As trial for children is paused... Oxford jab: What you and your family need to know
Keep on having the AstraZeneca dose, regulator says as it carries out clots review
ScientiStS halted a UK-based trial of the Oxford/AstraZeneca jab in children last night as Britain’s medicines regulator investigated a potential link to rare adult blood clots.
the University of Oxford said it had paused giving the vaccine to new recruits to the trial while it waited for more information on the risks, although it stressed this was a precautionary move.
Boris Johnson yesterday backed the Oxford/ AstraZeneca jab, although Downing Street is braced for the regulator to potentially impose some restrictions on its use as early as today.
Several countries have already limited its use to older age groups in the wake of cases of younger people suffering from rare blood clots after receiving the injection.
the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is yet to decide on the issue, but has said it is conducting a ‘thorough and detailed’ review into reports of ‘very rare and specific types’ of clots. it could announce a decision as early as today but has said that people should continue to be vaccinated.
Both the european Medicines Agency (eMA) and the World Health Organisation are conductin
‘It is clear that there is a link’
ing their own reviews, which are also likely to conclude this week.
Yesterday, an official at the eMA said there appeared to be a ‘clear link’ between the jab and clots.
Mario cavaleri, head of vaccines strategy at the eMA, told italian newspaper il Messaggero: ‘in my opinion, we can say it now, it is clear there is a link with the vaccine. But we still do not know what causes this reaction.
‘We are trying to get a precise picture of what is happening, to define in detail this syndrome due to the vaccine. Among the vaccinated, there are more cases of cerebral thrombosis... among young people than we would expect.’
Last night, Oxford said it was pausing a UK-based trial of the jab children. the trial, which started in February and plans to enrol 300 children aged six to 17 years, will continue in those who have already been dosed. A university spokesman insisted that no safety issues had been identified in the trial itself and that it was awaiting further information from the MHRA before proceeding.
On a visit to an AstraZeneca plant in Macclesfield yesterday. the Prime Minister urged Britons to continue to have covid vaccines when offered, saying that getting everyone inoculated remained ‘key’ to attempts to control the virus. ‘On the Oxford/AstraZeneca vaccine, the best thing people should do is look at what the MHRA say, our independent regulator – that’s why we have them, that’s why they are independent,’ he said. ‘their advice to people is to keep going out there, get your jab, get your second jab.’
the main condition causing concern is cerebral venous sinus thrombosis (cVSt), where potentially fatal clots form in the veins that drain blood from the brain.
this has been combined with what is known as thrombocytopenia, where a patient also has abnormally low levels of platelets – cell fragments in the blood that form clots and stop or prevent bleeding.
the eMA yesterday said its committee examining the issue had ‘not yet reached a conclusion and the review is currently ongoing’. it had previously said there was ‘no evidence’ to support restricting the use of the Oxford/AstraZeneca covid vaccine in any population. However, norway and Denmark have suspended its use completely, France and canada have restricted it to over-55s only and some other countries to the over-60s or over65s. Meanwhile, Dr Rogerio Pinto de Sa Gaspar, director of regulation at the WHO, said there was still no proof of a link. He added: ‘the appraisal that we have for the moment, and this is under consideration by the experts, is that the benefit-risk assessment for the vaccine is still largely positive.’
the MHRA has identified 22 reports of cVSt and eight of other thrombosis events with low platelets out of the 18.1million doses administered in the UK to March 24. there have been seven deaths among the 30 cases. Scientists say the figures suggest the risk of death is the equivalent of around one in a million.
there are normally thought to be around five to 15 cases of cVSt per one million people each year.
the MHRA said the benefits of the vaccine in preventing coronavirus outweigh any risks and it urged the public to continue coming forward for the jab. One option thought to be under consideration in the UK is restricting its use to the over-30s, with younger people given an alternative jab.
However, there are fears that any restrictions imposed by the MHRA would harm confidence in the jab.
As a clinical neurologist, I must balance on a daily basis the risks and benefits of interventions in often complex, high-risk situations.
While these are specialised decisions about the net benefit of a particular course of action, they are the stuff of medicine in general – and of course of life, too.
And it is just such a judgment that is preoccupying the minds of both scientists and the public following the news yesterday that the European Medicines Agency’s head of vaccines Marco Cavaleri now believes there is a ‘clear’ link between AstraZeneca’s Covid vaccine and blood clots.
This follows weeks of reports of unusual blood clots detected in the brains of some of those given the Oxford vaccine – a small number, but enough to lead some countries, including Germany, France and Canada, to restrict who can be given the jab.
Little wonder that the low thrum of anxiety has now grown into more serious concern that could potentially undermine the rollout of the so far hugely successful vaccine programme.
This alarm is understandable, particularly against the backdrop of a year in which the world has been turned upside down.
VACCInE chiefs are treading a fine line between acknowledging concern over the latest worrying headlines and keeping us focused on the benefits of a vaccine they see as the best chance of freeing us from a virus with its own proven catastrophic consequences, among them – ironically – the chance of developing potentially fatal blood clots, symptoms affecting around one in four who contract severe Covid-19. Of course, blood clots are not always inherently bad: indeed, we would be in a great deal of trouble without them.
Comprised of platelets, red blood cells and a mesh-like protein called fibrin, their usual function is to prevent bleeding by helping to seal off a wound. The problems we associate with blood clots occur when one forms in a blood vessel when it shouldn’t, leading to all kinds of potentially serious and sometimes fatal health conditions.
In our arteries – vessels that carry blood away from the heart into vital organs – they cause heart attacks and strokes.
In our venous system (the vessels that carry slower moving deoxygenated blood usually back to the heart), the most common problems are deep vein thrombosis from a clot in the leg, and pulmonary embolism from a clot in vessels carrying deoxygenated blood to the lungs.
In my work I sometimes see a rare type of stroke caused by a clot in veins that drain blood from the brain, a condition known as cerebral venous sinus thrombosis (CVsT). It is this latter kind that has been reported in a small number – around 30 – of the estimated 18million Britons who had received the Oxford vaccine by March 24. The great majority of these vaccine-associated CVsTs have been in young females, and, worryingly, there has been a high rate of fatality.
We don’t have the data to explain why women have been disproportionately affected yet but, in cases of CVsT not connected to vaccines, about twothirds involve females, which can probably be attributed to associations with the contraceptive pill and pregnancy.
Like many doctors, my first instinct was that, given the low number of reports, it could be nothing more than coincidence.
However, distinctive features have emerged in the reported cases which have generated concern about a link to the vaccine, not least that patients had low levels of blood platelets and unusual anti-Platelet Factor 4 antibodies, suggesting an immune reaction. These antibodies are usually found in people who have been given the blood thinner Heparin and gone on to develop something called Heparininduced thrombocytopenia, a condition in which platelets are reduced but blood clots are more likely to form.
It raises the question of whether the vaccine triggered an immune response which included the production of these antibodies and a related, heightened chance of clotting. Yet it’s also important to state here that an association is not the same thing as a direct causal link, for which researchers need a great deal of complex supporting evidence.
There is also much we don’t know about these reported cases in terms of any shared characteristics among those involved. More research is needed before we can definitively say that all of the reported brain blood clots were caused by the AstraZeneca jab.
THE fact remains that all vaccines have the potential to harm a small number and that harm has to be weighed against the clear overall benefit for the majority of the population.
As things stand, the risk of a blood-clotting problem is vanishingly small, about one in 600,000, though – it has to be said – we are in a rapidly evolving situation. Ongoing research and close surveillance is vital. It may be that a causal link is established between the Oxford jab and these brain blood clots, and, if so, it is important that doctors are made aware so that they can offer rapid diagnosis and specific treatments.
Indeed, I understand that the World Health Organisation, the EMA and our own Medicines and Healthcare products Regulatory Agency may clarify their policies over the AstraZeneca vaccine as early as today and we must, of course, follow their advice.
But whatever conclusion they arrive at we must not allow it to detract from our appreciation of the great success of our vaccination programme to date.
n David Werring is Professor of Clinical Neurology at the UCL Queen Square Institute of Neurology.