European drug regulators have confirmed a link between the Oxford-AstraZeneca Covid-19 shot and rare blood clots, as UK authorities recommended that people under 30 should take alternative vaccines.
The European Medicines Agency (EMA) said Wednesday that a particular combination of unusual blood clots with low blood platelet counts should be listed as a side effect of the vaccine, but stopped short of recommending its use be limited. The benefits of the shot outweigh the risks and Covid-19 is a “very serious disease,” it added.
UK regulators took a more cautious approach, saying healthy adults under 30 should be offered other vaccines. Officials described the move as a “course correction” that would not derail the country’s rapid inoculation program.
The findings could have enormous implications for developing and middle-income countries, many of which are accessing the AstraZeneca shot through Covax, a vaccine-sharing scheme.
EMA officials said they looked at 18 deaths in their analysis. These fatalities were reported in 62 cases of clotting in the sinuses that drain blood from the brain, and 24 cases of clotting in the abdomen. The cases were reported in an EU safety database from European countries, including the UK, where around 25 million people in total had received the AstraZeneca vaccine.
“First of all, I want to start by stating that our safety committee (the Pharmacovigilance and Risk Assessment Committee or PRAC) … has confirmed that the benefits of the AstraZeneca vaccine in preventing Covid-19 overall outweigh the risks of side effects,” EMA Executive Director Emer Cooke told a press conference.
PRAC chair Sabine Straus reiterated the cases of severe clotting with low blood platelet counts were extremely rare but conceded, when challenged by journalists, that EMA did not have the data to understand the extent to which benefits might still outweigh risks for particular groups, by age or sex, for example.
“At the moment that’s something that’s very difficult to answer because the clinical trials … we do not have all the age stratified data available,” said Straus, adding that the agency planned to obtain that data and undertake further analysis.
Cooke said there was no clear risk profile found when the safety committee looked at the age and sex of people reporting these rare adverse reactions, even though a statement published by EMA earlier made clear most of the cases reported “occurred in women under 60 years of age within 2 weeks of vaccination.”
EMA’s statement called on healthcare workers and people receiving the vaccine “to remain aware of the possibility of very rare cases of blood clots combined with low levels of blood platelets occurring within 2 weeks of vaccination.”
UK authorities also concluded the benefits outweighed the risks in most age groups, but presented data that showed the benefits to people under 30 only slightly outweighed the risks in scenarios where exposure to the virus is limited. Those who had already received the first AstraZeneca shot, however, should be offered the second, they said.
EMA’s findings and the UK’s new advice also follow a move in Germany, which last week suspended the use of the AstraZeneca vaccine in people under 60 years old after 31 reports of CVST. Twenty-nine of the 31 were women aged 20 to 63, and nine of the patients died, according to a Reuters report citing the country’s medicines regulator.
After reviewing the data from EMA and the UK, the World Health Organization said in a statement Wednesday 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. Specialised studies are needed to fully understand the potential relationship between vaccination and possible risk factors.”
What does the data say?
The UK’s deputy chief medical officer, Jonathan Van-Tam, presented charts Wednesday showing the balance of risks and benefits for each age group in getting the AstraZeneca vaccine in the UK.
It showed the vaccine offered only slightly higher benefits than risks for people under 30, in scenarios where people are not very exposed — such as those working from home. The analysis considered the likelihood of being admitted to intensive care as its main metric.
People who are around the limit of the age recommendation should make “their own decision” about whether to accept an AstraZeneca vaccine, said the chair of the UK’s Joint Committee on Vaccination and Immunization, Wei Shen Lim.
“For somebody who’s 31 and 32, I think they have to make their own decision as to what they want to do about vaccination,” he said. “We would still say that the balance is in favor of being vaccinated because of the risks from Covid-19 and the protection that the vaccine offers.”
Oxford University said Wednesday that the “the identification of rare cases of blood clots, which might be associated with the vaccine, shows that the safety system works.”
“Safety has been our priority throughout the development of the vaccine at University of Oxford in 2020, and we are reassured to see that safety monitoring continues under the close scrutiny of regulators and public health authorities as the vaccine is rolled out around the world,” Andrew Pollard, Professor of Paediatric Infection and Immunity, said in a statement.
AstraZeneca said Wednesday that it was “collaborating with regulators” to update its product information regarding possible side effects following the announcements by British and European regulators.
“Updates to the UK and EU labels for the vaccine have been requested by the regulators. Neither agency identified any risk factors, such as age or gender, or a definite cause for these extremely rare events. However, they came to the view that these events have a possible link to the vaccine and requested they be listed as an extremely rare potential side effect,” it said.
“Overall, both of these reviews reaffirmed the vaccine offers a high-level of protection against all severities of COVID-19 and that these benefits continue to far outweigh the risks,” the statement added.
Safety concerns around the vaccine is the latest headache for drug company AstraZeneca, which has been at the center of a public war of words between the European Union and UK as it has fallen tens of millions of doses short on its delivery targets to the EU, while appearing to make good on its supplies to the UK.
The company has also come under the scrutiny of drug regulators, including the US Food and Drug Authority, for presenting outdated clinical trial data and, earlier, for mixing data from separate trials that were conducted differently.