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Fragile Bird

Covid-19 #25: The Prisoner’s Dilemma

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1 hour ago, Altherion said:

Their population is about 100K people so yes, it's a lot easier, but it's still curious because they had to have imported the vaccine from somewhere.

India gave them for free according to this article.

Quote

 India is sending doses free of charge to Nepal, Bangladesh, Myanmar, the Maldives, Sri Lanka, the Seychelles and Afghanistan. India's foreign minister calls this "Acting East. Acting fast."

https://www.dw.com/en/opinion-western-democracies-must-address-vaccine-inequity-whatever-it-takes/a-56652813

 

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17 hours ago, Heartofice said:

Clearly that is the case in countries like Germany where much of the bad press, led by politicians, has led to many AZ vaccines being left on the shelf.

There was bad press, but not led by politicians. The politicians are trying all the time to improve vaccination compliance here.

I think we also found a good solution for the AZ vaccine now . we are still vaccinating in priority group one (over 80, care home residents,  and people working in hospitals and care homes). since AZ couldnt be used for the over 80 it was only offered to these professions. BUT already 1,4 mio of these people had the first jab of the biontech vaccine, so need a second biontech as well. that left not so many people and some of them were more unsure about AZ.

Now, while we continue to give moderna and biontech only in priorty group one to the over 80, we open AZ for priority group two: thats over 70 (which cant get AZ) and people with certain illnesses,  then certain professions like family doctors and also -after long discussion- teachers. Thats really a lot of people and there will be not problem to find enough people to take the vaccine.

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On 2/21/2021 at 1:12 PM, ljkeane said:

They aren't comparing the same thing. It's comparing the efficacy between 22 and 90 days of a single dose to the overall efficacy of two doses with less than a six week gap. If the overall efficacy of a single dose was higher than two doses then that would raise some questions about but that's not what it's saying.

Vaccine efficacy was defined in the same way for the single dose and two doses, so I don't see why you couldn't compare the efficacy between the different dosing regimes.  Since you mentioned that the preprint paper that you cited has undergone peer review and publication as a regular paper, I looked it up to see if anything was different. One of the few changes beyond minor edits was the insertion of the following paragraph, which acknowledges the counterintuitive result of the single dose having a higher efficacy than the double dose:

Quote

The slightly lower vaccine efficacy against symptomatic COVID-19 of 66·7% after a booster dose appears counterintuitive compared with the 76% efficacy after a single dose, although these differences are non-significant. Cases included in single-dose estimates occurred earlier in the year than those included in post-second-dose analyses, and the intensity of the epidemics varied in the different countries, making single-dose and two-dose estimates difficult to directly compare with each other.

A lot of the peer reviewers must have also had the same concerns for the authors to insert this paragraph.  I'm OK with their explanation because their study design and data is frankly a bit messy.  The BBC articles didn't provide the large confidence intervals around the reported data points which would have been a possible explanation for the confusing reported result, and I recall discussing this result as strange with Padraig when it was first reported.

I also noticed when looking over the data from the paper that one of the study groups was in South Africa, but unfortunately, they didn't provide the efficacy numbers from each of the groups.  It would have been interesting to get the efficacy numbers broken down by the country groups, because it's possible that the efficacy numbers were dragged down a bit by the South African variant.  

The data from Scotland has been very encouraging, although it's not from a randomized double blind clinical trial.  Data from a large US study is coming out soon too.  Unfortunately, the US study appears to only have a fixed spacing between the doses of 29 days.  It's possible they changed the study design in the middle of the trial, but that is normally a large red flag and complicates interpretation of the data.  I'm curious to see whether the efficacy numbers will be higher than 60-70% since the South African variant doesn't appear to be common in the US yet.

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29 minutes ago, Mudguard said:

Vaccine efficacy was defined in the same way for the single dose and two doses, so I don't see why you couldn't compare the efficacy between the different dosing regimes.  

Like I said to Pod, you're not comparing single dose efficacy with two dose efficacy though. You're comparing single dose efficacy in a cherry picked window in which it should be at it's most effective with two dose efficacy.

ETA: Also they're just using data from their existing trials so I'd expect a significant proportion of data from South Africa predates the spread of the new variant so I'm not sure how much of a difference it makes.

Edited by ljkeane

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8 minutes ago, ljkeane said:

Like I said to Pod, you're not comparing single dose efficacy with two dose efficacy though. You're comparing single dose efficacy in a cherry picked window in which it should be at it's most effective with two dose efficacy.

ETA: Also they're just using data from their existing trials so I'd expect a significant proportion of data from South Africa predates the spread of the new variant so I'm not sure how much of a difference it makes.

Your explanation still doesn't make sense to me, and it's not mentioned at all as a possible explanation in the peer reviewed paper.  Again, it doesn't make sense for the efficacy to go down after you give the second dose.  If the efficacy of the single dose is 70% for the first 90 days, and then you give the second dose, you would expect that the efficacy goes up, not down. 

The paper's explanation is that the difference isn't statistically significant, i.e., they are more or less the same in terms of efficacy, and that the benefit of the second dose is not increased efficacy but instead protection over a longer duration.  I don't completely buy that rationale, but it's possible and based on their data there's not much else they can say.  My guess is that if the data was cleaner, from a larger and better run trial for example, you would see increased efficacy after the second dose.  Moderna's and Pfizer's vaccines show this trend, which is normally what you would see with all vaccines unless there was a problem with the booster shot.  With the adenovirus based DNA vaccines, especially if the same adenovirus was being used for both shots as in the AstraZeneca vaccine, there was a concern that the patient's immune response would generate anti-adenovirus antibody after the prime shot that would reduce the effectiveness of the booster shot.  I think their way of getting around this was to simply give a very large dose of the vaccine and hope enough got through.

I would have liked to see antibody data that allowed comparison of antibody levels between the single and double shots to confirm that the booster was effective, but for some reason the antibody data from the single shot is presented using a different assay than the double shot, which makes it impossible to compare the antibody levels.  The paper cites data from their phase I/II study as providing evidence that a booster shot increased antibody levels, but that was based on just 10 subjects receiving the booster shot, while over 500 received just a single shot.  No idea why just 10 subjects received the booster, and it seems crazy to me to change the design of the phase III study based on antibody results from just 10 subjects.  Again, very poor planning.  And I think they might have started the phase III trial before the results of the phase I/II trial was completed, otherwise there shouldn't have been a need to change the dosing schedule of the phase III trial after it started.

Regarding the South African variant, an article in the New York Times dated December 19, 2020 claims that at the time 90% of the sequences analyzed in South Africa from new cases came from the new variant.  It must have been spreading for quite some time to become that dominant.  If the efficacy data from South Africa was in line with the other countries, it would be strong evidence that it wasn't prevalent at the time.  On the other hand, if the efficacy from South Africa was lower, that could be explained by the new variant.  I would have liked to see that data.  Maybe it will come out later in a subsequent analysis.  Presumably they will continue to report on the updated data they collect, at least until the control subjects begin to be vaccinated and comparisons can no longer be made.

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2 hours ago, Mudguard said:
  Quote

The slightly lower vaccine efficacy against symptomatic COVID-19 of 66·7% after a booster dose appears counterintuitive compared with the 76% efficacy after a single dose, although these differences are non-significant. Cases included in single-dose estimates occurred earlier in the year than those included in post-second-dose analyses, and the intensity of the epidemics varied in the different countries, making single-dose and two-dose estimates difficult to directly compare with each other.

All very interesting.

9 hours ago, mcbigski said:

Does that mean they're open for tourism?

The answer is yes.  If you are vaccinated. :)

https://edition.cnn.com/travel/article/countries-open-to-vaccinated-travelers/index.html

As well as getting doses from India, it was in response to China sending 50k!  Nice to be in a strategic area.  Or they want to go on holiday themselves!

https://www.wsj.com/articles/covid-19-vaccines-are-becoming-important-diplomatic-currency-11613152854

13 hours ago, Altherion said:

I'm kind of amazed that we had not outsourced all vaccine production yet so there are still places in the US where they can be manufactured, but this does mean that it's more or less the whole 7 billion that are behind the 8-ball, not just a fifth of them. Even the wealthy and technologically advanced EU is significantly lagging.

This is a very interesting topic.  While you'd think the big pharmaceutical companies would be all over the vaccine business, a lot of them aren't.  Historically there wasn't a lot of money to be made in vaccines apparently.  The J&J vaccine is its 1st vaccine, despite it being the biggest pharma company in the world.  Pfizer is massive but Biontech, a much smaller German company, developed the technology.  While this could have given the EU an advantage, Biontech didn't have the scale, so Pfizer got involved, helping the US.  Sanofi, a big French pharmaceutical company are trying to develop a vaccine but they have had major difficulties.  Merck just gave up after trying.  Roche is focusing on testing.  Novartis and Bayer have very recently signed deals to manufacture vaccines for other companies but you'd have preferred if that happened months ago.  (There is a reasonable question why they weren't pushed to do this earlier).

Thus you end up with smaller companies like Astrazeneca (British/Swedish), Moderna (US), Curevac (German), Novavax (US) appearing on the scene but they are having scale issues. 

Anyhow, 60% of the world's vaccines are produced in India but pharma factories are still in many Western countries.  Just not the right kind.  Maybe Europe relied on India even more than the US when it came to vaccines?  And the money in Operation Warp Speed probably benefited the US pharma companies also.

 

Edited by Padraig

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3 minutes ago, Mudguard said:

Your explanation still doesn't make sense to me, and it's not mentioned at all as a possible explanation in the peer reviewed paper.  Again, it doesn't make sense for the efficacy to go down after you give the second dose.  If the efficacy of the single dose is 70% for the first 90 days, and then you give the second dose, you would expect that the efficacy goes up, not down.

The comparison should be two dose efficacy up to 90 days if you really wanted to make a direct comparison. They do just say the difference isn't statistically significant and they don't go into a great deal of detail because they aren't really comparing the two.

There are overlapping confidence intervals so, you're right, it may well be that the overall efficacy of two doses with less than 6 weeks gap is above the 22 to 90 days efficacy of a single dose if that really concerns you. We also don't know what the lifetime of any of these vaccines are and how their effectiveness varies over time. Perhaps the booster dose does increase efficacy over the similar time period then lengthens the duration over which protection tails off. The phase 1/2 trials results you linked to also says what appears to happen is the booster dose increases antibody response but not T-cell response. What influence does that have over the short and long term? As everyone's said it's not a study designed to compare single dose efficacy to two dose efficacy just assuming you can compare short term single dose efficacy with longer term two dose efficacy strikes me as jumping the gun.

1 hour ago, Mudguard said:

Regarding the South African variant, an article in the New York Times dated December 19, 2020 claims that at the time 90% of the sequences analyzed in South Africa from new cases came from the new variant.  It must have been spreading for quite some time to become that dominant. 

The cut off for the data they're using is December 7th. This seems to indicate that the big boost in South African cases was December to mid January. So I'm sure there were some cases of the South African variant it'd be hard to tell how much of an influence it was. I think the problem they have is they've only been able to consistently test for different variants in the UK so far.

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1 hour ago, Padraig said:

As well as getting doses from India, it was in response to China sending 50k!  Nice to be in a strategic area.  Or they want to go on holiday themselves!

https://www.wsj.com/articles/covid-19-vaccines-are-becoming-important-diplomatic-currency-11613152854

Wow. So my suspicions are right. National needs played a big role as geopolitical interests in this export "ban". I wonder if things would have been different had India been a guest in the last virtual G7. Developed countries need to start to become more accommodating to the needs of emerging powers. As we can see, the world needs them.

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I am so mad. So we had this plan that my father would come over and have takeout dinner with us (sister and I) because he misses us or something. (I’m generally a positive person who likes to believe the best, while not ignoring the potential of the worst, and I do think he misses us and there’s no hidden agenda) 

Today his PA had covid symptoms so they went to take an antibody test (not an antigene one, not a PCR, an antibody test). Hers came back positive, his negative. This essentially means, to anybody who has read a single covid article in the past 11 months, that she’s infectious and has been for 4-5 days but her immune system is already responding. While he does not have an immune response to sars-cov-2 as of today. It doesn’t mean he isn’t infected. 

After the tests were done, she put on a mask and went back to the office with him, because.... I suppose she had stuff to pick up? I find it difficult to fathom a reason. 

To me the responsible, sensible and obvious course of action is to send everybody home and get everybody tested AT LEAST for antibody and antigene, if not PCR. And anybody who’s a DIRECT CONTACT of this girl, such as my father, should get a PCR immediately, without delay, and should stay home until their PCR comes back negative. 

I’ll attempt to get my blood pressure back down under 150 and once I succeed, I’ll call him back and postpone this dinner and have a go at convincing him to get a PCR. I just can’t fucking believe why some people thunk they are untouchable and invincible. He is 56 fucking years old and he has hypertension and god knows what else that nobody knows about because he doesn’t believe in medical checkups. Seriously I can’t even... 

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32 minutes ago, RhaenysBee said:

I am so mad. So we had this plan that my father would come over and have takeout dinner with us (sister and I) because he misses us or something. (I’m generally a positive person who likes to believe the best, while not ignoring the potential of the worst, and I do think he misses us and there’s no hidden agenda) 

Today his PA had covid symptoms so they went to take an antibody test (not an antigene one, not a PCR, an antibody test). Hers came back positive, his negative. This essentially means, to anybody who has read a single covid article in the past 11 months, that she’s infectious and has been for 4-5 days but her immune system is already responding. While he does not have an immune response to sars-cov-2 as of today. It doesn’t mean he isn’t infected. 

After the tests were done, she put on a mask and went back to the office with him, because.... I suppose she had stuff to pick up? I find it difficult to fathom a reason. 

To me the responsible, sensible and obvious course of action is to send everybody home and get everybody tested AT LEAST for antibody and antigene, if not PCR. And anybody who’s a DIRECT CONTACT of this girl, such as my father, should get a PCR immediately, without delay, and should stay home until their PCR comes back negative. 

I’ll attempt to get my blood pressure back down under 150 and once I succeed, I’ll call him back and postpone this dinner and have a go at convincing him to get a PCR. I just can’t fucking believe why some people thunk they are untouchable and invincible. He is 56 fucking years old and he has hypertension and god knows what else that nobody knows about because he doesn’t believe in medical checkups. Seriously I can’t even... 

An antibody test just says whether she’s had it and has detectable antibodies. Has nothing to do with infectiousness. She may have had it months ago. 

And her current symptoms could be a re-infection. Or a cold. She should at least get a rapid antigen test.

Edited by Chataya de Fleury

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5 hours ago, Padraig said:

Historically there wasn't a lot of money to be made in vaccines apparently. 

There is a little bit of truth in the old Chris Rock routine, where he notes that the reason we dont have a cure/vaccine for cancer or diabetes, because all the money is to be made in having people come back every month for curing the symptoms. Anyway, vaccines are more one-and-done (or two-and-done), so I imagine in terms of a business model its not as profitable as a drug model. Even though the latter addresses a smaller portion of the entire population, its returns accumulate over time. There may also be money in formulating drugs (for instance, proper release profiles) that may allow for commanding better prices.

Anyway, dont know how India ended up as the largest vaccine producer in the world. It may be that Western countries tried to keep high IP, high margin cures in-house, and offshore the lower hanging fruit to places where labor was cheap. Also, India needs to vaccinate a larger number of people every year for standard diseases.

Edited by IheartIheartTesla

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12 minutes ago, IheartIheartTesla said:

Anyway, dont know how India ended up as the largest vaccine producer in the world. It may be that Western countries tried to keep high IP, high margin cures in-house, and offshore the lower hanging fruit to places where labor was cheap. Also, India needs to vaccinate a larger number of people every year for standard diseases.

This is a good story explaining it. It started with a snake venom vaccine and then the founders of SII moved on to polio. An astonishing 65% of the children in the world have received a Serum Institute vaccine. So it's a volume + cost story.

I have also seen stories that say it's possible because India is very rich in the chemical compounds required for vaccines. Something similar will happen over the next decade or two in Africa with regard to minerals required to manufacture batteries as we move to electric vehicles.

https://www.dw.com/en/coronavirus-vaccine-why-does-indias-serum-institute-have-a-head-start/a-55089750

Edited by Fragile Bird
forgot link!

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2 hours ago, Chataya de Fleury said:

An antibody test just says whether she’s had it and has detectable antibodies. Has nothing to do with infectiousness. She may have had it months ago. 

And her current symptoms could be a re-infection. Or a cold. She should at least get a rapid antigen test.

I can’t quite follow at this point, because his latest account says they had a nose and throat swab as well, which indicates a combined antigen and antibody test. He was negative for both and she was positive for something but I’m not sure what because I was too stressed to ask. 

it’d indeed be rather lucky if it was a weak reinfection. In fact it’s incredibly lucky that my father hasn’t caught it yet with so many of his colleagues and friends having been ill (they all recovered safely and quite quickly thank goodness). Either way, I’m hoping his nurse girlfriend will be of some use at least and test him every day for the next week with the rapid kits at least. 

2 hours ago, Filippa Eilhart said:

if she has a positive antibody test she’s 99,9% not infectious.

As detailed above.  Anyway, I thought that only long term antibody (igG) positivity indicated that. When I was tested the guy said the short term (igM) antibody positivity indicates that ones in the middle phase of covid, when they’re still infected (and infectious) but their immune system already had time to attack the virus. I might misremember that of course. 

 

maybe I’m just paranoid because my mum’s cousin’s husband died yesterday and he was younger than my father? That wasn’t covid related though. No, I don’t think I’m overreacting, I do honestly believe that they don’t handle precautions as they ought to. And this girl, I like her and all, but who goes to the office when they feel symptoms? 

Edited by RhaenysBee

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1 minute ago, RhaenysBee said:

I can’t quite follow at this point, because his latest account says they had a nose and throat swab as well, which indicates a combined antigen and antibody test. He was negative for both and she was positive for something but I’m not sure what because I was too stressed to ask. 

it’d indeed be rather lucky if it was a weak reinfection. In fact it’s incredibly lucky that my father hasn’t caught it yet with so many of his colleagues and friends having been ill.  Either way, I’m hoping his nurse girlfriend will be of some use at least and test him every day for the next week with the rapid kits at least. 

As detailed above.  Anyway, I thought that only long term antibody (igG) positivity indicated that. When I was tested the guy said the short term (igM) antibody positivity indicates that ones in the middle phase of covid, when they’re still infected (and infectious) but their immune system already had time to attack the virus. I might misremember that of course. 

Yeah, IgM antibodies appear soonest, and IgG are more long term. A gold standard antibody test will test for both. 

I was wondering if your father may have caught it asymptomatically at some point - though if too long ago, an IgG test won’t pick that up, either.

Sometimes the people you’d least expect to be asymptomatic are; my nail tech’s mom got it, and nt’s mom lives with 73 year old grandmother who has heart disease and diabetes. The grandmother was PCR tested positive, but had no symptoms, while the 42 year old mother had “a mild case” symptomatically.

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24 minutes ago, Chataya de Fleury said:

Yeah, IgM antibodies appear soonest, and IgG are more long term. A gold standard antibody test will test for both. 

I was wondering if your father may have caught it asymptomatically at some point - though if too long ago, an IgG test won’t pick that up, either.

Sometimes the people you’d least expect to be asymptomatic are; my nail tech’s mom got it, and nt’s mom lives with 73 year old grandmother who has heart disease and diabetes. The grandmother was PCR tested positive, but had no symptoms, while the 42 year old mother had “a mild case” symptomatically.

Ah okay, than my understanding wasn’t too misguided. 

He has been tested on occasion over the past year, so if he had caught it asymptomatically some test would have picked it up. I did wonder for a while if sister and I had it, but that would have been back in 2019 august and that’s kinda unlikely, though peculiar cases as such do come up here and there and there’s a lot of speculation if this or that illness had been covid as far back as 2018. But I don’t think we were that “lucky”, whatever bug we had caught then won’t give us COVID protection. 

yep, heard of a lot of similar cases. Covid passing through 60, 70, even 80 somethings without any major problems.  

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4 hours ago, IheartIheartTesla said:

There is a little bit of truth in the old Chris Rock routine, where he notes that the reason we dont have a cure/vaccine for cancer or diabetes, because all the money is to be made in having people come back every month for curing the symptoms. Anyway, vaccines are more one-and-done (or two-and-done), so I imagine in terms of a business model its not as profitable as a drug model. Even though the latter addresses a smaller portion of the entire population, its returns accumulate over time. There may also be money in formulating drugs (for instance, proper release profiles) that may allow for commanding better prices.

Anyway, dont know how India ended up as the largest vaccine producer in the world. It may be that Western countries tried to keep high IP, high margin cures in-house, and offshore the lower hanging fruit to places where labor was cheap. Also, India needs to vaccinate a larger number of people every year for standard diseases.

I think you're correct about how India developed vaccine manufacturing: the West lost interest because it's not profitable enough. That drugs that need to be taken for life is way more interesting to pharma than cheap vaccines is a key reason why the "This is a plot from Big Pharma" theory is just pure bogus.

And when it comes to producing vaccines, this shit is turning into a sad sick joke, truly: EXCLUSIVE-AstraZeneca to miss second-quarter EU vaccine supply target by half - EU official | Reuters

These scumbags don't just underdeliver in 1st quarter by 2/3, they're also going to underdeliver by 1/2 in 2nd quarter. Goddamn, EU really needs to get its shit together and approve other vaccines - even Sputnik it if comes to that and they can at long last provide solid and convincing data to EMA (not sure why this hasn't happened yet, whether it's EU that's suspicious or not interested, or the Russians who don't or can't deliver official data).

Edited by Clueless Northman

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The state of CT just announced the next tiers for vaccine eligibility.  After teachers and child care workers, they’re just jumping into age tranches.  55+ are eligible now, then 45+ are eligible from March 22nd.  I’ll be eligible in mid April, not that there’s any guarantee that there will be vaccine supply and appointments available.

The grocery store workers are pretty pissed off that they weren’t given priority as frontline/essential workers before the eligibility devolved to just age brackets.  They’re absolutely right.  I know Lamont is saying simple is better and it’s hard to enforce many criteria, but that’s no way to treat people who’ve shown up work in risky environments all this time.  

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