Two weeks after the European Medicines Agency first assured EU member states it had found no link between the Oxford/AstraZeneca vaccine and earlier reports of rare blood clots, a growing number of countries have announced new restrictions on the use of the jab.
While the UK and Austria have imposed no curbs, France, Sweden, Finland, Canada and most recently Germany have recommended that younger people avoid the shot. In Norway and Denmark, it is still suspended.
The EMA, the World Health Organization and the UK’s Medicines and Healthcare products Regulatory Agency all state that the benefits of the vaccine outweigh any possible risks. But a rare combination of blood-related symptoms seen in a small number of people has meant some governments are proceeding with more caution.
The main condition causing alarm is called cerebral venous sinus thrombosis (CVST), when blood forms clots in the veins that run from the brain, a potentially fatal complication. In the cases of concern, this has been combined with something called thrombocytopenia where a patient also presents abnormally low levels of platelets, resulting in heavy bleeding.
In Norway, health officials have reported at least six such cases among 120,000 recipients of the jab, four of whom died. In Germany, 31 cases have been reported after 2.7m vaccinations, including 29 women aged between 20 and 63, and two men aged 36 and 57. Nine of them have died.
The UK regulator on Thursday announced it had identified another 25 cases, taking the number of incidents of the rare condition in Britain to 30 out of a total of 18.1m people who have received the AstraZeneca shot — roughly one in every 600,000 recipients.
One hypothesis, put forward by a team of researchers in Germany, is that the AstraZeneca vaccine could be provoking an overexcited immune response in some people, causing them to generate antibodies that target blood platelets.
The rare combination of blood clots and low platelet counts usually affects roughly three in 100,000 people per year in Germany, according to one of the researchers, who said that the 31 cases identified within two weeks of vaccination with the AstraZeneca vaccine pointed to an incidence rate 10 times higher than normal.
“It’s not just the numbers, it’s also the mechanism — it’s like a puzzle where from different angles there’s evidence that this is something unusual,” said Johannes Oldenburg, professor of transfusion medicine at the University of Bonn, who helped develop the hypothesis. Oldenburg said he believed it was “very likely that these cases originated from the AstraZeneca vaccine”.
If the vaccine is causing this adverse reaction, the different incidence levels in different countries could be a consequence of the different age profiles of those who have received the vaccine, some experts said.
Mainland Europe, for example, has given the AstraZeneca vaccine to more people under the age of 60 than the UK, which vaccinated healthcare workers and older people first, using an even split of Pfizer and AstraZeneca shots.
“It’s a complex problem of different countries using different vaccines, in different age groups and that may explain the differences,” said Saad Shakir, director of the Drug Safety Research Unit in Southampton, which is conducting a study of the AstraZeneca vaccine as it is rolled out across the UK. It was possible, Shakir said, that some younger people with more robust immune systems had experienced rare immune overreactions to the vaccine.
It is also true, experts said, that younger people, and young women in particular, were normally more susceptible to these types of rare blood clots. In the general population, the symptoms are about three times more common in women than men, and the median age of those afflicted is 33.
However, the EMA said on Wednesday that it had still not been able to identify any evidence of a link between the blood clots and specific risk factors “including age, gender or previous history”.
“At the moment, at this stage of our investigations, the link is possible and we cannot say any more than that at this point,” said EMA chief Emer Cooke. “There is no evidence that would support restricting the use of this vaccination in any population.” The MHRA did not disclose the age or gender of the new cases identified in the UK.
The difference in the position of the EMA and some European scientists has led to varied and sometimes conflicting national advice on who should get the shot and who should not.
France and Canada are restricting the vaccine to people over 55
Germany is recommending it only to people over 60
Italy is restricting the jab to people under 80
Austria and the UK have no restrictions in place
Sweden and Finland are using it only for those over 65
In Norway and Denmark the shot is suspended until at least mid-April
Switzerland has still not approved the jab at all
Not many. In the UK, there have been at least two reports of CVST in people that have received the Pfizer vaccine. But the MHRA said on Thursday that those cases had not been combined with the low platelet counts seen among CVST cases in recipients of the AstraZeneca jab. More than 12m doses of the shot have been administered.
Oldenburg, at the University of Bonn, said he was not aware of any reports of similar incidents in people who had received any of the other Covid-19 vaccines being used in Europe, specifically the shots made by Pfizer and Moderna.
One member of the joint committee on vaccination and immunisation (JCVI) that advises the UK government said it would be “premature” to say definitively that the Pfizer shot had not led to similar problems. “[Experts in Europe] have looked more closely at the AstraZeneca vaccine so they’ve found more things,” the committee member said.
Officials in the UK say there is insufficient evidence at the moment to make any changes to the vaccination policy. And even if a causal link were established, some UK-based experts said it would still make sense to continue with vaccinations as the blood clot incidents appeared to be extremely rare.
“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 MHRA said on Thursday, after releasing details of the newly recorded cases of blood clots with low platelet counts.
The JCVI member said: “The UK position is broadly that AstraZeneca and Pfizer are probably safe, or the risks are so small that they are massively outweighed by the benefits, so we should continue to use them.”
It was possible that in the future there could be “a case for modifying their use for younger age groups, but we’re a long way off that,” the person added, describing the European moves as “premature”.
Germany’s Oldenburg said he agreed with the UK’s decision, even though he believed strongly that the AstraZeneca shot was causing the symptoms.
“If I had a choice between immediate vaccination with AstraZeneca or waiting four weeks for Moderna, then I would choose the AstraZeneca vaccine, because the four weeks of protection far outweighs this risk.”
Oxford university and AstraZeneca say their trials show that the vaccine is safe and effective and that they are continuing to monitor for side-effects as the shot is rolled out.