covid-19

[RandBlade]

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[And other nations doing the same thing] Bonkers.

17 million people have been vaccinated with this vaccine in Europe (inc UK) alone. No evidence whatsoever it causes clots. But we do know Covid kills.

How many more times can this be fucked up? Absolutely unscientific bullshit: https://www.sciencemediacentre.org/e...1615761818.118

Also interesting to see once again bashing Astrazeneca when the numbers of thrombocytopenia events with the AZN vaccine are no more than should be expected, nor more than are being seen in Pfizer patients. Politics not science again.

[Lewkowski]

Who benefits from this decision?

[RandBlade]

Antivaxxers benefit. Patients lose out.

The reports of blood clots in patients who've received the AZN vaccine (and the Pfizer one too) are below the rate you'd expect from the general population with the numbers having been vaccinated. Though Covid patients are known to get it as a side-effect so if you want to avoid side effects proceeding with a safe, efficacious vaccine and reducing the number of people with Covid will reduce incidents of clotting and deaths.

The European Medical Agency like the MHRA (the EU and UK's FDA) sees no reason to stop. But certain countries for months now have vaccillated between throwing a strop that they don't have enough AZN vaccines (having ordered it late) and throwing a strop that its ineffective or unsafe despite the EMA saying otherwise.

Interestingly Pfizer has seen the same delays, the same blood clots (as everything will do, they happen naturally so some are to be expected purely coincidentally) but doesn't get the same hysterical hatred.

[Timbuk2]

As I understand it, it is statistically meaningless too. The number of blood clots and aneurysms occurring in the population who have had the AZ vaccination is no higher per capita than among the general population who have not.

Seems like since the first country to report clots amongst those who have had the AZ jab has prompted other countries to focus in their own AZ-vaccinated populations too, where they will of course find evidence of blood clots just as they would if they focus in on any other entirely random subset of the population. Only it is now newsworthy to report it for the AZ population.

[RandBlade]

As I understand it, it is statistically meaningless too. The number of blood clots and aneurysms occurring in the population who have had the AZ vaccination is no higher per capita than among the general population who have not.

Seems like since the first country to report clots amongst those who have had the AZ jab has prompted other countries to focus in their own AZ-vaccinated populations too, where they will of course find evidence of blood clots just as they would if they focus in on any other entirely random subset of the population. Only it is now newsworthy to report it for the AZ population.

Well said.

It all started with the EU very publicly muddying the waters, to cover up their own failing to invest in vaccine production with sufficient cash and sufficient time, and then the European media piling on and putting pressure on national politicians and regulators.

That original decision to start a very public and very pointless spat with AZ has resulted in this: the 8% reports, the refusal to roll it out to older people, fake news about side effects, now fake news about blood clots. All stemming from the original decision to pick a fight with Astrazeneca.

It has completely fucked up the vaccine rollout and the losers are the European people who are still dying in their thousands while there are tens of millions of doses of a vaccine with 90% efficacy, 80% from just one dose, sits in the fridge unused.

Tens of thousands are getting hospitalised while a way to halt that is left idle. All because of hubris and an attempt to save face.

[RandBlade]

One year ago today. Has not aged well at all. I wonder how many will learn lessons from this?

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[Aimless]

As I understand it, it is statistically meaningless too. The number of blood clots and aneurysms occurring in the population who have had the AZ vaccination is no higher per capita than among the general population who have not.

Seems like since the first country to report clots amongst those who have had the AZ jab has prompted other countries to focus in their own AZ-vaccinated populations too, where they will of course find evidence of blood clots just as they would if they focus in on any other entirely random subset of the population. Only it is now newsworthy to report it for the AZ population.

It's a little more complicated than that, and the difference is easier to understand when you compare the vaccines. Thrombotic/thromboembolic events have been reported after being administered Comirnaty, but the people who have received Comirnaty are almost all very old and have multiple illnesses, which make such events more likely. That is why there hasn't been much alarm over reports of clots after vaccination with Comirnaty. The Norwegian cases, in contrast, have been among people under 50, who are, in general, much less likely to experience such events. Some people are more likely than others to get different kinds of clots even at younger ages, eg. because they have a genetic predisposition—the frequency of which can vary between populations—and it's possible the cases reported occurred among such people. It's also possible they are/were ill in some other way that predisposes them to form dangerous clots. It could also genuinely be a fluke. But the decision to halt the rollout of AZN's vaccine wasn't made in a frivolous manner. Norway's covid situation is also very different from eg. that of England, with barely 3 new hospital admissions per million per day; it's not surprising that they have weighed the risks differently.

[RandBlade]

17 million people have received the vaccine across the continent of Europe and there's no evidence that its causing clotting. The EMA, the MHRA, the WHO all agree on this.

The Netherlands and Ireland are not in a position to say that people are not being hospitalised there. Norway maybe is a special exemption but in both the Netherland and Ireland and other nations too tens of thousands of vaccinations have been cancelled as a result. With case numbers as they are, with case fatality rates as they are, some of those cancelled appointments will die from Covid 19. Many more will be hospitalised.

[Timbuk2]

It's a little more complicated than that, and the difference is easier to understand when you compare the vaccines. Thrombotic/thromboembolic events have been reported after being administered Comirnaty, but the people who have received Comirnaty are almost all very old and have multiple illnesses, which make such events more likely. That is why there hasn't been much alarm over reports of clots after vaccination with Comirnaty. The Norwegian cases, in contrast, have been among people under 50, who are, in general, much less likely to experience such events. Some people are more likely than others to get different kinds of clots even at younger ages, eg. because they have a genetic predisposition—the frequency of which can vary between populations—and it's possible the cases reported occurred among such people. It's also possible they are/were ill in some other way that predisposes them to form dangerous clots. It could also genuinely be a fluke. But the decision to halt the rollout of AZN's vaccine wasn't made in a frivolous manner. Norway's covid situation is also very different from eg. that of England, with barely 3 new hospital admissions per million per day; it's not surprising that they have weighed the risks differently.

Makes sense, thankyou.

[Flixy]

17 million people have received the vaccine across the continent of Europe and there's no evidence that its causing clotting. The EMA, the MHRA, the WHO all agree on this.

The Netherlands and Ireland are not in a position to say that people are not being hospitalised there. Norway maybe is a special exemption but in both the Netherland and Ireland and other nations too tens of thousands of vaccinations have been cancelled as a result. With case numbers as they are, with case fatality rates as they are, some of those cancelled appointments will die from Covid 19. Many more will be hospitalised.

It seems premature to stop it yes, with the caveat that we don't have the information they have.

Important to note that (at least here) they're not cancelled, just on hold for two weeks while they investigate further to have more confidence it's safe. And it's not a large number that's postponed, because AstraZeneca is delivering slow as a turd anyway, so I don't expect this has a massive impact on the overall vaccination progress (provided the temporary pause is not extended, which would be bad).

I wonder if this will help or harm vaccination rates: on one hand it may cause vaccines to seem more dangerous than they are, on the other hand it sends a message of 'we investigates your concerns thoroughly before continuing' which may make people trust it more. It wouldn't surprise me (but would disappoint me a little) if this decision was taken more because it's been over the news and they want to make sure people don't lose faith in vaccines.

Edit: the comment about the amount of vaccinations being postponed being low might be wrong, I may have misread the numbers of AZ vaccines that were planned for the next two weeks. So ignore that (although since we're supply limited, a two week delay would also be caught up relatively fast).

[Aimless]

Just go pick up a few million from the supply at Halix

[RandBlade]

One assumes that Halix would be busy producing supplies for their contractual obligations in the order they're contractually due.

Are you still struggling with this concept? Still buying into conspiracy theories that there's something nefarious going on?

[RandBlade]

FFS another sheep following the herd with no evidence whatsoever.

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But at least they're not in a serious situation, Covid is behind us, there's no hospitalisations and no lives risked by delay right?

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What a monumental fuckup. All because some insisted upon putting petty politics ahead of saving lives.

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Thousands will die an avoidable death due to these calamitous decisions.

[RandBlade]

EU meets EU.

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[Aimless]

Makes sense, thankyou.

The cases in Germany seem to be even more important to investigate. 6-7 cases of venous sinus thrombosis might be what you'd expect to see in a group of that size (not taking risk factors into consideration) over the course of a year—not over the course of a couple of months, with an apparent temporal relationship with vaccination. I understand why German authorities are proceeding with caution.

[RandBlade]

Proceeding with caution would be to analyse the data properly, not stopping vaccinations without proper evidence.

A good impartial explainer here Tim by the BBC.

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Tragically the [very pro-EU normally] Economist Health editor has put it best in that video.

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[Aimless]

One of the four patients hospitalized in Norway—due to an as-yet unexplained condition strongly resembling disseminated intravascular coagulation shortly after getting AZN's vaccine—has now died. Afaict all of them are otherwise healthy HCWs. German authorities have reported at least 6-7 cases of cerebral venous sinus thrombosis shortly after vaccination, in a group where you might expect to see that many cases of CVST over the course of a year, rather than within the span of 2-3 months. The true incidence of CVST may indeed be higher than we usually suppose it to be, but, based on conservative and fairly well-established estimates of CVST incidence that haven't yet been rubbished, we're looking at ~4 times more CVST than expected—presumably within a comparatively young and healthy group, given that AZN's vaccine was previously deemed less appropriate for use in elderly patients, in Germany. Many commentators are failing to distinguish between prevalence and incidence, and also failing to acknowledge how little they know about the details of these specific cases.

The debate in Sweden has been very interesting. A number of high-profile Swedish scientists—who're very active on social media—spent a day or so gleefully mocking the stupid, ignorant, easily frightened and dysfunctional health agencies in other European countries, while boasting about our own rational and level-headed public health agency. "Post hoc, ergo propter hoc" snark all over the place. There was even a lot of galaxy-brain discussions about other countries' vulnerability to Russian disinfo. And then, today, our public health agency also announced that they'd be pausing the deployment of AZN's vaccine. A lot of people publicly beclowned themselves for literally no reason. Scientists need to be able to wait two days for essential info before forming firm opinions on complex issues.

In other news, my little sister, who's on an assignment in Côte d'Ivoire, may be getting vaccinated today—presumably with AZN's vaccine. She asked me yesterday if she should take it, and I said that it's better for her to be vaccinated now than to wait—and that she'd probably end up getting offered the same vaccine either way. She may be a little annoyed with me if she goes through with it and then reads about the latest developments. But it would feel good to know that she has some protection while she's there, and for when she comes home.

[RandBlade]

It is indeed sad to see the Swedish agency jumping on the antivaxx hysteria bandwagon. They were right to stand up to it and the Swedish scientists who stood up for scientific principles are good people.

Hundreds or thousands of extra people will die due to this insanity.

[RandBlade]

File under: No fucking shit Sherlock.

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What a remarkable outbreak of mass hysteria and herd mentality from people who are supposed to be smart.

At least the Italians had the honesty that this was politics not science.

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Shame on those who feed antivaxx bullshit. 17 million have been vaccinated in Europe alone you silly innumerate unscientific ridiculous fools.

Well done to all those scientists Aimless referred to who understand the concept of "post hoc ergo propter hoc" and the scientific method.

[wiggin]

RB, while it's entirely possible that the pause in vaccinations was unwarranted by the evidence (I frankly have not seen the evidence and am likely not qualified to evaluate the clinical outcomes described), it's hardly unusual for an experimental treatment to be paused to evaluate whether adverse events were related to the treatment or not. I don't think it necessarily represents a dereliction of duty or an inexcusable political stunt (assuming these decisions were made by the local regulator or public health officials in the countries in question).

People have adverse events all the time during clinical trials and in the rollout of new treatments. And every single adverse event needs to be appropriately investigated to determine whether it is tied to the treatment or coincidental. Sometimes the investigations don't require a pause in the use of the treatment, generally when they are isolated cases, the likelihood of a connection is low, and the severity of harm is modest. Sometimes, however, it's absolutely essentially to pause and take a step back to independently evaluate what happened - that's why DSMBs exist in trials, and that's why post-market surveillance is so important.

I have not followed the details of what happened, but it's not unreasonable to have a pause for a few days to evaluate some concerns, assuming they meet the criteria I outline above. Even if the underlying vaccine is generally safe and effective, with rapid scaleup and new manufacturing facilities, it's not uncommon to find surprises in quality, contaminants, etc. that were not anticipated in the original smaller scale trials. Caution is warranted, and just as there is a risk of delaying vaccinations with the concomitant effects on Covid-related morbidity, there is also a risk of rushing forward headlong with a rollout of an experimental vaccine without carefully keeping an eye out for surprises. Regulators and clinicians (and governments) routinely fail to find the right balance between these two risks, but it's far from clear what one should do in a given circumstance.

[RandBlade]

Absolutely a proper investigation needs to be held, but what happened here is not proper by any means.

There was no scientific evidence for what has happened this week - and not only was it understandable that there would coincidentally be some clotting incidents but they were not statistically significant - but there have been the same ratio of clotting incidents for both the Pfizer vaccine and the Moderna vaccine too. Unsurprisingly, because they're unrelated coincidences that happen when you've done millions of vaccinations.

So why was Astrazeneca halted but Pfizer and Moderna weren't? Despite them having the same coincidental clotting incidents? There is no good answer to this.

The criteria you outlined were not met which is why the EMA consistently said that the vaccines should continue. It is why the WHO consistently said the vaccines should continue. It was abandoning science, abandoning the EMA. To give them credit here the EU's organisation (the EMA) have called this absolutely correctly. It was the national ones that reacted with a form of hysterical cowardice, some even admitting it was political rather than scientific.

The EMA and the MHRA both publicly report any incidents, I'm guessing the FDA do something similar? The data was (and the EMA confirmed it again today) that there was no significant difference in clotting between the Astrazeneca and Pfizer vaccine both of which have had many millions of doses. Ludicrous then to pander to blocking one while ignoring the other.

[Aimless]

Thread on an update from the German regulator:

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The rest of the thread lays out the legal & ethical rationale. Bit pleased to see my off-the-cuff estimate of the discrepancy wrt CVST incidence held up, even though it wasn't age-adjusted. Waiting for more info re. the 20 or so cases of unexplained DIC. The EMA is following through with the expedited safety signal procedure it has activated, and a preliminary verdict can be expected on Thursday.

[Timbuk2]

Minx, these numbers are surely still too small to be statistically significant?

1 per million or 4 per million are of the same order of magnitude, and surely within the range of natural occurrence within a non-vaccinated population.

Not making any comment here on the pausing of the rollout, just querying this statistical significance from Germany.

[RandBlade]

Well said Tim.

There's been millions of doses given out, if you gaze hard enough you're going to find some noise to cherrypick in any set of figures.

[Aimless]

Minx, these numbers are surely still too small to be statistically significant?

1 per million or 4 per million are of the same order of magnitude, and surely within the range of natural occurrence within a non-vaccinated population.

Not making any comment here on the pausing of the rollout, just querying this statistical significance from Germany.

Yup. On its own, it's important enough to trigger the safety signal process, but small enough to vanish if it turns out the the recipients were overwhelmingly eg. younger women (not unlikely among HCWs); like I said earlier, the estimates of CVST being referenced in various discussions don't take risk factors into account. A caveat is that we really are talking about a close temporal relationship with a specific known exposure here. I get the impression the German regulator made its assessment & recommendation in light of the 20 or so cases of unexplained DIC across Europe. Our public health agency explicitly referenced those cases as the reason for its decision to pause rollout of AZN's vaccine until the cases can be evaluated. They also confirmed that the decision had been made after conferring with other European regulators, so my guess is that's what the others have based their respective decisions to temporarily pause deployment on. We should get a well-reasoned verdict on Thursday.

[LittleFuzzy]

Rand, you keep choosing to forget the fact that all these vaccines are going forward under emergency authorization and they HAVEN'T been as fully vetted as we usually require our vaccines to be to ensure there are not unexpected risks like this one may be.

Aimless, a question. It has been pointed out that clotting issues are a known complication arising from Covid itself. I know that infections cause issues in a number of ways: symptoms they cause to promote their spread (often things like coughing, increased mucus production, etc), symptoms arising from our bodies attempts to fight off an infection (fever being the classic example), along with any number of things which are just the body and its systems being haywire. I'm very weak on biological systems though. How plausible is it for the clotting issues associated with Covid to be arising as part of the immune response?

[RandBlade]

Rand, you keep choosing to forget the fact that all these vaccines are going forward under emergency authorization and they HAVEN'T been as fully vetted as we usually require our vaccines to be to ensure there are not unexpected risks like this one may be.

Not exactly. The UK granted the vaccine an emergency authorisation, because this is an emergency. We did that while still a member of the EMA for another three to four weeks, so any other EU nation could have done that, but no others did.

The EMA instead gave a conditional marketing authorisation which took much longer to process and is part of the reason why authorisation took months longer to occur in the EMA than it did in the UK. So its actually being used there as an authorised vaccine not an emergency one, though it isn't the standard style of authorisation. See here for an explainer of the difference: https://ec.europa.eu/info/live-work-...ation-eu_en#30

But also most significantly the EMA was the relevant body that has authorised this vaccine for Europe. Other nations in Europe, like the UK, could have chosen to do their own authorisation but they all deferred to the EMA instead as the relevant body for the European Union. The EMA continues to monitor the data coming in as part of its authorisation and quite simply has seen no issues and they have not rescinded the authorisation, nor given any hint it should be rescinded. Instead it has been stopped not by the relevant body monitoring its authorisation, its been stopped either by health bodies that didn't do the authorisation in the first place and don't have the expertise or data in some countries - and politicians acting alone without speaking to health bodies in others.

Had the EMA as the relevant body that has actually authorised the vaccine found a reason to suspend its authorisation that would be one thing, but that is not the story here. Macron pulled France's vaccine rollout unilaterally without even speaking to his own Health Secretary. Do you really think that's a scientific way to act?

This is not part of monitoring or vetting a vaccine that has been authorised, it would be like Trump as President seeing a dodgy news story on Fox, pulling the authorisation, against the advice of Dr Fauci and against the advice of the FDA.

[Aimless]

Aimless, a question. It has been pointed out that clotting issues are a known complication arising from Covid itself. I know that infections cause issues in a number of ways: symptoms they cause to promote their spread (often things like coughing, increased mucus production, etc), symptoms arising from our bodies attempts to fight off an infection (fever being the classic example), along with any number of things which are just the body and its systems being haywire. I'm very weak on biological systems though. How plausible is it for the clotting issues associated with Covid to be arising as part of the immune response?

It's a very good question. Our understanding of covid-associated clotting disturbances is incomplete, but it is indeed believed that the hyperinflammatory state we see in more severe cases of covid plays an important role in the inappropriate clotting that we see in those patients. There is a lot of crosstalk & feedback between systems that regulate the inflammatory immune response and systems that regulate clotting, and we see inappropriate clotting in many other conditions that come with a marked inflammatory response. However, the virus itself appears to also have somewhat unique properties that can—both directly and indirectly—cause inappropriate clotting, and these properties (eg. the specific ways in which it affects the inner layer of small blood-vessels) may be more important wrt the severe clotting disturbances. So I guess you might say the virus and our immune-system are both... clotting against us

[RandBlade]

After country after country in Europe has been gripped by temporary insanity (a few like Portugal, Belgium and Poland being sensible exceptions), with the EMA remaining sensible throughout, I see that von der Leyen has been unhappy at the national leaders being the ones to screw around so is now like "hold my stein".

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The UK and other countries aren't blocking exports of vaccines to Europe and Europe aren't sending vaccines to the UK etc. Companies within the UK and Europe are meeting their contractual obligations and countries like the UK are front of the queue because we paid more and invested earlier to get the vaccines. As we discussed months ago, though some here thought that spending more and signing contracts earlier wouldn't have an impact on rollout.

Now she's threatening to block exports, expropriate IP and worse all because her government fucked up negotiating contracts. The companies producing the vaccines will send them when they're produced and due in the list of contracts they've signed, that's how markets operate.

So much for Europe being a "rules based" organisation.

[Aimless]

the programmers among you will be happy to learn that the Spanish govt has decided to accelerate its Y2K mitigation programme in response to the pandemic

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