The Covid-19 vaccine candidate developed by the University of Oxford and Anglo-Swedish pharmaceutical company AstraZeneca was one of the first vaccine candidates approved for public use. Developed using a weakened version of the adenovirus from monkeys known as ChAdOx1, the vaccine has efficacy levels of 76% after a first dose, rising to 82% when a 12-week interval is left between doses. Since its creation and approval, the vaccine has been the subject of several disputes over its supply to the European Union. Researchers have also found evidence of blood clotting as a very rare side-effect of the first vaccine dose. This has led health authorities in the UK to recommend people under the age of 40 receive an alternative vaccine if available. Authorities in other countries, including Germany, have approved the vaccine for all ages.
Contract dispute with the European Union
AstraZeneca is involved in an ongoing legal dispute with the European Union over supply of its Covid-19 vaccine. The European Commission argues that the bloc only received 30 million jabs in the first three months of 2021, rather than the 90 million it claims AstraZeneca was legally obliged to supply. It argues that while the drug company has met its manufacturing commitments to the UK, it has not done so for the EU.
In the summer of 2020, AstraZeneca signed separate contracts with both the EU and the UK to supply its Covid-19 vaccine. The UK contract was signed three months before the contract with the EU. When initial supply did not meet that specified in the EU contract, partly because of slow manufacturing within European plants, the bloc argued that it had the legal right to supplies from plants based in the UK to make- up the shortfall.
Some legal and medical commentators have argued that the core of the dispute lies in the wording of the initial contract between the EU and AstraZeneca. They have argued that uncertainty over whether the EU can expect supply from UK plants lies in specific contradictory clauses. Clause 5.1 in the EU contract states:
AstraZeneca shall use its best reasonable efforts to manufacture the initial Europe doses within the EU for distribution, and to deliver to the distribution hubs, following EU marketing authorization…
Legal experts have then pointed to clause 5.4, which covers manufacturing sites. This states:
AstraZeneca shall use its best reasonable efforts to manufacture the vaccine at sites located within the EU (which for the purposes of this Section 5.4 only shall include the United Kingdom).
This may have created a legal dispute over what obligations British plants have to supply doses to the EU.
Others have argued that cultural differences between English and Belgian law may be a significant factor in the dispute. The EU contract is written under Belgian law. This includes a concept known as ‘good faith and fair dealing’. This is a complicated legal aspect of the Belgium Civil Code that does not exist in English law. Some have argued that this legal difference allowed the British contract to include more stringent ‘punishment’ terms on AstraZeneca should it fail to deliver on the agreed number of doses.
Is there a risk of blood clots?
On 7 April 2021, the European Medicines Agency (EMA) safety committee listed unusual blood clots with low blood platelets as a very rare side-effect of the Oxford/AstraZeneca Covid-19 vaccine. The majority of the clotting cases occurred in women under 60 within two weeks of receiving the first dose of vaccination. The committee called on health professionals to be vigilant of possible symptoms of clotting, including shortness of breath, chest pain and swelling of the legs. However, the committee concluded:
the reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing Covid-19 outweigh the risks of side effects.
On 31 March 2021, the UK Medicines and Healthcare Regulatory Agency (MHRA) estimated that out of 20.2 million doses then administered, four per million were at risk of blood clots. By 28 April 2021, the MHRA was reporting 242 cases of blood clotting following the first dose of the Oxford/AstraZeneca vaccine. This amounted to 10.5 cases per million doses.
In May, the British Medical Journal (BMJ) published results from a large cohort study looking at the link between blood clots and the Oxford/AstraZeneca vaccine. In this study, conducted on adults in Denmark and Norway who had received the vaccine, seven cases of cerebral venous thrombosis (a potentially life-threatening blood clot on the brain) were recorded. Overall, 281,264 vaccinated participants were studied. This was, the researchers state, around 2.5 extra cases of cerebral venous thrombosis amongst vaccinated participants than would normally be expected per 100,000 people.
The BMJ has provided several caveats and complicating factors to both the study and wider reporting of blood clots as a side-effect. These include:
- heightened awareness and greater reporting of blood clots as a result of greater coverage compared to pre-pandemic levels;
- differences between unvaccinated and vaccinated cohorts making direct comparison difficult; and
- Covid-19 itself being associated with higher risks of cerebral venous thrombosis, regardless of vaccination status.
Like the EMA, the BMJ concludes that the benefits of the Oxford/AstraZeneca vaccine far outweigh the risks. Studying the risks posed by the Oxford/AstraZeneca vaccine compared to other available Covid‑19 vaccines remains a “research and public health priority”.
Guidance for the under-40s
The Joint Committee on Vaccination and Immunisation (JCVI) recommended in April 2021 that those under the age of 30 without underlying health conditions that put them at higher risk of Covid-19 should be offered an alternative to the Oxford/AstraZeneca vaccine, if available. On 7 May 2021, the JCVI published new guidelines increasing the age to those under 40 without underlying conditions.
The balance of risks is an important factor when considering the JCVI’s recommendations. People under 40 with no underlying health conditions are at significantly lower risk from Covid-19 than older groups. This is increasingly true as the overall rate of Covid-19 infection in the UK falls. The evidence emerging around blood clots in the Oxford/AstraZeneca vaccine suggests younger people are marginally more at risk from this rare complication. Other vaccines with no apparent risk of blood clots, such as the Pfizer/BioNTech and the Moderna vaccines, are widely available. This combination of factors has led to the JCVI’s recommendation.
In Germany, where the Covid-19 infection rate is currently higher than in the UK, and where fewer people have received their first dose, health authorities have recently approved the AstraZeneca vaccine for all age groups. This is a departure from previous policies. Initially, German health authorities recommended that the jab should not be given to those over 65. This policy was later scrapped as evidence emerged that the jab was equally effective in the older population. Following concerns over blood clots, the German government suspended the routine use of the AstraZeneca vaccine for people under the age of 60.
In the UK, the JCVI has emphasised that the benefits of prompt vaccination with the Oxford/AstraZeneca Covid-19 vaccine far outweigh the risk of adverse events for the majority of individuals. When the recommended age below which alternative vaccinations should be sought was increased from 30 to 40, the Government said:
The Oxford/AstraZeneca vaccine is safe, effective and has already saved thousands of lives in the UK and around the world.
More than 50 million vaccines overall have already been administered, and our current vaccine supply and rate of infection means we are able to take this precautionary step while remaining on track to achieve our target of offering a vaccine to all adults by the end of July.
Everybody who has already had a first dose of the Oxford/AstraZeneca vaccine should receive a second dose of the same jab, irrespective of age, except for the very small number of people who experienced blood clots with low platelet counts following their first vaccination.
When people are called forward, they should get their jab.
Cover image by Joshua Hoehne from Unsplash.