The U.K. reports more blood-clotting cases in people who received the AstraZeneca shot.

[maestrob]

Britain reported 30 cases of extremely rare blood clots in people who had received the AstraZeneca-Oxford vaccine, the same sort of events that have prompted some European countries to restrict use of the shot in certain at-risk age groups.

The reports represented 25 more cases than Britain’s medicines regulator had previously received, going some way toward addressing a mystery that has hung over safety concerns about the vaccine: why Britain had not observed the same phenomenon that has been seen in continental Europe, driving countries including France, Germany and Sweden to stop giving the shot to younger people, who are believed to be at higher risk from the rare clotting events.

Britain’s medicines regulator said that it had received reports of no such clotting cases in people who had received the Pfizer-BioNTech vaccine.

The clotting cases have generated concern because, scientists said, they were somewhat unusual. They involve blood clots combined with unusually low levels of platelets, a disorder that can lead to heavy bleeding.

The clotting events that have drawn the most concern, known as cerebral venous sinus thrombosis, entail clots in the veins that drain blood from the brain, a condition that can lead to a rare type of stroke. Those represented 22 of the 30 clotting cases that Britain reported this week.

But it is not clear whether any of the cases are linked to the vaccine. And even if they are, British and European regulators have said they were so rare that the vaccine should continue to be used.

On Thursday, Germany’s immunization commission, the STIKO, recommended that anyone younger than 60 who received an initial vaccination with AstraZeneca be given either Pfizer-BioNTech or Moderna shots as their second vaccine doses.

In reporting its updated case count, Britain’s medicines regulator said that “the benefits of the vaccines against Covid-19 continue to outweigh any risks, and you should continue to get your vaccine when invited to do so.” The European Union’s medicines regulator has also recommended that countries continue to use the AstraZeneca vaccine. Both agencies are continuing to investigate.

Scientists said on Friday that the overall risk of the particular clotting events that have drawn concern was extremely low: roughly one case in 600,000 recipients of the AstraZeneca vaccine in Britain. And it is difficult to know how common the cases are in the general population, given that it can be hard to diagnose. Scientists have said that case counts would inevitably rise among vaccinated people as doctors began looking more closely for the condition.

David Werring, a professor at University College London’s Institute of Neurology, said that the unusual presentation of the cases in vaccinated people was creating concern about possible links with the shot.

But, he said, “The key thing to remember is how rare these brain clots are, and how powerful the proven benefit of vaccination is against Covid.” He added that doctors and people who had received the AstraZeneca vaccine should be on the lookout for symptoms of the clotting events, like severe headaches or signs of a stroke.

“More research is urgently needed,” he said.

Melissa Eddy contributed reporting.

— Benjamin Mueller

https://www.nytimes.com/live/2021/04/02 ... irus-cases

[Holden Fourth]

Britain reported 30 cases of extremely rare blood clots in people who had received the AstraZeneca-Oxford vaccine, the same sort of events that have prompted some European countries to restrict use of the shot in certain at-risk age groups.

The reports represented 25 more cases than Britain’s medicines regulator had previously received, going some way toward addressing a mystery that has hung over safety concerns about the vaccine: why Britain had not observed the same phenomenon that has been seen in continental Europe, driving countries including France, Germany and Sweden to stop giving the shot to younger people, who are believed to be at higher risk from the rare clotting events.

Britain’s medicines regulator said that it had received reports of no such clotting cases in people who had received the Pfizer-BioNTech vaccine.

The clotting cases have generated concern because, scientists said, they were somewhat unusual. They involve blood clots combined with unusually low levels of platelets, a disorder that can lead to heavy bleeding.

The clotting events that have drawn the most concern, known as cerebral venous sinus thrombosis, entail clots in the veins that drain blood from the brain, a condition that can lead to a rare type of stroke. Those represented 22 of the 30 clotting cases that Britain reported this week.

But it is not clear whether any of the cases are linked to the vaccine. And even if they are, British and European regulators have said they were so rare that the vaccine should continue to be used.

On Thursday, Germany’s immunization commission, the STIKO, recommended that anyone younger than 60 who received an initial vaccination with AstraZeneca be given either Pfizer-BioNTech or Moderna shots as their second vaccine doses.

In reporting its updated case count, Britain’s medicines regulator said that “the benefits of the vaccines against Covid-19 continue to outweigh any risks, and you should continue to get your vaccine when invited to do so.” The European Union’s medicines regulator has also recommended that countries continue to use the AstraZeneca vaccine. Both agencies are continuing to investigate.

Scientists said on Friday that the overall risk of the particular clotting events that have drawn concern was extremely low: roughly one case in 600,000 recipients of the AstraZeneca vaccine in Britain. And it is difficult to know how common the cases are in the general population, given that it can be hard to diagnose. Scientists have said that case counts would inevitably rise among vaccinated people as doctors began looking more closely for the condition.

David Werring, a professor at University College London’s Institute of Neurology, said that the unusual presentation of the cases in vaccinated people was creating concern about possible links with the shot.

But, he said, “The key thing to remember is how rare these brain clots are, and how powerful the proven benefit of vaccination is against Covid.” He added that doctors and people who had received the AstraZeneca vaccine should be on the lookout for symptoms of the clotting events, like severe headaches or signs of a stroke.

“More research is urgently needed,” he said.

Melissa Eddy contributed reporting.

— Benjamin Mueller

https://www.nytimes.com/live/2021/04/02 ... irus-cases

The part of the article I bolded and put in italics is once again an example of fearmongering on the part of our media. "It isn't proved but we'll print it anyway". The worrying thing is that this will cause even more people to refuse the jab which can't be good if we want to make the pandemic, endemic. I simply see this as irresponsible journalism.

[maestrob]

Interesting that you should see it that way.

So you would rather that things should be hidden from the public? Really??

I find that withholding information is a terrible idea. The article makes clear that there has been no established link of these deaths to the vaccine, yet this kind of incident has not taken place with the other brands, which I certainly believe is information that the public should have. Let people know the reality of the situation and make their own decisions.

Nothing irresponsible here at all. Just because it's the N. Y. Times, you want to attack their reporting, is that it?

[Holden Fourth]

Nothing to do with the NYT and everything to do with balanced reporting. For example, not mentioned was the number of vaccinations already carried out in the UK as a fraction of the number of blood clot issues. There are probably other allergic reactions to any of the covid shots as there are with any medication and that hasn't been mentioned either. I could go on and I'm not singling out the NYT - this has been reported like this in other media outlets.

[barney]

But surely the part you bolded WAS responsible journalism, saying exactly what you think should be said?

[Holden Fourth]

But surely the part you bolded WAS responsible journalism, saying exactly what you think should be said?

Exactly which is why I put it in bold. Here is something from the SMH yesterday which takes a much more two sided approach.

By Liam Mannix
April 5, 2021 — 7.45pm

The Thrombosis and Haemostasis Society Australia and New Zealand, the country’s acting chief medical officer and the medical regulator, do not believe there is hard evidence yet of a link between AstraZeneca’s COVID-19 vaccine and a rare blood clotting syndrome.

A 44-year-old man who received the AstraZeneca vaccine remains in Melbourne’s Box Hill Hospital with a probable case of the rare syndrome, termed suspected vaccine induced prothrombotic immune thrombocytopenia (VIPIT).
A Melbourne man has developed a blood clot after taking the AstraZeneca vaccine.

“We cannot say there is a causal link. That’s the bottom line,” said Associate Professor Vivien Chen, lead author of the Thrombosis and Haemostasis Society’s just-released guidance on VIPIT. “This is a new, emerging syndrome. The scientific investigations to show causality have not been done.”

However, Professor Jim Buttery, head of epidemiology and signal detection at the Victorian immunisation safety service, said he now believed there was evidence of a link.

“Although not conclusively proven yet, it is likely there is a causal link between the AstraZeneca vaccine and this rare subset of thrombosis with thrombocytopenia,” he told The Age via email.

“Based on the data available to date at the moment it appears the UK detected 30 cases from 18 million doses of vaccine, approximately 1 in 500,000 doses.”

Available evidence suggests the syndrome is extremely rare. Norway has reported a rate of 1 in every 25,000 doses, Germany has reported a rate of 1 in 100,000, while Europe’s overall figures are 1 in 210,000. Britain has recorded a much lower rate: 30 reported cases from 18.1 million AstraZeneca injections – around 1 in 500,000.

In comparison, a 65-year-old has between a 1 or 2 in 100 chance of dying if infected with COVID-19, with that risk continuing to rise with age.

The European Medicines Agency and Australia’s Therapeutic Goods Administration say the benefits of the vaccine continue to outweigh any risks.
Related Article
Doses of the AstraZeneca COVID-19 vaccine are seen at the Boigu community centre on March 24, 2021 in Boigu Island, Australia. COVID-19 vaccinations have started ahead of schedule in the Torres Strait, with health authorities bringing forward the coronavirus vaccine rollout amid growing concerns of an outbreak in the remote region as nearby Papua New Guinea grapples with a COVID-19 epidemic.
Coronavirus pandemic
Concerns that AstraZeneca clotting case may hurt public confidence in vaccine

Initially, much of the focus was whether AstraZeneca’s vaccine may raise the overall risk of blood clots. There is now evidence to show this is not the case. However, that concern turned out to be something of a red herring.

Our blood is filled with platelet cells, which are able to clot together when we are bleeding and clog the wound. This is why you stop bleeding soon after cutting yourself.

Cases of VIPIT are characterised by four things: low levels of platelets, high levels of blood clotting breakdown products, the formation of blood clots, and the presence of a specific antibody that over-activates platelets in the blood.

“It’s predominantly blood clots in what we would call unusual places,” said Dr Chen.

The unusual antibodies are a hallmark of the syndrome. They activate the platelets, which has the dual effect of causing blood clots to form while also removing other platelets from the bloodstream.

“There are several mechanisms by which the antibodies could develop , and as yet we don’t know the exact mechanism,” said Professor Paul Monagle, a paediatric haematologist at the University of Melbourne who is studying the syndrome.

“One possibility is it is creating antibodies, and those antibodies are recognising some sequence on the platelets, instead of the vaccine.”

Potential risk factors also remain unclear. Most of the cases reported so far were in women younger than 55.

That has led several European countries to stop giving AstraZeneca to people aged under 60. However, it could be that age and gender are not risk factors. Many European countries gave AstraZeneca to younger groups first, as well as healthcare workers – of which a large proportion are women.

Liam Mannix

In the article I've bolded one statement and put another in italics. They reflect opposing views and what I applaud Liam Mannix for is how he has put them on the same part of the article. This gives me, the reader, the chance to see that there are two points of view and I am free, right or wrong, to make up my own mind. As a journo Barney, surely this is what you would like to see? When I compare this to the NYT article and one from the UK it's like a breath of fresh air.

Finally, Mr Mannix didn't treat me, the reader, like I was a 12 year old with limited discernment. I learnt a lot about this syndrome from his SMH piece.

[maestrob]

G'day, Holden.

Your article does provide more information, including the speculation that there probably is a causal link. The N. Y. Times wisely (I think) decided not to include that bit of information (perhaps because America is now populated by too many anti-vaxxers who would seize on this?), as nothing has yet been proven.

Although I'm certainly not a scientist, I am indeed concerned that this syndrome of blood clotting has only turned up in people who have had the Astra-Zeneca vaccine, however rare such incidents may be. I'm also thankful that our approval process has held up the distribution of that vaccine in the United States. Given that company's flawed and hasty reporting of their trial data, and now this latest problem, I have my doubts that it will be offered here.

I also think that the EU acted hastily in approving the A-Z vaccine for use there, and that they continue to urge people to take it astounds me.

If I were in your shoes, I certainly would not take it. Innocent until proven guilty may work in the courtroom, but that's not good enough for something that I'm Injecting into my body, especially when other brands are available without any such baggage.

[maestrob]

A vaccine official says there is a link between AstraZeneca’s shot and rare blood clots.

A top vaccines official at the European Medicines Agency said on Tuesday that AstraZeneca’s vaccine was linked to blood clots in a small number of recipients, the first indication from a leading regulatory body that the clots may be a real, if extremely rare, side effect of the shot.

The agency itself has not formally changed its guidance, issued last week, that the benefits of the AstraZeneca vaccine outweigh the risks. It said on Tuesday that its review was ongoing and that it would announce its findings this week. But any further ruling from regulators would be a setback for a shot that Europe and much of the world are relying on to save lives amid a global surge in coronavirus cases.

The medicines agency said last week that no causal link between the vaccine and rare blood clots had been proven. Only a few dozen cases of blood clots have been recorded among the many millions of people who have received the vaccine across Europe.

But the vaccines official, Marco Cavaleri, told an Italian newspaper that “it is clear there is an association with the vaccine.” He said that it would likely remain up to individual countries to decide how to respond, given the variation in supply of Covid-19 vaccines and in the state of the virus.

Those comments represented the first indication from a member of a leading regulatory body that the blood clots could be a genuine, if extremely rare, side effect of the AstraZeneca vaccine. Previously, health officials in several European countries temporarily restricted the use of the shot in certain age groups, despite the European Medicines Agency’s recommendation to keep administering it.

Regulators in Britain and at the World Health Organization have also said that, while they were investigating any rare side effects, the shot was safe to use and would save many lives.

Mr. Cavaleri told the Italian newspaper Il Messaggero that European regulators had not determined why the vaccine might be causing the rare blood clots, which generated concern because the cases were so unusual. They involved blood clots combined with unusually low levels of platelets, a disorder that can lead to heavy bleeding.

The most worrisome of the conditions, known as cerebral venous sinus thrombosis, involves clots in the veins that drain blood from the brain, a condition that can lead to a rare type of stroke.

The clots are, by all accounts, extremely rare. European regulators were analyzing 44 cases of cerebral venous sinus thrombosis, 14 of them fatal, among 9.2 million people who received the AstraZeneca vaccine across the continent. Emer Cooke, the European Medicines Agency’s director, said that the clotting cases in younger people translated to a risk for one in every 100,000 people under 60 given the vaccine. Younger people, and especially younger women, are at higher risk from the brain clots, scientists have said.

In Britain, regulators last week reported 30 cases of the rare blood clots combined with low platelets among 18 million people given the AstraZeneca vaccine, which was developed with the University of Oxford. No such cases were reported in people who had received the Pfizer-BioNTech vaccine in Britain.

Regulators in Britain have said that people should get the vaccine “when invited to do so.” But British news reports indicated Monday night that regulators were considering updating that guidance for certain age groups.

Monika Pronczuk and Emma Bubola contributed reporting.

— Benjamin Mueller

https://www.nytimes.com/live/2021/04/06 ... irus-cases

[maestrob]

U.K. says AstraZeneca alternative should be offered for under 30s, and E.U. finds a ‘possible link’ to rare clots.

Britain said on Wednesday that it would offer alternatives to the AstraZeneca vaccine for adults under 30 as European regulators described a “possible link” with rare blood clots, a setback for the world’s most widely used vaccine and a blow to the more than 100 countries relying on it to save lives amid a global surge in coronavirus cases.

The European regulator, the European Medicines Agency, stopped short of advising that use of the vaccine be curbed in the 27 European Union countries, saying that it was up to the national authorities to decide who should receive which vaccine.

Until the announcement, Britain had never wavered in its use of the vaccine, making it a holdout in Europe even as many countries detected unusual, sometimes fatal, blood clots in some recipients. But evidence has mounted that very small numbers of Britons had also been afflicted, forcing the country to reduce the use in younger people of a vaccine that is the backbone of its world-beating inoculation program.

The concern over the blood clots has threatened the pace of vaccinations far beyond Europe. At least 111 countries of varying income levels have administered doses of AstraZeneca’s shot, making it international aid groups’ most potent weapon in the battle to reduce deaths in the vaccine-starved global south.

British and European regulators both said it was possible that the clots were linked to the vaccine, but that more investigation was needed. European regulators described the cases as a serious but “very rare” side effect.

The agency reiterated that the overall benefits of the vaccine still outweighed the risks, but urged that health professionals and recipients of the shot be cautious about symptoms like shortness of breath, chest pain or leg swelling.

Many European countries have restricted use of the vaccine in younger people because some scientists believe they are at higher risk of developing the rare blood clots. They are also at lower risk of severe Covid-19, raising the safety bar for any vaccine being given to younger people.

But the regulator said that it had not concluded that age or gender were a specific risk and that it would further investigate the issue.

“This case clearly demonstrates one of the challenges posed by large scale vaccination campaigns,” Emer Cooke, the agency’s head, said in a news conference on Wednesday. “When millions of people receive these vaccines, very rare events can occur that were not identified during the clinical trials.”

No other vaccine has stirred as much controversy as the shot made by the British-Swedish company, setting off spats with the bloc over cuts in supply, its efficacy and finally over rare, but sometimes fatal, blood clots reported in some recipients.

Those concerns led several European countries to first restrict the use of AstraZeneca in older age groups, then suspend it over reports of blood clots, only to roll it out again last month after the European Medicines Agency issued a preliminary opinion that the benefits of the vaccine outweighed the risks.

As doctors reported a higher incidence of serious blood clots in younger people, some countries decided to stop administering the shot to anyone younger than 55.

Europe’s concerns over the vaccine’s side effects are also likely to threaten global inoculation efforts, with much of the developing world depending on the AstraZeneca vaccine to tackle the pandemic. The shot is the cornerstone of Covax, a program designed to make vaccine access more equitable worldwide.

The vaccine appeared to be causing an immune reaction in which antibodies bind to platelets, activating them, German doctors and the European Medicines Agency have said. Those platelets, in turn, were causing the formation of dangerous clots in certain parts of the body, including in veins that drain blood from the brain, leading in some cases to a rare type of stroke.

Why the antibodies develop in these people is not known, doctors have said. Some component of the vaccine, or excessive immune reaction — or both — could be the cause, they said.

No pre-existing conditions are known to make patients more vulnerable to this clotting disorder after a vaccination, European regulators said.

— Benjamin Mueller, Monika Pronczuk and Matina Stevis-Gridneff

https://www.nytimes.com/live/2021/04/07 ... irus-cases

[Holden Fourth]

...and possibly looking to the future......

https://www.news.com.au/technology/inno ... bc24cfe4fa

Let's hope that work and human trials occur once again. I like the idea of having control of something that we've developed ourselves.

[maestrob]

...and possibly looking to the future......

https://www.news.com.au/technology/inno ... bc24cfe4fa

Let's hope that work and human trials occur once again. I like the idea of having control of something that we've developed ourselves.

I'd say that looks promising indeed. I really don't like that EU and British regulators are still recommending Astra-Zeneca's shot, as are the authorities in Australia. If I were living in a country with such low infection rates, I'd be very hesitant about having the A-Z shot.

Since the Pfizer vaccine is authorized for use there, I'd insist on having that one at this point.

[maestrob]

More countries pause AstraZeneca vaccine use amid warnings on rare blood clots.

A day after European regulators described a “possible link” between AstraZeneca’s Covid-19 vaccine and rare blood clots, the drug faced increasing hurdles on Thursday as countries around the world move to restrict its use in younger people. The decisions are the latest setback for AstraZeneca, the world’s most widely used coronavirus vaccine.

Although European regulators said that the vaccine’s benefits outweighed the risks for most people, several countries are now using the AstraZeneca shot only on older people who are most at risk of dying from the coronavirus. The Philippines said that it would temporarily stop administering the vaccine to people age 60 and under.

South Korean officials said that they would decide this weekend whether to resume administering the shot to people 60 and younger after a panel of experts reviewed the information on blood clots on Thursday.

Late Wednesday, Belgium said that it would temporarily halt use of the vaccine in people under 56, and that younger people will be offered alternative vaccines — measures that the country’s health ministry said would be reviewed in four weeks. Others, including Cameroon, the Democratic Republic of Congo, Denmark and Norway, have suspended use of the vaccine altogether until more information about the clotting risk is available.

Prime Minister Scott Morrison of Australia said at a news conference late Thursday that the country had changed its guidance on the AstraZeneca vaccine for younger people out of an abundance of caution. It now recommends that adults under 50 be given an alternative vaccine.

“We expect that this will require some changes to the arrangements we have as part of the vaccination rollout,” Mr. Morrison said during the briefing. Public health experts and the prime minister were clear that the decision was based on weighing the very low risks of complications from the vaccine against the risk of the coronavirus.

“Our purpose here tonight is to reassure Australians — to reassure them that we’ve been very clear about what the very low level of risk is here,” Mr. Morrison said.

In the Philippines, Rolando Enrique Domingo, the director general of the country’s Food and Drug Administration, said that there had been no local reports of blood clots, but that the government was taking a precautionary step after the European Medicines Agency’s decision to list clots as a rare side effect of the AstraZeneca vaccine.

In the meantime, he said, inoculations using the Chinese-produced Sinovac vaccine will continue.

“We await results of the review being done by our local experts, as well as the official guidance of the W.H.O.,” Mr. Domingo said, referring to the World Health Organization.

— Jason Gutierrez, Monika Pronczuk and Megan Specia

https://www.nytimes.com/live/2021/04/08 ... irus-cases

[Holden Fourth]

...and this from the only media publication I read on a daily basis.

THE SQUIZ

Just as Australia hits the 1 million mark of COVID vaccines administered, PM Scott Morrison last night fronted the media to say he'd received advice that adults aged under 50yo who have not already received their first dose of AstraZeneca vaccine should be given the Pfizer vaccine going forward. The AstraZeneca vaccine should only be given to those aged under 50yo where the benefit of being immunised against the coronavirus "clearly outweighs the risk for that individual's circumstances." It's not a directive, he said, but it's what the government’s expert vaccine advisory body has recommended.

THIS IS ABOUT THE RISK OF BLOOD CLOTS?

Yep. Yesterday, the European Medicines Agency said there is the possibility of patients developing very rare cases of blood clots within two weeks of vaccination with the AstraZeneca jab, and our government tasked its official advisers to look at it. There have been reports of a slightly higher incidence of clots reported in younger adult age groups in the range of 4-6 cases per million vaccine recipients. "To put that in some sort of perspective, the combined oral contraceptive pill - that can include adverse side effects [of blood clots] - that's 7-to-10 per 10,000." But the cases of blood clots after receiving the AstraZeneca vaccine have shown a 25% death rate, and advice from the Aussie experts is to target its rollout to those aged 50yo and over.

SO WHAT DOES THAT MEAN FOR GETTING AUSSIES VACCINATED?

Good question - and watch this space… Last night, Morrison said there will "be a recalibration" to "take into account the decision the government has taken tonight" - but it looks like plans to have all willing Aussie receive at least one dose of a vaccine by October are dashed. The Pfizer-produced vaccine is in circulation, and there will need to be a process of “prioritisation”, and the government will now have to “work through the logistics of that," Morrison said. Which is a good time to note that Australia has done deals with 4 vaccine producers for almost 150 million doses at the cost of $3.3 billion - and the AstraZeneca vaccine makes up 53.8 million of those. Labor leader Anthony Albanese yesterday said that the episode has shown “the Federal Government should have secured more deals” with other vaccine producers. The National Cabinet is meeting today where this will be the top agenda item.

I guess this will push me well and truly up the list for getting vaccinated depending on what Cabinet decide today. Not that I'm bothered either way, I'll just have it when it's available to me

[barney]

...and possibly looking to the future......

https://www.news.com.au/technology/inno ... bc24cfe4fa

Let's hope that work and human trials occur once again. I like the idea of having control of something that we've developed ourselves.

I'd say that looks promising indeed. I really don't like that EU and British regulators are still recommending Astra-Zeneca's shot, as are the authorities in Australia. If I were living in a country with such low infection rates, I'd be very hesitant about having the A-Z shot.

Since the Pfizer vaccine is authorized for use there, I'd insist on having that one at this point.

I'd like to Brian, but it would mean waiting till 2027 to get a vaccine. The Government has really mucked this one up.

[Holden Fourth]

Priority should be given to those most important - the front line workers including

Top of the list:

border control
emergency services
MIQ staff -that's anyone who works in the building at any point
Vaccine distributors
all medical staff including doctors, nurses, dentists, hospital employees, etc, etc.
Airline staff involved in any way with the possibility of coming in contact with infected people

It's only then we look at the vulnerable such as our fragile elderly and those with comorbidities.

I don't appear anywhere there and am happy to wait. We've got a chance to get it right this time.

[barney]

Well, we don't seem to be going so well so far. Lucky we are an island and can keep out all those pesky people who want to come and bring Covid with them.

[maestrob]

Well, we don't seem to be going so well so far. Lucky we are an island and can keep out all those pesky people who want to come and bring Covid with them.

The one positive takeaway from all this is that we seniors seem not to develop blood clots the way youngsters do, thus the EU has decided to stop using the vaccine in those under 55-60, while England has limited its use to those under 30. The problem seems to occur more often in women than in men.

https://www.theguardian.com/society/202 ... -regulator

[maestrob]

Blood Clots Linked to AstraZeneca Vaccine Stem From Rare Antibody Reaction

New studies from Germany and Norway examined cases involving mostly younger people who developed serious and sometimes fatal blood disorders.

By Denise Grady
April 9, 2021

New research has identified unusual antibodies that appear to have caused, in rare cases, serious and sometimes fatal blood clots in people who received the Covid vaccine made by AstraZeneca.

Exactly why the rare reactions to the vaccine occurred is still a mystery.

Scientific teams from Germany and Norway found that people who developed the clots after vaccination had produced antibodies that activated their platelets, a blood component involved in clotting. The new reports add extensive details to what the researchers have already stated publicly about the blood disorder.

Younger people appear more susceptible than older ones, but researchers say no pre-existing health conditions are known to predispose people to the rare reaction. That is worrisome, they say, because there is no way to tell if an individual is at high risk.

Reports of the clots have already led a number of countries to limit AstraZeneca’s vaccine to older people, or to stop using it entirely. These cases have dealt a crushing blow to global efforts to halt the pandemic, because the AstraZeneca shot — easy to store and relatively cheap — has been a mainstay of vaccination programs in more than 100 countries.

The European Medicines Agency, the regulator for the European Union, has emphasized repeatedly that the clotting disorder is rare, and that the vaccine’s benefits far outweigh its risks. But when a side effect has the potential to be devastating or fatal — like the blood clots in the brain linked to this vaccine — some regulators and segments of the public are finding that the risk is unacceptable, even if it is extremely rare.

As of Sunday, European regulators had received reports of 222 cases of the rare blood-clotting problem in Britain and the 30-nation European Economic Area (the European Union plus Iceland, Norway and Liechtenstein). They said that about 34 million people had received the AstraZeneca vaccine in those countries, and that the clotting problems were appearing at a rate of about one in 100,000 recipients.

European regulators said that as of March 22, they had carried out detailed reviews of 86 cases, 18 of which had been fatal.

The safety bar for vaccines is set high, because they are given to healthy people. The seemingly greater vulnerability of younger people to the clotting disorder is of particular concern, because their risk of severe illness from Covid itself is lower than that in older people. Those differences suggest that overall, compared to older people, younger people may have less to gain and more to lose from the AstraZeneca vaccine.

Germany, the Netherlands, the Philippines, Portugal and Spain have recommended that the AstraZeneca vaccine be given only to people over 60. Canada and France have limited it to those over 55; Australia, over 50; Belgium, over 56. Britain, where the vaccine was developed, has been its staunchest defender, but announced on Wednesday that it would begin offering alternative shots to people under 30.

The University of Oxford, which developed the vaccine with AstraZeneca, said on Tuesday that it had suspended a two-month-old trial of the vaccine in children and teenagers in Britain while it waits for regulatory guidance.

Cameroon, the Democratic Republic of Congo, Denmark and Norway have stopped using the vaccine.

Full vaccination with the AstraZeneca vaccine requires two doses, but regulators in France and Germany have recommended that people under 55 who have had one dose get a different vaccine for their second shot.

The AstraZeneca vaccine is not authorized for use in the United States, but the company has said it plans to apply to the Food and Drug Administration for permission for emergency use. The agency declined on Friday to comment on the rare clotting disorder.

On Wednesday, the European Medicines Agency said that the vaccine’s labeling should be revised to include listing the clotting disorder as a “very rare” side effect of the vaccine.

In a statement on its website, AstraZeneca said it was “actively collaborating with the regulators to implement these changes to the product information and is already working to understand the individual cases, epidemiology and possible mechanisms that could explain these extremely rare events.”

The two new studies were published by The New England Journal of Medicine. One from Germany described 11 patients, including nine women ages 22 to 49. From five to 16 days after vaccination, they were found to have one or more clots. Nine had cerebral venous thrombosis, a clot blocking a vein that drains blood from the brain. Some had clots in their lungs, abdomen or other areas. Six of the 11 died, one from a brain hemorrhage.

Although most of the patients were female, it is not known whether women are more vulnerable than men. Many health care workers in Germany are women, and they were among the first to be vaccinated.

One patient had pre-existing conditions that affected clotting. During a news briefing on Friday, Dr. Andreas Greinacher, an author of the report, said those conditions most likely played only a minor role in the reaction that occurred after vaccination.

He also said it was a “likely possibility” that the people who developed the clotting disorder had some rare, unknown biological traits — what he called “individual co-factors” — that predisposed their immune systems to make powerful, misdirected antibodies in response to the vaccine. He called that “good news” for the general population, who do not have the co-factors.

There is “clear evidence” that the AstraZeneca vaccine in rare cases leads the body to make antibodies that activate platelets, and that those antibodies are causing blood clots, Dr. Greinacher said.

But, he added: “We have no way to predict who will develop these antibodies.”

So far, his laboratory has identified only about 40 cases, of 1.4 million people in Germany who have received the vaccine. If the vaccine alone were causing the problem, without individual co-factors, there would be many, many more cases, Dr. Greinacher said.

He called the deaths in young people “tragic,” but noted that the numbers were small. “Not vaccinating will bring many, many more people with severe complications than vaccination,” Dr. Greinacher warned.

All of the first 11 patients in his study, as well as 17 others with clots after vaccination whose blood was tested, had the antibodies known to activate platelets.

The antibodies led to a condition called thrombotic thrombocytopenia, which caused both clotting and abnormal bleeding. The researchers suggested naming the newly identified version in these patients “vaccine-induced immune thrombotic thrombocytopenia,” or VITT.

Various theories have been offered by scientists as to what touches off the immune reaction. The AstraZeneca vaccine employs a chimpanzee adenovirus to carry DNA into recipients to spark an immune response against the coronavirus. Laboratory studies have suggested that the chimp virus or the DNA might cause the problem. Some researchers have suggested that bleeding from the injection, mixed with the vaccine, might put platelets in the cross-hairs of the immune system.

Dr. Greinacher called the theories plausible but unproven.

The article described specialized blood tests that can be used to diagnose the disorder, and distinguish it from other, more common clotting problems not related to the vaccine. The research team suggested treatment with a blood product called intravenous immune globulin, which is used to treat various immune disorders. Dr. Greinacher likened the treatment to putting out a fire.

Drugs called anti-coagulants, or blood thinners, can also be administered. But the researchers recommended against prescribing a commonly used one, heparin — because the vaccine-related condition is very similar to a severe reaction that occurs, rarely, in people given heparin.

The second report, from Norway, described five patients, one male and four female health care workers ages 32 to 54, who had clots and bleeding from seven to 10 days after receiving the AstraZeneca vaccine. Four had severe clots in the brain, and three died. Severe headaches were among their early symptoms. Like the German patients, all had high levels of antibodies that could activate platelets.

The team from Norway also recommended treatment with intravenous immune globulin. The researchers said the disorder was rare, but “a new phenomenon with devastating effects for otherwise healthy young adults,” and they suggested that it may be more common than previous studies of the AstraZeneca vaccine had indicated.

On Friday, European regulators also said they were reviewing reports of a few blood clot cases that occurred in people who had received the Johnson and Johnson vaccine. In the United States, federal agencies are investigating reports of a different type of unusual blood disorder involving a precipitous drop in platelets that emerged in a few dozen people who had received either the Pfizer-BioNTech or Moderna vaccines.

Benjamin Mueller and Melissa Eddy contributed.

https://www.nytimes.com/2021/04/09/heal ... e=Homepage

[maestrob]

Angela Merkel gets an AstraZeneca dose.

Chancellor Angela Merkel of Germany received a first dose of the AstraZeneca Covid-19 vaccine on Friday, a show of confidence for the vaccine after weeks of confusion over its use across the European Union.

“I am happy that today I received my first dose of the AstraZeneca vaccine,” Ms. Merkel said in a statement. On Twitter, the message included an image of her vaccination documents, though none of the chancellor rolling up her sleeve as other leaders have done.

Some have criticized Ms. Merkel for not being more public about her inoculation at a time when many Germans are wary of getting a shot, especially of AstraZeneca’s vaccine, which has been hampered by concerns over very rare blood clots and logistical bungling in the European Union.

The vaccine was initially given only to people under 60 in Germany, amid concerns that it had not been tested widely enough on older people. Then it was halted entirely after dozens of mostly young women developed an extremely rare clotting that proved fatal in at least seven cases. Since last week, the AstraZeneca vaccine has been available for Germans 60 and older.

“I thank everyone who has been active in the vaccination campaign — and everyone who gets vaccinated,” Ms. Merkel said. “Vaccination is the key to overcoming this pandemic.”

The chancellor was vaccinated hours after urging Parliament to tweak legislation that would allow her to enforce more stringent national restrictions as the coronavirus continues to spread throughout the country. Germany recorded 25,831 new cases on Friday, and the infection rate has risen to 160 per 100,000 people nationwide, well above the rate of 100 set by Ms. Merkel’s government as manageable.

— Melissa Eddy

https://www.nytimes.com/live/2021/04/16 ... irus-cases

[maestrob]

The E.U. is unlikely to order new AstraZeneca doses, a minister says.

The European Union is unlikely to buy new doses of the AstraZeneca and Johnson & Johnson Covid-19 vaccines, a French minister said on Friday, the first public comment from a government official indicating that the bloc will do without two vaccines it long counted on to move out of the pandemic.

France’s industry minister, Agnès Pannier-Runacher, told RMC radio that although no final decision had been made, “it is highly probable” that no further doses of the vaccines would be ordered.

Several European countries briefly suspended the administration of AstraZeneca vaccine last month before resuming it, recommending use in older age groups only.

“We have not started talks with Johnson & Johnson or with AstraZeneca for a new contract, but we have started talks with Pfizer/BioNTech and Moderna,” Ms. Pannier-Runacher said.

The comment came days after the European Commission, the bloc’s executive arm, said that it was negotiating a contract extension with Pfizer/BioNTech, pivoting away form AstraZeneca’s vaccine on which it had initially bet big.

“We need to focus on technologies that have proven their worth,” Ursula von der Leyen, the Commission’s president, said of the Pfizer/BioNTech vaccine.

On Wednesday, Denmark became the first country to permanently stop the use of AstraZeneca’s vaccine.

https://www.nytimes.com/live/2021/04/16 ... irus-cases

[maestrob]

J.&.J. Vaccine Will Be Available Again Soon

U.S. experts weigh the risks for younger women and cases of a rare blood-clotting disorder, and lift the pause in giving the one-shot vaccine.

By Denise Grady, Julie Bosman and Noah Weiland
April 23, 2021

Use of the one-shot Johnson & Johnson Covid vaccine will resume within days, but with a warning added to its label about the risk for a rare blood-clotting disorder that has occurred among young women, the Food and Drug Administration announced on Friday.

Concerns about the disorder had led to a pause in the use of the vaccine that began 10 days earlier.

The F.D.A. decided against limiting the vaccine’s use by age or gender, although some European countries have imposed such restrictions on a vaccine made by AstraZeneca because of a similar clotting disorder.

Federal health officials said information about the disorder would also be provided at vaccination sites, and Dr. Peter Marks, the F.D.A.’s top vaccine regulator, predicted that the shots could be resumed by Saturday morning.

The company supported adding the warning label and agreed on its language, said Dr. Joanne Waldstreicher, the chief medical officer at Johnson & Johnson. The label notes that “most cases” of the clotting disorder have occurred in women between 18 and 49 years old.

The suspension came after officials learned that six women had developed a severe disorder that led to blood clots in their brains within about two weeks of receiving the vaccine. One died.

The pause was widely considered a blow to national and global vaccination efforts and removed an effective vaccine that many states and countries had counted on to deploy in hard-to-reach places. Unlike the vaccines made by Pfizer-BioNTech and Moderna, Johnson & Johnson’s vaccine requires only one shot and is easier to store and distribute because it does not require extremely cold temperatures.

At an advisory panel meeting about the blood-clotting issue on Friday, the C.D.C. reported that it had identified a total of 15 cases, including three deaths.

But the risk is considered extremely small — nearly eight million Americans have received the Johnson & Johnson vaccine — and the panel decided that the vaccine’s benefits far outweighed its risks. The panel also concluded that failing to use it would lead to more deaths than the clotting disorder might cause.

The panel voted 10 to 4 to resume use of the vaccine with the warning label. Some of the panel members who voted “no” wanted a more prominent warning about the risk to younger women and the availability of other Covid vaccines that do not appear to pose the same risk.

Lifting the pause will allow states to restart vaccination efforts among hard-to-reach populations like rural Americans, migrants and elderly people who have difficulty leaving their homes. Their access to the vaccine had been hampered by the suspension, which left roughly 10 million doses sitting on shelves.

In Wisconsin, officials said they intended to begin using their Johnson & Johnson doses as soon as possible.

“We have also heard from a number of vaccinators who say that there are lots of people who don’t like needles,” said Julie Willems Van Dijk, the deputy secretary of the state health department. “They just want to get the vaccine that requires them to have one shot versus two shots.”

Dr. Rochelle P. Walensky, the C.D.C. director, said governors in a number of states had expressed intense interest in resuming use of the shots.

“They wondered why we had paused, and they were anxious to have this back, have an opportunity for a single-dose vaccine, for a one-and-done possibility,” she said.

About 135.8 million people in the United States have received at least one shot of a coronavirus vaccine. But daily doses have fallen by almost 13 percent since last week, from a peak of 3.38 million daily doses on average to about 2.95 million.

It is difficult to say what is driving the decrease. Even before use of the Johnson & Johnson vaccine was paused, shipments had dipped because of a factory error that had ruined millions of doses.

Larry Bergner, the administrator for the health department in Newton County, Mo., population 58,000, said demand there had been falling before the pause. He was concerned that the federal government’s decision had made even more people in his area hesitant about getting the vaccine.


“Some tell me that they had planned on getting vaccinated until J.&J. was halted,” Mr. Bergner said. “Now, they say they are going to hold off until they feel confident that all vaccines are safe.”

The county had distributed fliers and made phone calls to businesses, churches and other community groups to drum up interest for a vaccination clinic on Wednesday, but only 14 people showed up. It was actually about double what Mr. Bergner had expected, he said, though the health department could have handled about 100 shots.

Dr. Walensky said the federal government planned to emphasize the vaccine’s safety to Americans who might be hesitant to take it after the pause.

“We have to do extraordinary outreach to clinicians, as we have been doing this past week,” she said. “We already have plans to start that on Monday, to public health officials. And then we have to do extraordinary outreach to patients, to meet people where they’re at, to educate them.”

She said the C.D.C. had talked to health providers for young women, including the American College of Obstetricians and Gynecologists. The pause and investigation into the rare clotting disorder, she added, should give the public confidence in the system used to monitor vaccine safety.


European Union regulators earlier this week did not recommend the kind of age restrictions for the Johnson & Johnson shots that some individual countries have imposed on the AstraZeneca vaccine. Johnson & Johnson did agree to include a warning of risks for the blood clots, and several European countries have resumed use of the vaccine, as has South Africa.

Up until just hours before the pause was recommended by American officials, regulators had planned for a revision to the F.D.A.’s emergency use authorization similar to the one formalized Friday, with warnings about the blood clots.

But top health officials decided on April 12 that the government should call for a pause while federal authorities and the C.D.C.’s expert panel investigated a possible link between the clots and the vaccine. They feared a number of cases of the disorder had not been identified and wanted to allow more time for those who had just received the vaccine to reach the point at which the rare clotting typically appears.

“As we did this intensive scientific evaluation over recent days, I think we became more and more confident about the decision that was made today,” Dr. Janet Woodcock, the acting F.D.A. commissioner, said on Friday.

In the C.D.C. panel analysis, women between 30 and 39 appear to be at greatest risk, with 11.8 cases per million doses given. Among women 18 to 49, there have been seven cases per million doses.

The clotting condition, which the C.D.C. is calling thrombosis with thrombocytopenic syndrome, causes severe blood clots and a tendency to bleed at the same time because of abnormally low levels of platelets, a blood component involved in clotting.

The disorder is “rare but clinically serious,” Dr. Tom Shimabukuro, the deputy director of the C.D.C.’s immunization safety office, said at the meeting.

Additional potential cases, including some in men, are being reviewed. A 25-year-old man who participated in a clinical trial of the vaccine also developed the disorder.

Symptoms closely resemble a rare syndrome that can be caused by heparin, a widely used blood thinner, Dr. Michael Streiff, a hematologist at Johns Hopkins University, told the panel. Heparin, typically used to treat blood clots, should not be given to these patients, he said.

The symptoms include severe headaches, abdominal pain, leg pain or shortness of breath. Those problems generally do not set in before about six days after the vaccination. Once the symptoms occur, treatment should begin as soon as possible, because it can worsen rapidly, researchers say.
Dr. Marks, the F.D.A. regulator, said the agency was recommending blood thinners other than heparin and a blood product called intravenous immune globulin, which can help ease the immune reaction causing the problem.

“That appears to reverse this process,” he said.


Researchers suspect that in these rare cases, the vaccine causes an intense reaction by the patient’s immune system, which churns out antibodies that activate platelets, a blood component needed for clotting. Why this occurs in some people is not known, and experts say that they have so far been unable to identify traits or underlying conditions that may make some people susceptible.

Top U.S. health officials have stressed that finding the small number of cases of a rare disorder and pausing use of the vaccine demonstrated that safeguards were in place to assess risks and to raise awareness among doctors and hospitals about the unusual symptoms.

“This pause was essential to our ability to inform the public,” Dr. José R. Romero, chairman of the expert panel, the Advisory Committee on Immunization Practices, said on Friday.

A poll released this week from Ipsos/Axios found that the pause itself boosted confidence in federal vaccine monitors, with 81 percent saying that the C.D.C. and the F.D.A. acted appropriately. The sentiment was unusually bipartisan, with 87 percent of Republicans and 91 percent of Democrats sharing that view.

Measuring the impact of the Johnson & Johnson pause is tricky, said Liz Hamel, vice president of public opinion and research survey at the Kaiser Family Foundation. “You don’t know what the trajectory of the vaccine uptake would have been in the absence of this pause,” she said.

The biggest challenge ahead, she noted, will be the creation of vaccine-confidence messages that resonate with the public. “We don’t know whether it has increased hesitancy among women in particular,” she said.

https://www.nytimes.com/2021/04/23/heal ... e=Homepage