocking tone was not implied?

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Re: Developing the Covid-19 vaccine

Post by shpalman » Fri Feb 05, 2021 9:17 pm

Especially as it's me posting about it.

I notice that the writeup says "the scientists reported that levels of neutralising antibodies – those that wipe out the virus – were nine times lower in vaccinated people who caught the Kent variant, named B117, compared with those who contracted older variants.

But the reduced antibody response was associated with only slightly lower protection against symptomatic infections with the Kent variant, the scientists said."

Because to defend their vaccine against the idea that it doesn't work in older people (it might work, we just don't have much efficacy data) they point out that the antibody responses are the same.
Further analysis revealed that those who received the Oxford jab but still became infected shed the virus for a shorter time and had lower viral loads than those in the control group. The findings may help to explain why the vaccine appears to reduce transmission by as much as two-thirds after the first shot.
Where's this data which says that it "appears to reduce transmission by as much as two-thirds"? There's only that line in that table which says that efficacy is 67% if you include all PCR positives, both symptomatic and asymptomatic, between 22 and 90 days after the first dose.
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Re: Developing the Covid-19 vaccine

Post by Woodchopper » Sat Feb 06, 2021 8:08 pm

Man makes a Covid vaccine himself (with help from a biotech company and plans he found on teh interwebs)
https://www.lesswrong.com/posts/niQ3heW ... ng-vaccine

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Re: Developing the Covid-19 vaccine

Post by shpalman » Mon Feb 08, 2021 10:47 am

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Re: Developing the Covid-19 vaccine

Post by shpalman » Mon Feb 08, 2021 11:55 am

The WHO are going to meet to discuss the AstraZeneca vaccine
The 1.5m AstraZeneca vaccines obtained by South Africa, which will expire in April, will be kept until scientists give clear indications on their use, he added.
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Re: Developing the Covid-19 vaccine

Post by shpalman » Mon Feb 08, 2021 3:14 pm

Before you compare the Covid vaccines, here are five ways in which we can distract you about how disappointing the Oxford one is
1. Vaccines and the diseases they prevent are all different
Don't know why everyone's obsessed with this "covid-19" thing at the moment.
2. Vaccines don’t guarantee complete protection
In a pandemic you need results fast, so all the studies are measuring prevention of relatively mild but more common cases in order to get the numbers quickly.
In a pandemic you also get the numbers quickly, and if the relatively mild cases are more common, then, well, good.
So, if you receive a vaccine that is reported to be, say, 80% efficacious against symptomatic disease,
For example, not the AstraZeneca one
your chance of getting really seriously ill should go down by more than 80%, possibly close to 100%, although no vaccine ever hits 100% guaranteed protection against anything.
because vaccines don’t guarantee complete protection, so you won't get 100%, but you might get 100%, except you won't get 100%, but you might. But you won't.
3. You can’t compare the numbers from different trials
Each trial will involve different people in different places
For example, the Pfizer one has been tested in Brazil while the AstraZeneca one has been tested in also Brazil.
4. You can’t compare the results of randomised trials with the results of ‘real-world’ studies
Trials use mostly young healthy people, less prone to fall ill for different reasons, making the trials run more smoothly and quickly
for example, the Pfizer one only had 15,921 subjects over 55 years old out of a total of 37,706, so their excellent efficacy in that age group is obviously meaningless as compared to the Oxford one; better to look at the real world data, for example in Israel in which cases and hospitalizations are coming down in the vaccinated age group as opposed the UK in which they aren't.
5. Most (but not all) vaccines reduce transmission, to create ‘herd immunity’
... but we've no idea if these ones do.

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