LONDON – Astrazeneca plc’s COVID-19 vaccine is safe and effective and the benefits well outweigh any risks, according to a review carried out by the EMA, following reports of blood clots in people who received the vaccine.

But Emer Cooke, executive director of the EMA, said the investigation has uncovered “a small number of cases of rare and unusual, but very serious clotting disorders” in which it has not been possible to “rule out definitively a link between these cases and the vaccine.”

Investigations will continue into these rare events. In the meantime, the warning on the label will be changed to raise awareness, and a letter will be sent to all medics to alert them to the possible risk. Cooke said she herself would not hesitate to receive the Astrazeneca vaccine, but she would want to be informed about any potential for serious side effects.

Emer Cooke, executive director, EMA

The EMA made its pronouncement just after the U.K. Medicines and Healthcare products Agency reached a similar conclusion, announcing the available evidence does not link use of the Astrazeneca vaccine to venous thrombosis. That followed a detailed review of reports of adverse events, data from hospital admissions and general practitioner records from across the U.K., where to date 11 million doses have been administered.

The MHRA’s conclusion was confirmed by the U.K.’s independent Commission on Human Medicines.

However, in common with the EMA, the MHRA is still reviewing five reports of cerebral venous sinus thrombosis (CVST), a very rare form of thrombosis in the cerebral veins, occurring together with lowered platelet counts. This has been reported in five men aged 19 to 59, of whom one has died.

Like the EMA, the MHRA’s advice remains that the benefits of the vaccines against COVID-19 continue to outweigh any risks and that the public should continue to get their vaccine when invited to do so.

Post-Brexit, the MHRA is outside the EMA network, but the two agencies are cooperating in carrying out their respective safety assessments.

June Raine, MHRA chief executive, said there is no evidence venous thrombosis is occurring more than would be expected in the absence of vaccination. “A link to the vaccine is unproven, [and] the benefits of the vaccine in preventing COVID-19, with its associated risk of hospitalization and death, continue to outweigh the risks of potential side effects,” she said.

As a precautionary measure, anyone with a headache that lasts for more than four days after vaccination, or bruising beyond the site of vaccination after a few days, should seek medical attention, Raine said.

Sabine Straus, chair of the EMA’s safety committee, said the 469 reports of thromboembolic events, including 191 from Europe, seen after vaccination in both clinical trials and after rollout of vaccination campaigns, was lower than that expected in the general population.

Thrombosis is a very common condition, with about 100,000 people per month affected across the EU. “If you vaccinate a large population, you will always encounter certain events,” Straus said.

Countries across Europe, including France, Germany, Italy, Spain, Ireland, Sweden and Denmark, have suspended vaccination with the Astrazeneca product, pending the EMA’s review. That is in the face of rising numbers of COVID-19 cases, with some countries experiencing a fresh wave of infections.

In some countries, certain batches were withdrawn, but the EMA said there is no evidence of a problem related to specific batches of the vaccine, or to particular manufacturing sites.

Cooke refused to be drawn on whether EU member states were right to put vaccinations on hold. “We are very much aware some member states have paused vaccination. But given thousands are dying in the EU, it was crucial for EMA to review all the evidence,” she said.

The EMA’s role is to provide the right evidence so member states can make the correct decisions on use of the vaccine, said Cooke. “We continue to remind ourselves of what a bad situation we are in. We have vaccines that save lives and prevent hospitalization. We need to use these vaccines,” she said.

18 cases of CVST

In total, the EMA looked in detail at 18 cases of CVST, seven reported from Germany, three from Italy, two from Norway, two reports from India and three of the U.K cases. It also investigated seven cases of disseminated intravascular coagulation (DIC). Nine people have died as a result.

Most cases occurred in people under 55 and the majority were women. Because these events are rare, and COVID-19 itself often causes blood-clotting disorders, it is difficult to estimate a background rate for these events in people who have not had the vaccine. Based on pre-COVID-19 figures, the EMA calculated less than one reported case of DIC might have been expected by March 16 among people under 50 within 14 days of receiving the vaccine, whereas five cases were reported.

Similarly, on average 1.35 cases of CVST might have been expected among this age group, whereas by the same cutoff date there had been 12. A similar imbalance was not visible in the older population given the vaccine.

Amongst the further investigations, the EMA will be looking at possible links between serious thrombotic events and oral contraceptives, will conduct lab tests to see if there is anything about individual patients to explain these serious events, and carry out stratified epidemiological studies to look at levels of thrombosis in the different groups that have received the vaccine in different countries.