Dual announcements from regulators in the EU and the UK have jointly concluded that the Oxford–AstraZeneca vaccine, now trademarked as Vaxzevria, is effective at preventing COVID-19 and, overall, has benefits that outweigh any risk posed by extremely rare clotting disorders linked to the vaccine.
The findings, both covered by press conferences, slightly differed on the question of whether the vaccine directly caused the clotting disorders. The European Medicines Agency (EMA) said European data was strong enough to formally list the disorders, which include cerebral venous sinus thrombosis (CVST) and other clots in major veins paired with low levels of platelets, as a side effect of Vaxzevria, while the UK Medicines and Healthcare products Regulatory Agency (MHRA) said such a causal link was only “possible” based on current data.
Overall, the data pointed to a risk of a severe clotting event post vaccination as being roughly one in 250,000. The risk of death is roughly one in a million, which is comparable to the risk of death during a 250-mile road trip.
Whilst the MHRA said its data pointed to a higher risk of clotting disorders among younger people, the EMA said that its data could not yet support age or sex as a risk factor. This uncertainty reflects the extreme rarity of these disorders: the EMA’s data totaled 169 cases of CVST and 53 cases of clotting in other major veins among 34 million vaccinations, while the MHRA considered 79 cases of clotting disorders, with 19 deaths, among 20.2 million vaccinations. While more cases were noted in the UK data among women, the regulator said that this higher rate could be due to more women having been vaccinated with Vaxzevria than men.
The regulatory advice caps weeks of deliberation on the origin of the rare disorders, which have seen Vaxzevria restricted to patients over 55 years in France and Belgium and over 60 years in other European countries, decisions made by individual countries’ regulators. The MHRA’s announcement was followed by a recommendation from the UK expert joint committee on vaccines and immunization (JCVI) who suggested that an alternative to Vaxzevria be offered where possible to those under 30 years.
JCVI deputy chair Professor Anthony Harden further explained their decision: “Although the chance of any person receiving the vaccine experiencing a blood clot with low platelets is extremely small, because the risk of severe Covid in the under 30s with no underlying illness is also small JCVI feel as a precautionary measure it is appropriate for those in this age group to be offered an alternative Covid vaccine when their turn comes for their first dose of a vaccine.”
Figure 1: title. Source: MHRA
A graph (Figure 1) shared during the MHRA’s press conference highlighted the difficulties of assessing the risk of such rare side effects. At all age groups above 20–29 years, the risk posed by COVID-19 meant that the benefits of vaccination outweighed any potential harms realized through the risk of any vaccine side effects. But because the virus has been suppressed to a low level in the UK, and because younger people have an extremely small risk of death from COVID-19, the scales fractionally tip away from recommending Vaxzevria for the youngest cohorts currently being vaccinated. This balance would once again change if the virus started circulating widely – at numbers similar to the peak of the UK second COVID-19 wave, viral infection would be six times as risky as any rare vaccine side effect (Figure 2).
Figure 2: title. Source: MHRA
Both boards suggested that further work would immediately begin towards teasing out the mechanisms behind the clotting disorders. In their detailed analysis, the EMA proposed several potential causes, including a heparin-induced thrombocytopenia-like syndrome, a complication from the use of an adenovirus vector or as a result of COVID-19 infection itself, although each theory will need to be further explored in additional research.
The announcements also contained signs to look out for post-vaccination that may indicate clotting side effects. These were:
- shortness of breath
- chest pain
- swelling in your leg
- persistent abdominal (belly) pain
- neurological symptoms, including severe and persistent headaches or blurred vision
- tiny blood spots under the skin beyond the site of injection
The regulators advised that patients should seek medical assistance if they notice any of these symptoms.