In defence of the AstraZeneca vaccine – and what comes next

The pharmaceutical giant has struggled to maintain trust in its product. But as faith in the vaccine continues to flag after the blood clot saga, the world cannot afford to forget what is on offer, writes Samuel Lovett

Governments and citizens are collectively losing trust in the AstraZeneca vaccine (AFP via Getty Images)

Initially lauded as a tool with which to ease humanity’s passage out of the Covid-19 pandemic, the AstraZeneca-Oxford vaccine has since fallen from favour in many parts of the world, where it is now viewed with suspicion and concern.

It is currently caught in its greatest crisis of confidence to date, following the conclusion it appears to be linked to rare blood clots detected in some recipients of the jab. Investigations into these events are ongoing, but the data show that the risk of death from such a side effect is negligible: roughly one in a million.

Irrespectively, the vaccine’s image has taken yet another pummelling, having already faced down politically-charged attacks and disparaging discourses from the continent – despite evidence pointing to its efficaciousness.

Yet the veneer has been fading ever since the jab’s efficacy and safety was first confirmed during the dark months of the second wave. Controversy around the vaccine has been bubbling away for months, fuelled by one flashpoint after another – some of which AstraZeneca carries and accepts responsibility for.

These include the half-dose testing mishap; confusion around the jab’s overall efficacy and the manner in which trial data was pooled from different studies; wrongful allegations of being “quasi-ineffective” among the elderly; delayed and reduced supplies to the EU; 29 million “hidden” doses that were “discovered” at an Italian factory; and a rare public admonishment issued via US health officials after AstraZeneca released “outdated” results from its American trial. The list goes on.

Many of these have been “self-inflicted injuries,” says Martin McKee, a professor of European public health at the London School of Hygiene and Tropical Medicine. The British-Swedish pharmaceutical has struggled to grasp the fundamentals of good PR and maintain trust in its product – yet at times it feels the scale of what AstraZeneca has achieved and offered has been forgotten by many.

This time last year, there was no end in sight to the end of the pandemic. Dr Anthony Fauci, the White House’s chief Covid-19 adviser, warned the world would not have a vaccine until several months into 2021. Others feared a longer timeframe. And of those experts who were optimistic, there was consensus that 50 per cent efficacy would represent a remarkable feat.

However, the team at Oxford University and AstraZeneca – along with their counterparts at Pfizer/ BioNTech, Moderna and elsewhere – succeeded in proving the doubters wrong and simultaneously exceeding all expectations. 

To date, close to 200 million doses have been delivered globally by AstraZeneca, while Pfizer has rolled out even more. Both have a long way to go in reaching their total agreed supply target for 2021 – 3.3 and 1.6 billion respectively – but these figures nonetheless point to the progress of science and a reality that few imagined possible 12 months ago.

The AZ vaccine is also unique in that it is servicing a truly global market. As of 30 March, some 32 million doses had been distributed to 70 countries – nearly two-thirds of which were low- or middle-income in status.

To put that number in context, this is just six per cent of the 564 million doses that had been administered worldwide. This inequality, the byproduct of a much larger system, is likely to persist for years and will only hamper the efforts of the global south – and by extension, the developed world – to contain the pandemic.

AstraZeneca is one cog among many in a machine tailored to the needs of the west, but it cannot be accused of wholly neglecting the poor. It has committed 170 million doses to the world’s poorest nations, and sub-contracting deals are in place with the Serum Institute of India to increase this figure to 1.1 billion.

The AZ vaccine is crucial to global efforts to overcome Covid-19 (AFP via Getty Images)

This is all being done “at-cost”, meaning AstraZeneca won’t make a profit off the 3.3 billion doses it intends to deliver this year. In contrast, Moderna expects to make $18bn (£13bn) in revenue from its vaccine and Pfizer/BioNTech $15bn (£11bn). Both manufacturers are almost exclusively accommodating western populations, and stand to make billions from doing so.

With almost three million people now dead from coronavirus, hospitals still overwhelmed in many nations and cases once again surging in some of the most vulnerable corners of the globe, the value of AstraZeneca’s vaccine – which is cheap, easy to store and highly effective – cannot be underestimated. Especially so in those countries where healthcare is limited and vaccination offers the only real protection against Covid.

Yet insiders at AstraZeneca are “frustrated” that sight of the “bigger picture” has been lost, while even the Oxford team – ever reluctant to wander beyond the world of science – has been taken aback at the politicisation of their vaccine. There is a sense in both camps that the scandalised narratives that have emerged in recent months are costing lives.

Unfortunately, the AZ vaccine now finds itself approaching somewhat of a crossroads. The blood clot link has changed the lay of the land and presented a new obstacle for politicians, health experts and public officials to overcome in encouraging their populations to accept this vital jab.

The condition causing alarm is called cerebral venous sinus thromboses (CVST) , in which blood clots form in the veins that run from the brain, sometimes culminating in death. In the cases of concern, which appear to be more prevalent in people under 60, this has been combined with thrombocytopenia, where a patient presents abnormally low levels of platelets.

The UK’s medicines regulator says it has identified 79 cases of CVST and thrombocytopenia, out of more than 20 million administered doses of the vaccine. Nineteen recipients of the jab have died. On the continent, higher rates of incidence have been recorded, possibly because mainland Europe has given the AstraZeneca vaccine to more people under 60 than Britain.

Last week, a review by the European Medicines Agency’s safety committee concluded that clotting "should be listed as very rare side effects” of the vaccine – though the body insisted the jab remains safe to use and should continue to be administered in adults.

Determining causation remains another matter. Researchers in Germany have speculated that the vaccine could be provoking an overexcited immune response in some people, causing them to generate antibodies that target blood platelets. Others have spotted similarities to a thromboembolic reaction suffered by patients treated with heparin, a blood-thinning medicine.

It’s unknown whether the affected individuals share underlying conditions which predispose them to such reactions, but national regulators have understandably taken swift action, with the vast majority limiting the vaccine’s use to older people as a precautionary measure. In the UK, the Joint Committee on Vaccination and Immunisation (JCVI) has recommended that people under 30 be offered an alternative jab.

More clots and deaths will no doubt be reported in the coming weeks, and a firmer link may be established, but this cannot be allowed to further darken the narrative surrounding the AZ vaccine. Even in spite of these rare adverse reactions, the benefits of protecting against Covid-19 – which is surging once again in Europe, Latin America and India – still far outweigh the risks.

The data demonstrates this. Should a million 60-year-olds catch coronavirus, around 20,000 would die. This drops to 1,000 for a million 40-year-olds, or a few hundred for people in their 30s. Of a million people to be vaccinated with the vaccine, one individual will die. These may well vary with age and gender, but the risk remains infinitesimal nonetheless.

"If you are currently being offered a dose of Oxford-AstraZeneca vaccine, your chances of remaining alive and well will go up if you take the vaccine and will go down if you don’t,” says Professor Adam Finn, a member of the JCVI.

Realistically, no medicine is perfect or 100 per cent safe. Even paracetamol and ibuprofen carry a very rare risk of death, yet these drugs continue to be consumed by millions of people on a daily basis due to the benefits they confer. The public has reconciled itself with these facts, and will likely have to do the same with the AZ vaccine.

In the UK, there are already signs of this happening. A new YouGov survey showed that 75 per cent of British respondents says that they still trust the AZ jab – a stark contrast to similar research conducted across Europe where, even before this week’s announcements, faith in the vaccine was worryingly low.

The real fear is that lingering distrust in the vaccine spreads beyond the west to countries within the global south

Variation in guidance for the vaccine is unlikely to inspire any newfound confidence on the continent. In some countries, such as Norway, the jab remains suspended for use, while in others, like France and Germany, its administration is now limited to people aged over 55 and 60 respectively.

This patchwork of regulation is certainly “not unexpected” and has been done “out of an abundance of caution to maintain confidence,” says Dr Claas Kirchhelle, a medicines historian at University College Dublin. 

“It's not uncommon for regulators in different countries to come to different risk assessments,” he adds. “Every risk evaluation follows an inherent system of what the public, politicians and regulators value most within that culture and country. Germany, for example, has historically been conservative with regards to vaccines and safety profiles.”

But faced with such disunity, winning back the people of Europe will be tricky. Matters are not helped by the political and scientific sandstorms that have already engulfed AstraZeneca. “Once you've lost trust it's very difficult to get it back,” says Prof McKee.

Relations with the EU are on thin ice following the company’s failure to meet its supply targets for the bloc. Having initially promised 90 million doses by the end of March, AstraZeneca now believes it will be able to offer 50 million come the end of this month. The manufacturer is disappointed by this shortfall, and politicians have warned that the delays will cost lives.

Countries like Brazil are seeing a surge in Covid-19 cases, reinforcing the importance of the AZ vaccine (AFP via Getty Images)

Tensions have manifested themselves in ugly ways, the most recent example being the raid carried out on an AstraZeneca plant in Italy that was alleged to be “hiding” 29 million doses, said to be intended for the UK. One company insider says the EU-led inspection, which found that the supplies were destined for Europe and the developing world, reached “conspiracy-like levels” and provided an “illustration of what we’re dealing with”.

Across the pond, US attitudes towards AstraZeneca can be described as lukewarm at best. Last month, the National Institutes of Health (NIH) accused the company of using “outdated information” in its large-scale US study, which may have provided "an incomplete view” of the vaccine’s effectiveness.

The company had used data up to 17 February. This showed there had been 141 Covid infections among trialists and that the vaccine was 79 per cent efficacious. More data was added two days later, and efficacy was revised downward to 76 per cent. Scientists feel that such a dispute never needed to go public and was nothing more than a “storm-in-a-teacup” – but one that will have further damaged confidence in the vaccine.

Although US health officials appear to have been satisfied, it remains unclear if and when approval for the jab will be granted – especially with the question marks that now hang over the blood clots.

The real fear is that lingering distrust in the vaccine spreads beyond the west to countries within the global south. According to data from the World Health Organisation, roughly 50 per cent of all global vaccine deals struck by AstraZeneca are targeted at low-and middle-income countries. 

Global Justice Now, which campaigns on issues of healthcare and trade in the developing world, says these nations were “desperately reliant” on AstraZeneca doses and that any misconceptions or “concerns over the vaccine could reduce take-up of even the very limited supplies countries have received”.

This is where politicians, governments and health officials come into play. Clearly communicating the risk-to-benefit ratio to patients will be vital to maintaining vital uptake of the vaccine, especially in those countries that do not have the privilege of discarding the AZ jab and turning to another.

Despite all this, there are undoubtedly more trials and tribulations that lie ahead. While its main competitors have been gifted a free-pass – despite their fair share of production dips, contamination setbacks and safety-related incidents – for a myriad of reasons, the AZ jab has found itself blackmarked. Much of this scrutiny has been warranted; some has arisen from EU-UK tensions; and other elements of the controversy are rooted in AstraZeneca’s own shortcomings.

These details needn’t be forgotten, but nor should they overshadow the “bigger picture” here – or derail efforts to vaccinate as many people as possible within the parameters of what is feasible.

Perhaps with hindsight, once a greater array of shots have been developed and taken centre stage, the AstraZeneca vaccine will be recognised for what it is: a critical, life-saving tool which has carved out one of the first pathways to life after Covid-19.