covid-19

[RandBlade]

Twitter Link

I wanna give her the benefit of the doubt here, but, in light of some of her previous statements of a similar nature, I don't think she deserves it.

The context of this apparently is they were* expecting mutations or variants to arise but they were unable to predict when they would or what effect the variants would have, which is why they were working on having spare capacity so that when a mutation arose there was already spare capacity in the system.

So the opposite of what the snipped quote implies. And a learning from earlier when capacity ran out after the back to school surge, it didn't over Christmas with testing reaching 700k per day following the new variant.

* Indeed they were actively sequencing the tests monitoring and looking for new variants. Most countries weren't even sequencing the tests.

[Aimless]

Thank you, that is the explanation I suspected when I said I wanted to give her the benefit of the doubt.

[RandBlade]

Yeah it was so illogical it leapt out.

Especially given the fact the UK had done so much sequencing was flagged up when the story about the variant broke - if they weren't expecting variants why would they be sequencing and analysing the variants? It didn't make sense.

[RandBlade]

Twitter Link

Twitter Link

LOL. So true.

[Aimless]

Just because its not been peer-reviewed yet doesn't make it wrong.

Anything above 50% efficacy from a single dose makes it virtually a truism that twice as many people vaccinated > half as many vaccinated. It would take a catastrophic bungling of the data to reduce efficacy at 3 weeks from one dose from an estimated 90% down to below 50%.

Plus as I said this isn't happening in a vaccuum. All the evidence that is accumulating allows us to set a reasonable hypothesis that a single dose by 3 weeks provides a great amount of immunity. That is the hypothesis that the JCVI, all 4 Governments of all the parties and all 4 CMOs are operating on. This data fits that hypothesis which should be very reassuring - if it did not it would be very concerning.

You're extrapolating from a questionable point estimate.

[Aimless]

Just because its not been peer-reviewed yet doesn't make it wrong.

Anything above 50% efficacy from a single dose makes it virtually a truism that twice as many people vaccinated > half as many vaccinated. It would take a catastrophic bungling of the data to reduce efficacy at 3 weeks from one dose from an estimated 90% down to below 50%.

Plus as I said this isn't happening in a vaccuum. All the evidence that is accumulating allows us to set a reasonable hypothesis that a single dose by 3 weeks provides a great amount of immunity. That is the hypothesis that the JCVI, all 4 Governments of all the parties and all 4 CMOs are operating on. This data fits that hypothesis which should be very reassuring - if it did not it would be very concerning.

You're extrapolating from a very questionable point estimate.

[RandBlade]

An estimate that has been demonstrated by at least about eight different studies so far, both double-blind and real life.

At what point do you stop and think "yes, people's lives could be saved by listening to these scientists"?

Anyway, we're now upto 10.5 million people vaccinated. Looks like the 15 million target will be met. So by the end of the month if the scientists are right then almost all vulnerable people will have a great deal of protection. That should be a remarkable turnaround and couldn't have been done if double dosing everyone.

[Aimless]

An estimate that has been demonstrated by at least about eight different studies so far, both double-blind and real life.

Which 8 different "double blind" and "real life" studies have clearly demonstrated ~90% efficacy for Comirnaty, after a single dose, over a 12 week period? I'm not saying that it's not effective, I'm strictly addressing the lack of evidence for those claims. Two separate issues. The latest preprint reads like a hastily cobbled-together Medium blog post, and the method does not appear compelling at all, so I'd be happy to read any better quality studies you may have found. The original Phase 3 trial data do not support the claim.

[Aimless]

Meanwhile:

Twitter Link

[RandBlade]

Which 8 different "double blind" and "real life" studies have clearly demonstrated ~90% efficacy for Comirnaty, after a single dose, over a 12 week period? I'm not saying that it's not effective, I'm strictly addressing the lack of evidence for those claims. Two separate issues. The latest preprint reads like a hastily cobbled-together Medium blog post, and the method does not appear compelling at all, so I'd be happy to read any better quality studies you may have found. The original Phase 3 trial data do not support the claim.

I never said over a 12 week period, nor did I say "90%" (since AZN most doses don't give that) I said "a single dose by 3 weeks provides a great amount of immunity".

If your hypothesis is that immunity drops like a stone from week 3 to week 12 then there's no evidence of that, that I'm aware of.

The Phase III data in every single trial showed a great amount of immunity (70%-90% depending upon vaccine) by week 3.

[RandBlade]

Concerning report about France.

Twitter Link

Its worrying seeing the rising case numbers there, combined with the protests, refusal to lockdown, the vaccine incompetence . . . and I'm worried this mess is going to play into the hands of Le Pen. All in all rather worrying.

[Aimless]

I never said over a 12 week period, nor did I say "90%" (since AZN most doses don't give that) I said "a single dose by 3 weeks provides a great amount of immunity".

If your hypothesis is that immunity drops like a stone from week 3 to week 12 then there's no evidence of that, that I'm aware of.

The Phase III data in every single trial showed a great amount of immunity (70%-90% depending upon vaccine) by week 3.

12 week interval is the specific policy to which this is supposed to apply. You have repeatedly referred to the 90% figure on this very page—in response to the headline figure in that article—and then said that that point estimate (mentioned once again in the post of yours that I quoted when I said you were extrapolating from a questionable point estimate) has been "demonstrated by at least about eight different studies so far, both double-blind and real life". But afaict no study has clearly done so for Comirnaty. The estimate based on the Pfizer phase 3 data has an extremely broad confidence interval—and becomes even more unreliable when you exclude the first two weeks. The validity of this latest study is questionable. Immunity conferred by a vaccine is likely to vary between individuals, and there's no need to posit that it will "drop like a stone" to be less than sufficient after a 12 week period—you just need to have a weaker initial response in a given individual. Again, these objections only concern what conclusions can (or, rather, can't) be drawn based on available evidence.

[RandBlade]

90% is this study and the trial, as well as the trials for other vaccines which are not the same but are all having a similar response pattern.

The 12 week interval is a reasonable assumption that the vaccine response won't fall in that time. I never said that had been demonstrated but it is a reasonable assumption to make if the immune response is as high as 90%.

Just because there is a confidence interval does not make it wrong to act with the information we have. We can't always be confident how a lockdown or other procedures will work either, or what will happen without them, but the best available decision needs to be made.

Though the worst antiscience nonsense is not the 4 nations of the UK each choosing to follow what their medical regulators and scientists recommended regarding the vaccines - it is the antivax pandering nonsense of Macron and others attempting to cover up not ordering enough AZN vaccine by saying not to use the AZN vaccine on the people who need it, the over 65s, after the EMA recommended using it - and just days after such a stink was raised about wanting more of it. Either the EMA is not fit for purpose and shouldn't have recommended it (not true), or this pandering to antivax bullshit is not something that responsible politicians should be doing.

[Aimless]

90% is this study and the trial

But that is what I'm objecting to. The trial data do not lend strong support to that estimate, and it is not prudent to extrapolate from a point estimate that is so shaky. The study we're now discussing may be even less useful. Meanwhile, the study it purports to refute is a relatively good study, that found more compelling evidence of substantially lower efficacy after a single dose—esp. among older people.

The 12 week interval is a reasonable assumption that the vaccine response won't fall in that time. I never said that had been demonstrated

Tbf:

It would take a catastrophic bungling of the data to reduce efficacy at 3 weeks from one dose from an estimated 90% down to below 50%.

You're extrapolating from a very questionable point estimate.

An estimate that has been demonstrated by at least about eight different studies so far, both double-blind and real life.

Just because there is a confidence interval does not make it wrong to act with the information we have.

I'm addressing only what you can say about the information we have.

Though the worst antiscience nonsense is not the 4 nations of the UK each choosing to follow what their medical regulators and scientists recommended regarding the vaccines - it is the antivax pandering nonsense of Macron and others attempting to cover up not ordering enough AZN vaccine by saying not to use the AZN vaccine on the people who need it, the over 65s, after the EMA recommended using it - and just days after such a stink was raised about wanting more of it. Either the EMA is not fit for purpose and shouldn't have recommended it (not true), or this pandering to antivax bullshit is not something that responsible politicians should be doing.

The EMA does not appear to have recommended using the AZN vaccine in the over 65 group; in their recommendation to authorize the vaccine, they state that it can be used in that group. There's nothing inconsistent about wanting more of the contractually promised AZN vaccine in order to be able to use it in young & middle-aged people, while prioritizing eg. Comirnaty for older people.

[wiggin]

Evidence and proof are not the same thing. In a rapidly evolving environment absolutely careful analysis and reanalysis of the data should occur.

This data is significant and should feed into that analysis and reanalysis. Unless something in the findings has gone wrong then a 90% level of protection should be quite statistically significant and it should feed into the evidence and analysis of what is going on. That it is real world evidence of matching the conclusions drawn from the clinical trials shouldn't be ignored or totally discarded.

I appreciate you would prefer a series of scientifically rigorous double blind controlled studies to test every hypothesis but we are in a pandemic today. Delay in responding to evidence can lead to thousands of lives being lost. If the study had shown instead of 90% protection just 10% protection from dose one that would be a reason to urgently rethink. But if that had happened would you calmly say it in "no way provides evidence"?

RB, I am not going to litigate this indefinitely with you. But a few points:

- The analysis was interesting but did not provide new data.
- The '90%' level of protection was the maximum efficacy projected based on a fairly suspect Bayesian analysis of a single day's efficacy (they conveniently chose the day on their plot that had maximum efficacy), and has 90% credible intervals that were both questionable and relatively broad. Also, astonishingly, they aren't even using the Israeli dataset, but estimating the Israeli dataset based on the published graphs.
- No one is disputing that the Pfizer or AZN or Moderna vaccines start to provide reasonable protection about two weeks after the first dose. The question is whether this initial efficacy provides adequate evidence to support a change in the dosing schedule that was confirmed to be efficacious over the longer term in a large and well controlled RCT. This reanalysis does not provide additional evidence for this question; rather at best it provides a re-estimate of initial efficacy in one retrospective study that may indicate the headline number from the Israeli data may have been pessimistic.

This reanalysis provided little if any additional justification for the UK government's choices in this matter. That was why I responded the way I did; it is extremely important for us to evaluate each dataset and analysis on its merits and draw appropriate conclusions from it. Your apparent glee was not justified in any way by the content of this preprint.

[Lewkowski]

From the NY Times:

"But over the last few weeks, as vaccination has become a top priority, the pattern has changed. Progressive leaders in much of the world are now struggling to distribute coronavirus vaccines quickly and efficiently:

Europe’s vaccination rollout “has descended into chaos,” as Sylvie Kauffmann of Le Monde, the French newspaper, has written. One of the worst performers is the Netherlands, which has given a shot to less than 2 percent of residents.
Canada (at less than 3 percent) is far behind the U.S. (about 8.4 percent).
Within the U.S., many Democratic states — like California, Illinois, Minnesota, New Jersey, New York and tiny Rhode Island — are below the national average. “The parts of the country that pride themselves on taking Covid seriously and believing in government are not covering themselves in glory,” The Times’s Ezra Klein has written.

The success stories

At the same time, there are clear success stories in places that few people would describe as progressive.

Alaska and West Virginia and have the two highest vaccination rates among U.S. states, with Oklahoma and the Dakotas also above average. Globally, Israel and the United Arab Emirates have the highest rates. Britain — run by Boris Johnson, a populist Conservative — has vaccinated more than 15 percent of residents."

[LittleFuzzy]

An estimate that has been demonstrated by at least about eight different studies so far, both double-blind and real life.

At what point do you stop and think "yes, people's lives could be saved by listening to these scientists"?

When the data supports it. I haven't seen eight different studies leading me to the conclusion you have. Let's look at the Pfizer. We have the Israeli study (not peer reviewed, so of questionable veracity) saying one thing. We have the study you love so much saying something radically different but it's also not peer-reviewed. We do remember the data from Pfizer, who said that their estimate of the single-dose efficacy was 52% and the confidence interval meant it might be higher or it might be lower than 50%. You know what that leads me to conclude? We cannot and should not be monkeying around with a single-dose approach with the Pfizer because its efficacy may well be under that 50% mark you insist is so magical for breadth of protection having a greater effect than more effective protection. The AZN vaccine has a higher estimated efficacy but the confidence interval for that estimate is HUGE, so once again, we can't actually have any confidence that it's above that 50% mark. Which again means actively following the two-dose regimen we have higher confidence in because with your strategy, someone who is vaccinated may just be flipping a coin as to whether they're actually protected or not.

[RandBlade]

Its only flipping a coin, or 52%, if you completely ignore the fact that the 52% was an average of 0% for the first few days and 90% after a couple of weeks.

Considering that we know and expect that it will take a few days for the vaccine to start working, and we know and expect that the protection after say 7-8 weeks should be close to the efficacy after 3 weeks, I see no justifiable reason to average those figures together.

The data for the first ~10 days should be discarded as they're before the vaccine kicks in.

[Aimless]

Stanford epidemiologist discovers 200% of Sweden's population has had covid:

Twitter Link

[gogobongopop]

I've been told in the last few days (by friends and family, and not experts) a couple of interesting things. I don't know whether they are true, so I'll ask here.

1. If you have a bad reaction to a vaccine (like I did with the AZN vaccine a few days ago), it'll mean you'll get stronger protection from it.

2. Younger people tend to get harsher reactions because their immune systems tend to be stronger.

Bullshit or not?

[LittleFuzzy]

Its only flipping a coin, or 52%, if you completely ignore the fact that the 52% was an average of 0% for the first few days and 90% after a couple of weeks.

Considering that we know and expect that it will take a few days for the vaccine to start working, and we know and expect that the protection after say 7-8 weeks should be close to the efficacy after 3 weeks, I see no justifiable reason to average those figures together.

The data for the first ~10 days should be discarded as they're before the vaccine kicks in.

The 52% is from Pfizer's clinical trials and I have not seen any indication they were "averaging" the efficacy the way you allege.

[Aimless]

The 52% is from Pfizer's clinical trials and I have not seen any indication they were "averaging" the efficacy the way you allege.

He's not really misrepresenting it; it's the overall efficacy for the interval between first and second dose, as reported in their December paper on Comirnaty's safety & efficacy. Almost all cases in the treatment group occurred within first couple of weeks. Problem is, the data is not sufficient to state that efficacy of a single dose is extremely high (from a couple of weeks onward) based on observations over the course of a week and change. Few observations, extremely broad confidence interval, and not necessarily generalizable to present circumstances.

[wiggin]

From the NY Times:

"But over the last few weeks, as vaccination has become a top priority, the pattern has changed. Progressive leaders in much of the world are now struggling to distribute coronavirus vaccines quickly and efficiently:

Europe’s vaccination rollout “has descended into chaos,” as Sylvie Kauffmann of Le Monde, the French newspaper, has written. One of the worst performers is the Netherlands, which has given a shot to less than 2 percent of residents.
Canada (at less than 3 percent) is far behind the U.S. (about 8.4 percent).
Within the U.S., many Democratic states — like California, Illinois, Minnesota, New Jersey, New York and tiny Rhode Island — are below the national average. “The parts of the country that pride themselves on taking Covid seriously and believing in government are not covering themselves in glory,” The Times’s Ezra Klein has written.

The success stories

At the same time, there are clear success stories in places that few people would describe as progressive.

Alaska and West Virginia and have the two highest vaccination rates among U.S. states, with Oklahoma and the Dakotas also above average. Globally, Israel and the United Arab Emirates have the highest rates. Britain — run by Boris Johnson, a populist Conservative — has vaccinated more than 15 percent of residents."

I am not sure this is so much a question of being progressive or conservative, but idiosyncrasies with each state and their rollout plans.

I heard an interesting story comparing Massachusetts (run by a moderate Republican) and Connecticut (run by a fairly standard to slightly lefty Democrat); MA has done substantially worse in terms of rollout and doses on hand than CT. It sounds like the basic infrastructure exists in each state to get shots into arms relatively efficiently (though not without some embarrassing and avoidable snafus). But MA has held the line on pushing to get the highest priority people vaccinated first, with a particular emphasis on reaching out to communities that are at higher risk but have traditionally been underserved wrt healthcare. CT has opted for a looser approach, resulting in more shots into arms faster - but at the potential cost of those arms being attached to people who are more likely to be white and affluent, precisely the demographics that have been impacted less heavily.

It's not clear to me what is the better public health choice or ethical choice, and I have a very low opinion of the rollout across the US in general. But it does raise interesting questions about whether a slower pace of shots in arms (at least initially) might potentially yield better public health improvements earlier on. That being said, the biggest success story in the world has had a pretty laissez faire attitude towards relatively loose criteria, with a clear emphasis on doses administered at all cost. But given that they're vaccinating at ~5 times the rate of the US, they can afford to be less choosy.

I've been told in the last few days (by friends and family, and not experts) a couple of interesting things. I don't know whether they are true, so I'll ask here.

1. If you have a bad reaction to a vaccine (like I did with the AZN vaccine a few days ago), it'll mean you'll get stronger protection from it.

2. Younger people tend to get harsher reactions because their immune systems tend to be stronger.

Bullshit or not?

I doubt we have the data to know on your first question. Worse reactions to a vaccine could be due to all sorts of factors, some of which might be tied to better protection (but could easily be tied to things like a prior history with the vector, comorbidities in the patient, etc.). A semi technical but still readable discussion can be found here: https://www.nature.com/articles/s41541-019-0132-6 (Also look at reference 32 for a more detailed discussion of your question.)

For your second question, it indeed appears that side effects are more pronounced among younger patients, at least based on the data reported to date.

[gogobongopop]

I doubt we have the data to know on your first question. Worse reactions to a vaccine could be due to all sorts of factors, some of which might be tied to better protection (but could easily be tied to things like a prior history with the vector, comorbidities in the patient, etc.). A semi technical but still readable discussion can be found here: https://www.nature.com/articles/s41541-019-0132-6 (Also look at reference 32 for a more detailed discussion of your question.)

For your second question, it indeed appears that side effects are more pronounced among younger patients, at least based on the data reported to date.

Interesting, thanks.

[RandBlade]

https://www.thetimes.co.uk/article/i...ives-vqp70xn3l
It’s official — delaying second dose of Covid vaccine saves lives (Paywall)

The first real-world data from the vaccine rollout shows “promising evidence” that justifies the delayed second dose approach, a senior government vaccine adviser revealed last night.

Professor Anthony Harnden, deputy chairman of the joint committee on vaccination and immunisation, said people who have been vaccinated are enjoying “high levels of protection from the first dose” which was reducing infections and saving lives.

Public Health England is expected to publish the data within days. It will guide Boris Johnson and his advisers as they finalise plans to ease the national lockdown. By yesterday the number of people vaccinated exceeded 11 million.

The data shows infection rates in the over-eighties have fallen dramatically in the past month.

[wiggin]

Why don't we wait to see the data. I highly doubt they know what you imply.

[Aimless]

https://www.thetimes.co.uk/article/i...ives-vqp70xn3l
It’s official — delaying second dose of Covid vaccine saves lives (Paywall)

The first real-world data from the vaccine rollout shows “promising evidence” that justifies the delayed second dose approach, a senior government vaccine adviser revealed last night.

Professor Anthony Harnden, deputy chairman of the joint committee on vaccination and immunisation, said people who have been vaccinated are enjoying “high levels of protection from the first dose” which was reducing infections and saving lives.

Public Health England is expected to publish the data within days. It will guide Boris Johnson and his advisers as they finalise plans to ease the national lockdown. By yesterday the number of people vaccinated exceeded 11 million.

The data shows infection rates in the over-eighties have fallen dramatically in the past month.

Has it been 12 weeks already? How time flies.

[Aimless]

Don't remember whether anyone posted this, but Switzerland recently withheld approval for AZN's vaccine:

https://www.reuters.com/article/us-h...-idUSKBN2A32GV

In other news, I'm sure to get tenure at Stanford once my paper "it's not so bad if you castrate all dudes Roman-style because everyone only loses 1 ball on average" is published.

[RandBlade]

Has it been 12 weeks already? How time flies.

Interesting to see you've joined the Toby Young 'Covid is no big deal, take the time to be 100% certain before doing anything' train of thought.

Next time you criticise someone for prevaricating on locking down I'll be sure to check if its been 12 weeks of prevarication or not yet.

[Aimless]

Every day, this man disgraces Stanford a little more:

Twitter Link

Interesting to see you've joined the Toby Young 'Covid is no big deal, take the time to be 100% certain before doing anything' train of thought.

Next time you criticise someone for prevaricating on locking down I'll be sure to check if its been 12 weeks of prevarication or not yet.

My point is that you're trying to draw conclusions that can't be drawn from the data that is currently available. It's not a call to change strategy, it's just a criticism of your reasoning. At the time when your corrupt and incompetent government was busy sacrificing tens of thousands of people to placate Rishi Sunak and one pub owner, the evidence for strict NPIs had already been established—and the lack of evidence for the measures they actually chose was also clear. You keep getting excited about reports that don't move the needle in any direction, like a confused puppy. For some reason, you seem incapable of understanding the substance of the posts written in response to your claims. I mean, I know why I think you're incapable of understanding, but...