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Adults under 30 years of age will be offered an alternative vaccine to the AstraZeneca/Oxford vaccine as a preference and where this is available, according to Professor Jonathan Van-Tam, England’s deputy chief medical officer, speaking at today’s update by the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA).
The agency notes that the balance of benefits over risk favored use of the Astra Zeneca/Oxford vaccine overall, but concludes a possible link between the AstraZeneca vaccine and extremely rare, unlikely-to-occur blood clots.
“This is a vanishingly rare but sadly very serious adverse event,” Van-Tam acknowledged. “But this is a ‘course correction’ in the UK vaccine program. If you said to me [last March] that we wouldn’t need a course correction I would have been surprised,” he remarked.
He compared the vaccine roll-out to a “massive beast that we are driving along with enormous pace and with enormous success.”
“If you sail a massive liner across the Atlantic, then it isn’t reasonable that you aren’t going to make at least one course correction during that voyage. It is full speed ahead with the UK vaccine program.”
Andrew Pollard, MD, professor of pediatric infection and immunity, who led development of the vaccine at University of Oxford, said that the identification of rare cases of blood clots, which might be associated with the vaccine, “shows that the safety system works, and has also allowed MHRA and [the European Medicines Agency (EMA)] to conclude that the benefits of vaccination continue to outweigh the risks, while putting in measures to help mitigate any possible risk.”
Total 20.2 Million Doses of AZ Vaccine in the UK
By the end of March, 20.2 million doses of the AstraZeneca/Oxford vaccine had been given in the United Kingdom, meaning that the overall risk for these blood clots is approximately four people in a million people vaccinated with the AstraZeneca/Oxford vaccine. The MHRA have received 79 reports of blood clots accompanied by low blood platelet count from people aged 18-79 years who had received their first dose only, the agency noted in a press statement.
Of these, 51 were women and 28 men. However, Professor Sir Munir Pirmohamed, Chair of the Commission on Human Medicines, also speaking at the briefing, cautioned that, “This may reflect who has been given the vaccine because many healthcare workers are women. If you look at incidence rates, then there is no difference between men and women. We will continue to monitor to see if here is a gender predilection to developing this adverse event. Right now, we cannot say that either men or women are more likely to experience this.”
There were 19 deaths out of the 79 case reports, three of whom were under the age of 30. And out of those deaths, 14 cases involved cerebral venous sinus thrombosis, and five cases were other kinds of thrombosis in major veins.
“There is a slight gradation towards serious adverse events in younger people compared to older, but it is really the benefit-risk balance that is most important here,” said Professor Wei Shen Lim, chair of the Joint Committee on Vaccination and Immunisation (JCVI), also at the briefing. “The benefit in older people is really high and reduces in the younger because the risk of COVID-19 decreases with age, but there is still a benefit to younger people of vaccination.”
“Also, we are not advising a stop to vaccination to any individual in any age group. We advise a preference for one vaccine over another in a particular age group really out of the utmost caution not because we have any serious safety concerns,” Wei Shen Lim said.
Ian Douglas, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, welcomed that the vaccine safety monitoring systems throughout Europe were operating at such speed, with great rigor and transparency. “The evidence from the case reports seems to be compelling enough to conclude at least a possible causal link between the AZ vaccine and rare clots accompanied by low platelet counts. Though I note the caution expressed here; it is still not proven beyond doubt.”
He highlighted that the move to other vaccines in the under-30s needed to be cautious too. “We need to remember this doesn’t mean other vaccines are not also associated with rare clots, just that we have less evidence and experience with them at the moment.”
He pointed out that due to the volume of vaccines being rolled out, “we will continue to find out more about these rare clots and we may well see new safety signals with any of the vaccines…rarer side effects only emerge when we use them at large scale.”
EMA: List Unusual Clots as Rare Side Effects
EMA also made an announcement today of its review of the rare blood clotting events. They said, “unusual blood clots with low blood platelets should be listed as very rare side effects.” EMA executive director Emer Cooke said the review also confirmed that “the benefits of the AstraZeneca vaccine in preventing COVID-19 overall outweigh the risks of side effects.”
The World Health Organization commented on the announcements, pointing out that, based on current information, “a causal relationship between the vaccine and the occurrence of blood clots with low platelets is considered plausible but is not confirmed.” They added that further specialized studies were needed.
They also offered advice on spotting and managing vaccine side effects, notably that those with severe symptoms — such as shortness of breath, chest pain, leg swelling, persistent abdominal pain, neurological symptoms, such as severe and persistent headaches or blurred vision, tiny blood spots under the skin beyond the site of the injection — from around 4 to 20 days following vaccination, should seek urgent medical attention.
Clinicians should be aware of relevant case definitions and clinical guidance for patients presenting with thrombosis and thrombocytopenia following COVID-19 vaccination. They suggest that a committee of clinical experts including hematologists and other specialists be convened for advice on clinical diagnosis and case management.
British Medical Association Council Chair Chaand Nagpaul, MD, commented on the findings from the United Kingdom and European regulators. “It is absolutely right that the JCVI is being honest about the change of direction in advising those who are under 30 to be vaccinated with either the Moderna or Pfizer vaccine.”
“We acknowledge the fact that the risk of blood clots remains an extremely rare event…. We are grateful that our patients can be offered the vaccine that is most appropriate to their age group.”
The JCVI reviews the data entirely independently of any other agencies or reviewing bodies. Lim outlined the JCVI’s conclusion of a review of safety evidence from Public Health England and EMA.
He gave three pieces of advice: healthcare professionals and the public being offered vaccinations should be updated and should reflect the latest considerations by JVCI and MHRA; those who have had the first dose of the AstraZeneca/Oxford vaccine should continue to be offered the second dose according to the set schedule; and adults aged 18 to 29 years without underlying health conditions that place them at higher risk for COVID-19 should be offered an alternative vaccine in preference to the AstraZeneca/Oxford vaccine, if available.
Asked about the mechanisms that might be causing the apparent link between the vaccine and the rare blood clots, Pirmohamed said, “Early evidence suggests that this constellation of symptoms is caused by an immune response against platelets that leads them to cause clotting in different parts of the body. What we don’t have clearly, is the link between the vaccine and the activation of the immune response against the platelets and that is where further scientific work needs to go on.”
He noted that it is very important to understand these mechanisms because in the future it will help to refine the advice given around risk factors, for example. “It might help us modify vaccines to avoid this adverse event.”
Due to supply issues with the AstraZeneca/Oxford vaccine, the United Kingdom has already started rolling out the Moderna vaccine, with first dose given today.
Updated information for healthcare professionals and the public will be provided on how to minimize risks, as well as further advice on symptoms for vaccine recipients to look out for if they persist for 4 or more days after vaccination.