Medicines regulators in the EU and UK have said that the Oxford-AstraZeneca vaccine appears to be linked to rare blood clotting disorders reported in some people who have received the jab.
The cases of concern centre around an extremely rare condition called cerebral venous sinus thrombosis (CVST), when blood clots in the veins that run from the brain, sometimes culminating in death.
This clotting has been combined with thrombocytopenia, where a patient presents abnormally low levels of platelets.
Of the 54 millions doses administered across Europe and the UK to date, fewer than 300 of these cases have been detected. A higher rate of incidence appears to have been recorded among young women – though adults as old as 79 have been affected.
Both the Medicines and Healthcare products Regulatory Agency and European Medicines Agency have said the vaccine remains safe to use, and that its benefit in providing protection against Covid-19 far outweighs all risks.
What’s the latest in the UK?
Following an investigation into the CVST reports, young people under the age of 30 in the UK will now be offered an alternative to the Oxford-AstraZeneca vaccine.
The government’s Joint Committee on Vaccination and Immunisation has said that healthy adults aged between 18 and 29-years-old, who have no underlying health conditions or risks from coronavirus, should be offered a different jab, where available.
Currently, the Pfizer/BioNTech and Moderna jabs are the only other vaccines that have been licensed.
The MHRA said there had been 79 cases of CVST associated with low platelet cells in the blood. These conditions emerged after administration of the first dose.
Nineteen people have died as a result of the clotting disorders, three of whom were aged under 30, the MHRA added.
The affected patients were all aged between 18 and 79, and included 51 women and 28 men.
Health officials say the AstraZeneca vaccine remains safe for the vast majority of patients, with 20 million doses so far administered across the UK. From this group, an estimated 6,000 lives have been saved, based on the average death rate from Covid.
A UK trial of the Oxford-AstraZeneca vaccine in children has been also paused while regulators at the MHRA continue to investigate a potential association between the jab and CVST.
Oxford University said “there are no safety concerns in the paediatric clinical trial” and that the tests had been paused to await additional information from the MHRA of clots in reported adults.
It made clear that no problems had arisen within the trial itself. Researchers added that parents and children should continue to attend all scheduled visits “and can contact the trial sites if they have any questions”.
What action has Europe taken?
Like the MHRA, the EMA has concluded that the vaccine appears to be linked to the rare clotting disorders, but remains safe to use and should continue to be administered in adults.
A review by the EMA’s safety committee recommended that “unusual blood clots with low blood platelets should be listed as very rare side effects” of the vaccine.
However, the agency said the benefits of the vaccine in providing protection against Covid-19 far outweigh its associated risk. “The risk of mortality from Covid is much greater than the risk of mortality from these side effects,” said Emer Cooke, director of the EMA.
Most of the rare blood clots reported to date have occurred in women under 60 within two weeks of vaccination – but based on the currently available evidence, the EMA said it was unable to identify specific risk factors.
As of 4 April, 169 cases of CVST had been reported out of 34 million doses administered across Europe, the EMA said.
Unlike the UK’s medicines regulator, the EMA has placed no new age restrictions on the jab. Nor has it recommended against administering different vaccines for younger age groups.
Safety concerns surrounding the vaccine have already prompted more than a dozen countries in recent weeks to suspend use of the jab, or restrict its use to certain groups.
Germany has limited use of the jab to people aged 60 and above, as well as high-priority individuals. This comes after the country’s medicines regulator reported 31 cases of CVST among the nearly 2.7 million people who have so far received the jab.
Nine of the 31 people suffering clots died, and all but two of the cases involved women who were aged 20 to 63, Germany’s Paul Ehrlich Institute said. The two men were aged 36 and 57.
France approved resumed use of the vaccine on 19 March, following earlier concerns over blood clotting, but said the jab should be given to people aged 55 and over.
Spain said on 30 March it would use the vaccine for people aged 55-65, and a day later said it would extend the vaccination to essential workers aged over 65.
What could be causing the clotting?
At this stage, no one has a clear answer. Researchers in Germany have speculated that the vaccine could be provoking an overexcited immune response in some people, causing them to generate antibodies that target blood platelets.
The EMA said the side-effect is similar to a thromboembolic condition suffered by patients treated with a blood-thinning medicine called heparin.
Most of the recipients of the AstraZeneca vaccine who developed blood clots also tested positive for an antibody seen in patients who have an adverse reaction to heparin.
Beverley Hunt, professor of thrombosis and haemostasis at King’s College London, said tests had been carried out to find the antibody to a molecule called platelet factor 4.
“We were surprised to find, and it was first found in Germany, that these patients have this positive test for antiplatelet factor 4 antibody,” said Prof Hunt.
“And in many ways they behave like this very rare syndrome of heparin-induced thrombosis.”
What are the symptoms to look out for?
Symptoms associated with the blood clots include shortness of breath, chest pain, swelling in the leg, persistent abdominal pain, severe headaches, blurred vision and tiny blood spots under the skin beyond the area where the injection was administered.
The MHRA has that anyone who has symptoms four days after vaccination should come forward for immediate medical advice.
What have the scientists said?
Professor Adam Finn, a member of the Joint Committee on Vaccination and Immunisation, said it was vital to keep using the AstraZeneca vaccine as society opens up, in order to help stave off rising infection rates.
The “risk-benefit is very strongly in favour of receiving the vaccine,” he told BBC Breakfast – though he insisted the reports were being investigated “very seriously”.
“As time goes forward, we will have much more flexibility about who can be offered what,” he added.
“We are seeing another vaccine coming in (Moderna), and further vaccines are approaching licensure, and I know that the UK has made contracts for quite a wide range of different vaccines.”
Dr Maggie Wearmouth, another member of the JCVI, told the Daily Telegraph that “perhaps slowing things down” with the rollout “until we’re absolutely certain” might be wise.
“The issue is about safety and public confidence,” she said. “We don’t want to cover anything up that we feel that the public should be knowing.
“We’re not here to blindly follow targets or due dates. We will do what is necessary.”
Professor Calum Semple, a member of the government’s Scientific Advisory Group for Emergencies (Sage), said he was “not worried one little bit” about headlines around the AstraZeneca vaccine.
“I’ll take [it] myself, I’m 53, my risk of death from Covid is about one in 13,000, for me it’s a no-brainer, I need to have the vaccine,” he told LBC Radio.
“This vaccine is safe. What do I mean by safe? You can look right, look left, look right again, cross a road, it’s safe to cross because you don’t see any cars (but) you can trip, you can stumble.
“Nothing is risk-free, but is the vaccine safe? I would say yes.”
Last week, chief medical officer Chris Whitty said it was “unproven” if the vaccine was causing the blood clots, but urged the public to “keep an open mind and assume they may well be until it’s actually proven otherwise”.
For anybody who has a significant risk of getting Covid, such as the elderly and those with comorbidities, the “risk benefit is wildly in favour of vaccination”, he added.
“The closer you get to someone who’s right down at 20 and otherwise blameless in their health, the more you have to think through these really very rare side-effects, the risk benefits might get closer to parity.”
Dr Peter Arlett, head of data analytics at the EMA, said that oral contraceptives gave a “benchmark” of another medicine given to a healthy population that has rare side effects, pointing to the example of the contraceptive pill.
“These are given to women who are normally otherwise healthy, although obviously in a big population some of those women will have other risk factors and other conditions,” he said. “And if we treat 10,000 women with a combined hormonal contraceptive for a year, we will see four excess blood clots in that year.”