The AstraZeneca vaccine – should you be worried?

Earlier this week, the European Commission announced that the Covid-19 vaccine, developed as part of a collaboration between the British pharma company AstraZeneca and University of Oxford, is no longer authorised for use, after the company made the decision to remove it from the market.

The news follows a high-profile court case in which AstraZeneca was sued by more than 50 alleged victims and grieving relatives, relating to serious injuries or death due to a very rare side effect which occurred during the vaccine rollout.

Overall, the jab has been linked to at least 81 fatalities and hundreds of injuries in the UK, and Dr Michael Head, a global health researcher at the University of Southampton, says that more should have been done to make it easier for those who suffered vaccine-related harm, to receive compensation.

“The public sign up for a vaccine campaign in good faith,” says Dr Head. “If there are adverse events, then those who were injured by vaccines are entitled to compensation. And I suspect that those compensation mechanisms are harder to access than they should be.”

It is now almost three and a half years from when the vaccine was first approved for use in the UK in December 2020. While it is widely acknowledged to have played a major role in curbing the vast numbers of hospitalisations and fatalities from Covid-19, there remain ongoing questions as to why it seems to have led to sudden death or permanent injury in a small minority of people.

How did the AstraZeneca vaccine work and how was it different to Pfizer’s vaccine?

As Peter Openshaw, a professor of experimental medicine at Imperial College London points out, AstraZeneca is not traditionally a vaccine company. Instead, AstraZeneca is better known for producing drugs to treat cancer, cardiovascular diseases, and rare diseases.

During the first year of the pandemic, the company formed a collaboration with vaccine experts at the University of Oxford who had been developing a vaccine platform based on adenoviruses, common viruses which typically cause cold or flu-like symptoms. This technology had already been studied for many years as a means of developing vaccines against other coronaviruses such as SARS and MERS, which had previously caused epidemics, as well as deadly viruses such as Ebola, Zika and HIV.

While the Covid vaccines developed by Pfizer and Moderna carried strands of artificial messenger RNA, molecules designed to instruct immune cells to recognise and attack a virus, the Oxford/AstraZeneca vaccine achieved the same results via a subtly different mechanism. The injection inserted an adenovirus – carefully modified so that it could not replicate inside human cells – which was carrying the SARS-CoV-2 spike protein gene. When this adenovirus bumped into immune cells in the blood of the recipient, it would insert its DNA into these cells, stimulating them to release their own natural messenger RNA, thus spreading the message across the immune system to be alert to the presence of the coronavirus.

How effective was it in protecting against Covid?

A large clinical trial in 2020 showed that the Oxford/AstraZeneca vaccine offered strong protection against Covid-19, with an overall efficacy of 76 per cent. While this was lower than the Pfizer and Moderna vaccines, the Oxford/AstraZeneca vaccine had the advantage of being more robust, due to the resilience of adenoviruses. Because it didn’t require storage at ultra-cool temperatures, it was ideal for being transported around the world and played a key role in vaccinating people across low-income countries.

In 2021 alone, around 2.5 billion doses of the vaccine were administered globally, with studies showing that it saved an estimated 6.3 million lives. Dr Head says that it played a key role in reducing mortality rates from Covid-19 in India during the first half of 2021 when the delta variant was spreading rapidly through the country.

“Pfizer and Moderna’s vaccines had to be frozen, whereas one of the selling points of the AstraZeneca vaccine was firstly, it was cheaper, and also, it could be stored at fridge temperatures,” he says. “So for a couple of years, it was a vaccine for the world that could be used far more easily in low income settings, like for example in rural Africa.”

Why did people die?

The deaths and injuries are related to a very rare condition known as thrombosis with thrombocytopenia syndrome (TTS), causing the affected person to develop life-threatening blood clots around their body, ranging from the limb veins to major arteries, lungs, the abdomen, and the brain. People with TTS sometimes experienced initial symptoms ranging from breathing difficulties, chest pain, leg swelling, to persistent headaches, difficulty speaking and confusion, depending on where the clots were located.

This risk appears to have been higher in under-60s who received the vaccine, while young women seem to have been slightly more likely to develop TTS.

We still know relatively little about why certain, otherwise healthy individuals developed TTS as a consequence of receiving the vaccine, but one study suggested that in these rare cases, the adenovirus may have entered the bloodstream and accidentally bound to a small protein called platelet factor 4 (PF4). This could have triggered the immune system to mistakenly attack PF4, causing platelets to cluster together and form blood clots.

At the same time, Dr Head says it is important to remember that there was a far higher risk of developing blood clots from Covid-19 infection, compared to the vaccine. A 2021 study showed that for every 10 million people who received the AstraZeneca vaccine, approximately 66 people would develop blood clots in their veins and seven would develop clots in their brain. However, in comparison, if the same number of people were infected by Covid-19, 12,614 would develop clots in their blood vessels and 20 would experience clots in their brain.

But going forward, Prof Openshaw says it will be important to understand more about why vaccine-induced TTS occurred and how to prevent this risk in the design of future jabs.

“It’s so difficult when there are rare adverse effects to understand why they’ve happened, but it may be a great source of biological importance in future vaccine development to do so,” he says. “In the field of vaccines against respiratory syncytial virus (RSV), there was a trial by GSK that was using RSV vaccines in pregnant women, where they found there was an increase in the frequency of premature labour. Nobody understands why, but until we know, everyone feels very nervous about future vaccines of that sort. So understanding the mechanisms behind these rare and often inexplicable side effects is very, very important.”

I had the AstraZeneca vaccine. Should I be worried?

In short, no. Research showed that the risk of TTS was lower after the second dose of the vaccine than the first, and for people who experienced severe side effects, the development of clots happened relatively quickly.

“With any vaccine, the effects are noticed pretty quickly,” says Dr Head. “Anything that’s more neurological or related to blood clots, you probably would notice within one to three weeks. You wouldn’t get a sudden adverse event appearing years later. So people who’ve had the AstraZeneca vaccine dose in more recent times, if they’ve not had an adverse event now, they don’t need to be worried about anything occurring in the future.”

Why was the vaccine withdrawn?

This is believed to have been a purely commercial decision from AstraZeneca, rather than anything directly related to the cases of vaccine injury or the lawsuit.

Researchers point out that the demand for Covid vaccines is now much lower compared to three years ago, and the jab has been surpassed by those produced by Pfizer, Moderna and another company called Novavax.

“The AstraZeneca vaccine wasn’t quite as effective as these other vaccines, which is why they’re better bets going forward,” says Dr Head. “And we now know that the Pfizer and Moderna vaccines can be chilled rather than frozen for longer than was first thought, so the advantages of the AstraZeneca vaccine are less pronounced than they used to be.”