Rollout of the AstraZeneca vaccine continues to be impaired by variation in guidance on its safety, and on who should receive it.
The latest twist is the decision by the National Immunisation Advisory Committee (Niac), which advises the Government on vaccination, to revise its advice yet again – and to recommend it be restricted to “those aged 60 years and older including those with medical conditions with very high or high risk of severe Covid-19 disease”.
Initially supply difficulties hampered its distribution but, of late, increased reports of blood-clotting complications post-vaccination have undermined its deployment.
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In spite of these rare cases, it remains a highly effective vaccine in preventing severe Covid-19 illness and death, though a causal link is suggested between those side effects and a very small number of fatalities.
There is, however, much confusion because of differences in guidance depending on where you live – not forgetting instances where some countries (including Ireland) previously limited its use to younger people, and yet are now giving it to older people only.
How have we got to this point?
The European Medicines Agency (EMA) last week concluded unusual blood clots in the brain with low platelet numbers (cells which normally help your body form clots to stop bleeding) are a rare side effect. But benefits from protection AstraZeneca provides greatly outweigh the risks – especially in older people.
Its decision coincided with the UK vaccination advisory body abruptly changing its guidance by recommending healthy adults under 30 should be offered an alternative vaccine to the jab if one is available and they are not at high risk of Covid.
With Ireland at the initial stages of its vaccination programme, the associated uncertainty is unhelpful, especially when widespread vaccination is the best way to getting closer to normality in the quickest possible time.
Niac, none the less, decided to re-examine the evidence, though it initially did not change its advice issued in mid March, which was aligned to that of the EMA.
While this is an extremely rare condition, it says consideration must be given to the fact it has a very high risk of death or severe outcome. So on balance – taking into account EMA reports – and because alternative Covid-19 vaccines are available, it revised its guidance.
What are the latest indications on the clotting problem linked to the AZ vaccine?
Of 34 million people who had received the vaccine in the UK and the European Economic Area, the EMA said it had received reports of 169 cases of cerebral venous sinus thrombosis (CVST) and 53 cases of splanchnic vein thrombosis – both rare kinds of blood clots.
Most were in women under 60, but the evidence does not suggest age or gender is a risk factor for the side effects, the EMA said. All these cases arose some 14 days after receiving the first dose. The first Irish case of CVST was confirmed last week.
The cases, none the less, prompted the EMA to advise product information be updated to describe the conditions as a rare side effect, with a warning to be aware of early symptoms including severe persistent headache, blurred vision, and skin bruising beyond the site of injection.
Why were younger women previously considered most at risk?
In spite of early indications, the rare clots are as common in men as women. There has been intense evaluation of a possible mechanism for the unusual combination of effects giving rise to clots and fatalities – which are different to clots found, for instance, in the leg.
Some experts suggested possible explanations could be oral contraceptives, pregnancy or hormonal replacement therapy which increase risk of clots in normal circumstances.
The EMA and the UK regulator have concluded the reason for more cases in women could largely be due to more women working in healthcare; most of whom have been prioritised for vaccination.
What are people over 60 to make of the latest guidance?
The risk-benefit profile of the AstraZeneca vaccine is strongly in favour of its use, notably when factoring in high clot risk associated with severe Covid-19 among older people.
That said, there is an inevitable perception issue which requires careful and balanced public health messaging, especially in relation to older people.
The latest difficulty has prompted speculation in the US that it won’t need the AZ vaccine because of increased availability of other vaccines – it has yet to approve it for use. All this is an invidious position to be in for what was once called a “game changer” in the global fight against the virus.
The insidious traits of Covid-19 and emergence of new variants, however, will not allow for choice among the vast majority of recipients – though advice will continue to be evaluated and adjusted, if necessary, based on reported side effects.
How reliant is Ireland on the AZ vaccine?
It is one of four approved for use here. The Niac decision clearly means the vaccination programme will need significant revision.
In the first quarter of 2021, 340,800 doses out of 1.19 million delivered were AZ jabs (29 per cent). For the second quarter some 813,000 doses are due to be delivered out of 3.9 million expected by the end of June (21 per cent) – around 420,000 people aged between 70 and 80 in the State are due to be vaccinated.
If AstraZeneca cannot be given to younger groups, it effectively means “there’s less vaccine available and more people to vaccinate”, according to Dr Denis McAuley, chair of the Irish Medical Organisation’s GP committee.
“It confuses an awful lot of things, really,” he said. The issue of second doses for those who have received a vaccine will also need to be addressed. “Some 233,000 people have been given their first dose of AstraZeneca so far, and the decisions would be needed for those under 60 in this number. It must be decided whether they are given their second dose, whether a second dose from another manufacturer is given, or whether they are vaccinated with two entirely new shots.”
In the UK the AZ jab has been the workhorse in its successful vaccination programme. Equally, many countries have been banking on it as it is cheap and easier to administer as it can be stored at normal refrigerator temperatures for at least six months.
Is Irish advice now at considerable variance to the EMA position?
Ireland’s regulator, the Health Products Regulatory Authority, together with other EU medicine regulators, was part of the EMA review through membership of its safety committee. That process was very thorough.
Separately, however, Niac constantly evaluates regulatory issues including EMA and WHO guidance and the latest scientific evidence.
The hard lessons of Covid-19 indicate a frequently changing picture. As vaccination rollout continues, risk-benefit needs to be weighed up in light of emerging evidence. That is a complex process, with differing priorities and approaches in different jurisdictions.
After the revised EMA guidance, Prof Adam Finn of the University of Bristol explained the process: “UK and European regulators are alert to any events occurring after vaccination, whether or not coincidentally, and they use careful scientific reasoning to tease out whether there may be any causal link.”
They need to tread the right path between the perils of raising false alarms which may result in the loss of many human lives by denying people protection from Covid-19 through vaccination on one hand, he explained, and failing to notify the public and the medical profession about potential problems that may exist so they can be promptly diagnosed and treated.
The overall risk-benefit assessment has come down in favour of its continued use in older people, given risk of catching Covid-19 is hundreds of times more likely than suffering a blood clot after being vaccinated with the AZ jab.
It also takes into account younger people are at much lower risk of getting Covid-19. The bottom line remains: if you get severe Covid-19, your chances of getting a clot are far higher.