Developing the Covid-19 vaccine

[Woodchopper]

Here’s the EMA press release: https://www.ema.europa.eu/en/news/astra ... -low-blood

[raven]

If there are going to be restrictions placed on the use of the AZ vaccine with younger age groups - this is going to cause massive problems for the developing world.

This was supposed to be the vaccine that was affordable - sold on a non-profit basis - to low and middle-income countries. And these countries - because of the age structure of their populations - are those where a larger proportion of vaccinations would be in younger age groups.

Yep. It really sucks that AZ has hit this problem.

The EMA press release says most of the cases are women under 65. This is the demographic that take the pill and a quick google suggests the combined pill increases the risk of clots by 2 to 6 times, but I don't think many women avoid the pill because of that. Is that comparable to the incidence after AZ? I can't find base incidence of thrombosis to tell.

ETA: But I guess the clotting associated with the pill might be less serious. More DVT in the legs, less CVS and pulmonary clots perhaps.

[Gfamily]

The EMA press release says most of the cases are women under 65. This is the demographic that take the pill and a quick google suggests the combined pill increases the risk of clots by 2 to 6 times, but I don't think many women avoid the pill because of that. Is that comparable to the incidence after AZ? I can't find base incidence of thrombosis to tell.

ETA: But I guess the clotting associated with the pill might be less serious. More DVT in the legs, less CVS and pulmonary clots perhaps.

I think a specific difference is that in the AZ case, there is a close relation between the vaccination and the blood clot event - whereas the pill is likely to have been taken for an extended period before any problems emerge with a clot.

Overall, the risk from the pill is significantly higher, but the perception of risk differs.

[Woodchopper]

If there are going to be restrictions placed on the use of the AZ vaccine with younger age groups - this is going to cause massive problems for the developing world.

This was supposed to be the vaccine that was affordable - sold on a non-profit basis - to low and middle-income countries. And these countries - because of the age structure of their populations - are those where a larger proportion of vaccinations would be in younger age groups.

Yep. It really sucks that AZ has hit this problem.

The EMA press release says most of the cases are women under 65. This is the demographic that take the pill and a quick google suggests the combined pill increases the risk of clots by 2 to 6 times, but I don't think many women avoid the pill because of that. Is that comparable to the incidence after AZ? I can't find base incidence of thrombosis to tell.

ETA: But I guess the clotting associated with the pill might be less serious. More DVT in the legs, less CVS and pulmonary clots perhaps.

I think that there is a different calculation. An unplanned pregnancy brings risks of blood clotting and of course may other health and social problems. An individual woman and her doctor might decide that taking hormones is the most effective way of avoiding pregnancy. Other methods are available but they can involve severe side effects for some, or having to trust others to be careful.

With the vaccine, if stocks can be switched between different producers without affecting overall vaccination rates then an rare risk is reduced with no cost. Of course that is a big 'if' and the calculation won't be cost free if reduced use of the AZ vaccine reduces the overall speed of vaccination.

Another consideration is whether uptake of all vaccines will decrease if people perceive that the authorities aren't being very very careful.

[Sciolus]

With the vaccine, if stocks can be switched between different producers without affecting overall vaccination rates then an rare risk is reduced with no cost. Of course that is a big 'if' and the calculation won't be cost free if reduced use of the AZ vaccine reduces the overall speed of vaccination.

That also assumes that other vaccines don't also turn out to have severe but exceedingly rare adverse side-effects once a few tens of millions of doses have been administered. (They probably will.)

[shpalman]

EMA reviewing possible link between Johnson & Johnson vaccine and rare blood clots

[bob sterman]

EMA reviewing possible link between Johnson & Johnson vaccine and rare blood clots

It's another adenovirus vector vaccine isn't it?

I know the vaccines aren't IV but...

https://pubmed.ncbi.nlm.nih.gov/17148587/

"Acute thrombocytopenia has been consistently reported following intravenous administration of adenovirus"

"...adenovirus induces platelet activation and promotes the formation of platelet-leukocyte aggregates both in vitro and in vivo."

[Herainestold]

EMA reviewing possible link between Johnson & Johnson vaccine and rare blood clots

It's another adenovirus vector vaccine isn't it?

I know the vaccines aren't IV but...

https://pubmed.ncbi.nlm.nih.gov/17148587/

"Acute thrombocytopenia has been consistently reported following intravenous administration of adenovirus"

"...adenovirus induces platelet activation and promotes the formation of platelet-leukocyte aggregates both in vitro and in vivo."

Sputnik V is an adenovirus based vaccine and has no blood clot issues.

[headshot]

EMA reviewing possible link between Johnson & Johnson vaccine and rare blood clots

It's another adenovirus vector vaccine isn't it?

I know the vaccines aren't IV but...

https://pubmed.ncbi.nlm.nih.gov/17148587/

"Acute thrombocytopenia has been consistently reported following intravenous administration of adenovirus"

"...adenovirus induces platelet activation and promotes the formation of platelet-leukocyte aggregates both in vitro and in vivo."

Sputnik V is an adenovirus based vaccine and has no blood clot issues.

What you don’t know can’t hurt you...

[Woodchopper]

In a rare admission of the weakness of Chinese coronavirus vaccines, the country’s top disease control official says their effectiveness is low and the government is considering mixing them to give them a boost.

Chinese vaccines “don’t have very high protection rates,” said the director of the China Centers for Disease Control, Gao Fu, at a conference Saturday in the southwestern city of Chengdu.

Beijing has distributed hundreds of millions of doses in other countries while also trying to promote doubt about the effectiveness of Western vaccines.

“It’s now under formal consideration whether we should use different vaccines from different technical lines for the immunization process,” Gao said.

https://apnews.com/article/beijing-immu ... _medium=AP

[Herainestold]

In a rare admission of the weakness of Chinese coronavirus vaccines, the country’s top disease control official says their effectiveness is low and the government is considering mixing them to give them a boost.

Chinese vaccines “don’t have very high protection rates,” said the director of the China Centers for Disease Control, Gao Fu, at a conference Saturday in the southwestern city of Chengdu.

Beijing has distributed hundreds of millions of doses in other countries while also trying to promote doubt about the effectiveness of Western vaccines.

“It’s now under formal consideration whether we should use different vaccines from different technical lines for the immunization process,” Gao said.

https://apnews.com/article/beijing-immu ... _medium=AP

It is a bit misleading to quote efficacy numbers between different vaccines tested in different countries at different times. Any vaccine tested in Brazil with its lethal variants would likely have a low efficacy.

I am assuming there must be decent data for the Chinese vaccines that have been approved in different markets, even if they haven't gone through formal approval from the EMA or the FDA.

[sTeamTraen]

It is a bit misleading to quote efficacy numbers between different vaccines tested in different countries at different times. Any vaccine tested in Brazil with its lethal variants would likely have a low efficacy.

Why? Show your working. Define "likely" and "low".

As long at a mutation does not cause the virus to evade the mechanism of action of the vaccine, there is no a priori reason to expect that the efficacy of the vaccine would be any different. The vaccines probably encountered many different variants during testing, and their overall efficacy numbers are a result of how well they did against all of those. Just because certain variants are better at spreading among unvaccinated populations doesn't tell us anything about how they will perform when they encounter a vaccinated individual.

We can certainly be concerned that any given variant *might* bypass the vaccine, but that's independent of that variant's effects on the unvaccinated population.

[shpalman]

The Johnson & Johnson rollout in Europe has been 'proactively delayed'

It's way less effective at causing blood clots than the AstraZeneca one: only 6 cases of blood clots out of 6.8 million doses administered in the US, that's about 10 times less isn't it? It's not really competitive.

[bob sterman]

The Johnson & Johnson rollout in Europe has been 'proactively delayed'

It's way less effective at causing blood clots than the AstraZeneca one: only 6 cases of blood clots out of 6.8 million doses administered in the US, that's about 10 times less isn't it? It's not really competitive.

Inspired by Herainestold's comment earlier...

It is a bit misleading to quote efficacy numbers (efficacy at causing clots) between different vaccines tested in different countries at different times.

Serious point - different healthcare systems, different side effect surveillance systems, different demographics being vaccinated. It's not inconceivable that in the fragmented US healthcare system - clots could be under-reported.

[shpalman]

The Johnson & Johnson rollout in Europe has been 'proactively delayed'

It's way less effective at causing blood clots than the AstraZeneca one: only 6 cases of blood clots out of 6.8 million doses administered in the US, that's about 10 times less isn't it? It's not really competitive.

The European commission is seeking “urgent clarification” from Johnson & Johnson after the company’s “completely unexpected” announcement that it has decided to delay the deployment of its coronavirus vaccine across Europe following concerns in the US about a small number of blood clots.

"We're supposed to keep telling people we know it's safe based on the results of an analysis we haven't started yet and then mess about with the recommendations ourselves" said the EMA, "this completely undermines all our work in undermining confidence in the vaccine. How are we supposed to do this if the manufacturer behaves properly? Their job is to randomly generate trial efficacy numbers."

[shpalman]

oh now you mention it there were some cases of blood clots after the Johnson & Johnson vaccine

the EMA said it was “currently not clear whether there is a causal association between vaccination” and the conditions

because I mean what would be the chances of that happening.

I'm sure some UK doctors will blow the whole thing wide open

Marie Scully was alarmed and puzzled. “It didn’t make sense,” she said. The consultant haematologist at University College London hospital (UCLH) had seen patients with blood clots in the brain and low platelets before and, although it was unusual, she always knew why. But there was no reason for the condition of the young woman in her 30s she was treating in early March.

“Now when you have blood clots in the brain like that there’s always a cause, and it was difficult to pinpoint the cause,” said Prof Scully.

"I could have saved a lot of time if I'd noticed what everyone across the whole rest of Europe was banging on about at the time."

[Grumble]

oh now you mention it there were some cases of blood clots after the Johnson & Johnson vaccine

the EMA said it was “currently not clear whether there is a causal association between vaccination” and the conditions

because I mean what would be the chances of that happening.

I'm sure some UK doctors will blow the whole thing wide open

Marie Scully was alarmed and puzzled. “It didn’t make sense,” she said. The consultant haematologist at University College London hospital (UCLH) had seen patients with blood clots in the brain and low platelets before and, although it was unusual, she always knew why. But there was no reason for the condition of the young woman in her 30s she was treating in early March.

“Now when you have blood clots in the brain like that there’s always a cause, and it was difficult to pinpoint the cause,” said Prof Scully.

"I could have saved a lot of time if I'd noticed what everyone across the whole rest of Europe was banging on about at the time."

Think you’re being a bit harsh there shpalman. She clearly was paying attention to the news from Germany at the very least. In early March no countries had suspended the Astra-Zeneca vaccine, the first were on April 11.

[shpalman]

Stefano Paternò died in early March.

Several EU countries suspend AstraZeneca vaccine to investigate blood clot cases just over a month ago.

The EMA, of course, told them to stop being so silly.

About a week after that, Scientists at Greifswald teaching hospital claim they have discovered the cause of blood clots among a small number of AstraZeneca vaccine recipients.

“We began to exchange information with some colleagues from the rest of Europe. The German group had quite a lot of experience with this particular condition. They had exactly the same information, but they were a little bit reluctant to share it with other people because they were in the process of getting it published in one of the scientific journals,” he said.

The Germans finding the link actually made the news a month ago whereas this UK story is only coming out now. The UK team "heard from the German group" not vice versa.

[Grumble]

Stefano Paternò died in early March.

Several EU countries suspend AstraZeneca vaccine to investigate blood clot cases just over a month ago.

The EMA, of course, told them to stop being so silly.

About a week after that, Scientists at Greifswald teaching hospital claim they have discovered the cause of blood clots among a small number of AstraZeneca vaccine recipients.

“We began to exchange information with some colleagues from the rest of Europe. The German group had quite a lot of experience with this particular condition. They had exactly the same information, but they were a little bit reluctant to share it with other people because they were in the process of getting it published in one of the scientific journals,” he said.

The Germans finding the link actually made the news a month ago whereas this UK story is only coming out now. The UK team "heard from the German group" not vice versa.

Yes, and the doctor was puzzled by a case in early March. The article is being written now, but it’s all perfectly sensible in timeline with nothing to suggest the doctor wasn’t taking European news seriously at the time.

I want to know what happened to all the Norwegian worries about the Pfizer vaccine?

[Herainestold]

Still, Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a veteran of discussions about vaccine safety, rattled off a list of questions even before the news about the J&J vaccine broke. Why, he asked, would a vaccine lead to the production of antibodies against platelet factor 4? He emphasized that even when the FDA authorized the vaccine, the plan had been to carefully monitor for cases of thromboses. Offit sits on a key FDA committee involved in reviewing vaccine data.

“What you really would love to know,” Offit said, “is what is causing the immune response to platelet factor 4?”

Is some part of the adenovirus mimicking platelet factor 4? If so, would that same mimicry occur with other adenoviruses? There’s no clear answer. But Offit suspects it’s a class-wide problem, meaning the same phenomenon associated with AstraZeneca’s vaccine is associated with Johnson & Johnson’s.

“There is going to be something about the adenovirus — whether it’s adenoviral DNA or an adenovirus protein — that complexes with platelet factor 4. So that will be determined, I suspect soon.”

If it is related to an adenovirus then it should occur with the Sputnik V vaccine..

https://www.statnews.com/2021/04/13/res ... ome-clues/

[Woodchopper]

Summary of efficacy issues with the Chinese and Russian vaccines: https://blogs.sciencemag.org/pipeline/a ... -questions

Apparently the UAE is offering a third Sinovac dose.

[Woodchopper]

Still, Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a veteran of discussions about vaccine safety, rattled off a list of questions even before the news about the J&J vaccine broke. Why, he asked, would a vaccine lead to the production of antibodies against platelet factor 4? He emphasized that even when the FDA authorized the vaccine, the plan had been to carefully monitor for cases of thromboses. Offit sits on a key FDA committee involved in reviewing vaccine data.

“What you really would love to know,” Offit said, “is what is causing the immune response to platelet factor 4?”

Is some part of the adenovirus mimicking platelet factor 4? If so, would that same mimicry occur with other adenoviruses? There’s no clear answer. But Offit suspects it’s a class-wide problem, meaning the same phenomenon associated with AstraZeneca’s vaccine is associated with Johnson & Johnson’s.

“There is going to be something about the adenovirus — whether it’s adenoviral DNA or an adenovirus protein — that complexes with platelet factor 4. So that will be determined, I suspect soon.”

If it is related to an adenovirus then it should occur with the Sputnik V vaccine..

https://www.statnews.com/2021/04/13/res ... ome-clues/

As to Offit’s question:

On Friday, some of the first researchers to describe the condition published their observations in The New England Journal of Medicine. One team describes 11 patients in Germany and Austria; the other has observations on five patients in Norway. Both teams found the patients had unusual antibodies that trigger clotting reactions, which use up the body’s platelets and can block blood vessels, leading to potentially deadly strokes or embolisms.

The symptoms resemble a rare reaction to the drug heparin, called heparin-induced thrombocytopenia (HIT), in which the immune system makes antibodies to a complex of heparin and a protein called platelet factor 4 (PF4), triggering platelets to form dangerous clots throughout the body. Sickened vaccine recipients also had antibodies to PF4, the researchers found.

The researchers who studied the German and Austrian patients, led by clotting expert Andreas Greinacher of the University of Greifswald, had initially called the syndrome vaccine-induced prothrombotic immune thrombocytopenia; both teams now suggest a slightly simpler name: vaccine-induced immune thrombotic thrombocytopenia (VITT).

In their paper, Greinacher and his colleagues also speculate about a possible mechanism. Vaxzevria consists of an adenovirus engineered to infect cells and prompt them to produce the virus’ spike protein. Among the 50 billion or so virus particles in each dose, some may break apart and release their DNA, Greinacher says. Like heparin, DNA is negatively charged, which would help bind it to PF4, which has a positive charge. The complex might then trigger the production of antibodies, especially when the immune system is already on high alert because of the vaccine. An immune reaction to extracellular DNA is part of an ancient immune defense triggered by severe infection or injury, Greinacher notes, and free DNA itself can signal the body to increase blood coagulation.

Alternatively, the antibodies may already be present in the patients and the vaccine may just boost them. Many healthy people harbor such antibodies against PF4, but they are kept in check by an immune mechanism called peripheral tolerance, says Gowthami Arepally, a hematologist at the Duke University School of Medicine who is working as an external consultant with AstraZeneca on the issue. “When you get vaccinated, sometimes the mechanisms of peripheral tolerance get disrupted,” she says. “When that happens, does that unleash any autoimmune syndromes that you are predisposed to, like HIT?”

https://www.sciencemag.org/news/2021/04 ... er-becomes

[Woodchopper]

India reels amid virus surge, affecting world vaccine supply
The surge, which can be seen across India, is particularly alarming because the country is a major vaccine producer and a critical supplier to the U.N.-backed COVAX initiative.
https://chicago.suntimes.com/2021/4/13/ ... ine-supply

[sTeamTraen]

EU announces that mRNA (Pfizer and Moderna) vaccines are the future, presumably because of (in various proportions) /a/ the lack of reported side effects, /b/ the astonishing efficacy, /c/ the ease of tweaking them to meet future variants (the entire code of the Moderna virus was apparently written in 48 hours ), and /d/ the manufacturers not having f.cked them around with the deliveries.

Meanwhile Denmark has given up on AZ (although that apparently depends on J&J as a substitute, so watch this space).

Currently it looks like Mrs sTeamTraen will both get AZ, unless Spain also decides in the next couple of weeks that it's not worth the hassle to have a vaccine that they aren't giving to anyone over 65 (because of insufficient testing) or anyone under 60 (because of the blood clots issue). We're 60 and 63. I would happily wait another month or two for an mRNA vaccine, not least because even with a 2-month delay I'd have the second shot of Pfizer or Moderna (we are scrupulously respecting the 3 weeks here) before the second AZ shot (10-12 weeks).

[tom p]

The Johnson & Johnson rollout in Europe has been 'proactively delayed'

It's way less effective at causing blood clots than the AstraZeneca one: only 6 cases of blood clots out of 6.8 million doses administered in the US, that's about 10 times less isn't it? It's not really competitive.

The European commission is seeking “urgent clarification” from Johnson & Johnson after the company’s “completely unexpected” announcement that it has decided to delay the deployment of its coronavirus vaccine across Europe following concerns in the US about a small number of blood clots.

"We're supposed to keep telling people we know it's safe based on the results of an analysis we haven't started yet and then mess about with the recommendations ourselves" said the EMA, "this completely undermines all our work in undermining confidence in the vaccine. How are we supposed to do this if the manufacturer behaves properly? Their job is to randomly generate trial efficacy numbers."

You are, of course, massively misrepresenting the communications from the EMA.
Panickingly ceasing vaccination and then restarting it and ceasing it, which is what governments are doing, causes way more harm to public confidence and thus vaccine uptake than taking a few extra days or a couple of weeks to actually assess the data in full.
The number of people helped rather than harmed (or, if you prefer, saved rather than killed) by even the AZ vaccine is orders of magnitude different and so taking that time before acting, when there's a desperate need to get people vaccinated, is justified.