Regulators in the UK and Europe have said it looks increasingly likely that several rare forms of blood clotting are linked to the AstraZeneca vaccine, noting that the evidence of the association is becoming firmer as more data becomes available.
However, both the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) have stressed that for the vast majority of people, the vaccine’s benefits outweigh its potential harms. By the end of March, when just over 20 million doses had been given in the UK, 79 people had suffered rare blood clots, and 19 had died. Up to the same point, COVID-19 vaccines are estimated to have saved around 6,000 lives in the UK.
Nevertheless, the acknowledgement that there probably is an association between the AstraZeneca vaccine and these clots will have an impact on who now receives it. This, though, will differ between the UK and Europe.
The EMA and MHRA have expanded their advice to patients and healthcare professionals, noting that the rare blood clots are associated with having low platelet levels, and so to look out for related symptoms such as continuous headaches or bruising distinct from the injection site. Importantly, neither agency could identify specific risk factors – such as sex or age – from their data, and therefore did not recommend any specific measures, such as age restrictions.
However, as cases have occurred across all age groups, and the risk of serious outcomes from COVID-19 decreases with age, the benefit of the vaccine relative to any risk it poses also falls as recipients get younger. This means that despite the regulatory agencies themselves not suggesting them, age restrictions are now being applied in many countries.
In the UK, the Joint Committee on Vaccines and Immunisation (JCVI) weighed up the risks and benefits of the AstraZeneca vaccine for various age groups. It made an independent recommendation that it would be preferable to offer an alternative vaccine to under-30s, since their risk of severe COVID-19 outcomes, such as intensive care admission, is low when the prevalence of the coronavirus is itself relatively low.
However, as the amount of circulating virus rises, the risk-benefit balance tips in favour of taking the vaccine, regardless of how old you are. If this decision had been made in January, while the second wave was still in full swing, it’s likely that this recommended age restriction wouldn’t have been suggested.
Indeed, presumably in light of this sliding scale of risk, the EMA noted that EU states should now make their own independent decisions about using the vaccine, based on their local COVID-19 status. Many, though, had already introduced quite significant precautionary restrictions on the vaccine while waiting for the EMA’s assessment, limiting its use strictly to older groups.
Given the EMA’s view that no age restrictions are needed, it might have been expected that these age restrictions would now be loosened to widen potential vaccine coverage. Certainly, the high prevalence of COVID-19 in many EU states, as well as the continent’s slow rollout of vaccines relative to the UK, would appear to make a less stringent judgement, akin to the JCVI’s, more compelling.
However, there are early indications that this isn’t going to happen. Italy has decided to give the vaccine only to over-60s and Belgium to over-55s. Additionally, Germany has resorted to vaccine mixing to avoid giving second doses of AstraZeneca vaccine to under-60s, despite there being no evidence that individuals who didn’t experience the rare blood clots after the first dose being at risk after the second.
What will the knock-on effects be in Britain?
The JCVI’s recommendation to offer other types of COVID-19 vaccine to people under 30 shouldn’t affect the UK vaccine programme. Alternative vaccines from Pfizer and Moderna have both been authorised for use, with future orders of these scheduled to arrive in time for the 20-29 age group’s vaccination window.
So assuming no supply issues occur, the UK’s vaccine programme should run as planned. However, some logistical changes to accommodate directing under-30s to vaccination centres that stock these alternative vaccines may be necessary.
A second consideration, though, is vaccine hesitancy. Over the past few months, the Office for National Statistics has been tracking the public’s vaccine sentiment, and has seen an increase from 78% vaccine positivity in December 2020 to 94% in late March 2021. This latter figure will reflect some of the early media coverage of the blood clot issue, but it is unclear at present how more recent communications will affect public confidence. Hopefully, the clear and transparent communication from the MHRA and JCVI about risk, and these decisions being taken out of the hands of politicians, will help maintain public trust. Time will tell.
The foreknowledge that the vaccines would be introduced in the middle of a pandemic, and the need to ensure public confidence, led both the EMA and the MHRA to create safety monitoring and communication plans for COVID-19 vaccines in mid-2020. In the UK, it was an existing monitoring system – the Yellow Card scheme, where people report suspected side-effects they’ve encountered – that detected this safety signal. This should provide confidence that rare side-effects can be detected for any of the vaccines licensed.
While many may have been unaware of these crucial systems until now, continued trust in these processes – by both the public and national governments – will be essential for the success of the vaccination campaigns.
Anthony R Cox is an honorary pharmacovigilance pharmacist at the Yellow Card Centre West Midlands.