The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) confirmed on Wednesday 7 April that the cases of thrombosis, accompanied by a low level of blood platelets, are indeed side effects of the Covid-19 vaccine produced by the Anglo-Swedish firm AstraZeneca.
This conclusion—which does not call into question the benefit-risk ratio of the product—had not been completely excluded in the previous analysis conducted by the EMA (see EUROPE 12681/2).
It was established after consultation with an ad hoc group of experts and review of more than 80 cases of blood clots in veins of the brain (cerebral venous sinus thrombosis, CVST) and abdomen (splanchnic vein thrombosis, SVT).
However, these side effects remain “very rare”, EMA Executive Director Emer Cooke, PRAC Chair Sabine Straus and the head of the Methods and Data Analysis Working Group, Peter Arlett, told the press.
As of 4 April 2021, while approximately 34 million people had been vaccinated in the European Economic Area and the UK, 169 cases of CVST and 53 cases of SVT had been reported via EudraVigilance—the EMA’s database of suspected adverse reactions to authorised medicines.
Reported cases
The agency is not currently able to provide incidence rates for these thrombosis cases, but only rates calculated on the number of reported cases, Ms Straus said. “At the moment, the most up to date estimation of CVST is one to two per hundred thousand [vaccinations].
This refers to the ‘reporting rate’. It varies greatly depending on the quality of the reporting system in a Member State and the quality of case identification.
For other vaccines, the damage is less severe: the EMA is currently aware of three cases of CVST linked to the Johnson & Johnson vaccine—following its entry on the market—out of 4.5 million vaccinations, 35 cases out of 54 million vaccinations linked to the Pfizer-BioNTech vaccine, and 5 cases out of 4 million vaccinations with the product developed by Moderna, Ms Straus and Mr Arlett clarified.
A positive benefit-risk ratio
In addition to the rarity of thrombosis cases, the three experts also emphasised the benefit-risk ratio of AstraZeneca’s vaccine, which was once again deemed positive. “The benefits of the AstraZeneca vaccine in preventing Covid-19 outweigh the risks of side effects overall. [...] Covid still causes thousands of deaths in the EU every day. This vaccine has proven to be very effective, preventing serious illness and hospitalisation”, Ms Cooke reiterated, calling on Europeans to use the vaccines available to them to protect themselves from the “devastating effects” of the virus.
As regards the groups most likely to be affected by the observed side effects, the EMA remains very cautious.
“Specific risk factors such as age, gender or medical history of bleeding disorders could not be confirmed”, Ms Cooke acknowledged, explaining that adverse events had been observed in men and women of all ages.
“Most of the cases occurred in people under 60 and in women, but because the vaccine is used differently in different countries, the committee did not conclude that age and gender were clear risk factors for these very rare side effects”, added Ms Straus.
The fact that about 60% of the vaccines were administered to women in the Member States could explain this finding. “But it could also be due to other factors that we have not yet been able to identify”, she added.
States wary, despite everything
Will these conclusions be enough to make the States—France, Germany, the Netherlands, in particular—which have advised against, or even suspended, the vaccination of young people with the AstraZeneca vaccine, reconsider their decision?
On Wednesday afternoon, other Member States followed suit: Estonia suspended the use of the vaccine for people under 60 and Belgium for people under 55. The UK is showing even more caution. The UK government’s immunisation body also said on Wednesday that people under 30 should be given an alternative to the AstraZeneca vaccine.
EU Health Ministers were also invited by the Portuguese Presidency of the EU Council to meet after the EMA press conference to “[share their] national positions regarding the administration of the AstraZeneca vaccine”, in order to “reach a common understanding regarding its place in the European Union’s vaccination efforts”.
However, the ministers were still in discussion at the time of going to press. (Original version in French by Agathe Cherki and Sophie Petitjean)