As the rollout of first dose COVID-19 vaccines accelerated in the UK and Europe, safety concerns emerged after reports that a small number of people experienced adverse events in their blood. Urgent research was needed to identify, quantify and, if possible, mitigate the problem. This paper gives the findings of a swift population-level study in Scotland which showed that while there were risks from the first dose of the Oxford-AstraZeneca vaccine, adverse events were very rare; no such risks were identified with the Pfizer-BioNTech vaccine.


By 21 April 2021, 22m first doses and 6.8m second doses of the Oxford-AstraZeneca vaccine had been delivered in the UK. However the MHRA (Medicines and Healthcare products Regulatory Agency) had reports of 209 people in the UK suffering adverse blood events after receiving the vaccine. The European Medical Agency (EMA) had 169 reports of central venous thromboembolic (a rare brain bloodclot) events by 4 April. Some countries halted or limited use of the vaccine. There were also concerns that safety fears would drive vaccine hesitancy among the public.


One of the UK’s Chief Scientific advisers approached the EAVE II team at the University of Edinburgh (and supported by HDR UK BREATHE Hub for respiratory health) to investigate these concerns using the large-scale patient data available in Scotland.

The team, which included Professor Aziz Sheikh and Professor Colin Simpson took just 5-6 weeks to carry out peer-reviewed research into patient-reported problems from 2.53m (57.5%) of the Scottish population. This covered the 1.71m who had received the Oxford-AstraZeneca and 0.82m who had received the Pfizer-BioNTech vaccine.

Their work covered idiopathic thrombocytopenic purpura (ITP), venous thromboembolic, arterial thromboembolic and haemorrhagic events. The resulting paper was published in Nature Medicine (July, 2021).

Lessons learnt

No link was found between the Pfizer-BioNTech vaccine and any of the adverse events under study. The first dose Oxford-AstraZeneca vaccine was linked to a small increase in ITP (113 cases per 10m doses). There was a suggestion of increased risk of thromboembolic and haemorrhage events following Oxford-AstraZeneca vaccine. And there was no rise in venous thromboembolic events. The risk level was similar to other common vaccines and, according to Prof. Sheikh, the likelihood of these events is “orders of magnitude higher” among those who contract COVID-19.

Prof. Sheikh said:

“One of enduring lessons is that COVID-19 vaccines have probably come under more scrutiny than any other vaccine in history. We’re going to understand their safety profile incredibly well. Hopefully, once we’re through this, we can turn the same degree of scrutiny to other vaccines.”

Impact and outcomes

The research team reported its initial findings to policymakers. This helped them to develop take precautions to protect those who might be at risk. It also reassured the public – providing them with evidence-based information.

The team has been following up with studies of other vaccines and will carry out work on second doses. Research may also take place into booster jabs.

Patient and Public Involvement and Engagement

EAVE II has a Public Advisory Group, which shapes its work and reporting – including the creation of infographics and lay summaries.

HDR UK Impact Committee

The HDR UK Impact Committee serves to raise the profile of both ours and our contributors’ outputs.  The Impact Committee are keen to celebrate significant impacts which clearly demonstrate the value of of our mission to unite the UK’s health data to enable discoveries that improve people’s lives.


Prof. Sheikh OBE: aziz.sheikh@ed.ac.uk