Deciding which groups should be prioritised was critical to the UK’s plans for a programme of second COVID-19 boosters. The UK Joint Committee on Vaccination and Immunisation (JCVI) made an urgent appeal for data on which social groups were most at continued risk from severe COVID-19 outcomes. Research part-funded by HDR UK provided a detailed population-level analysis covering all four nations which was invaluable in guiding targeting decisions.


After an initial vaccination and booster campaign, UK policymakers planned to offer second boosters and needed to know who was most at risk of serious COVID-19 outcomes (hospitalisation or death) so they could be prioritised.

This would require a rapid meta-analysis of primary, secondary and other patient healthcare data from England, Scotland, Wales and Northern Ireland. As each of the four nations has its own approach to data gathering, one of the major challenges was drawing it together into a single, accurate analysis.


Researchers responded by conducting an analysis based on a cohort drawn from 30 million people. They then focused on those who had received a primary vaccination (two injections) using the Pfizer–BioNTech and Oxford–AstraZeneca vaccines and a booster using either the Moderna or Pfizer–BioNTech vaccine.

It was the first national study of the risk of severe COVID-19 events in the UK population who had received a booster dose.

The results were shared with the JCVI and other stakeholders and were published in a paper entitled Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales (The Lancet, October 2022).

During the research there was extensive patient and public involvement and engagement (PPIE). This materially affected the research with PPIE advisors asking for learning disabilities to be included as a potential risk factor.


The analysis provided policymakers with timely insights for the booster campaign.

They showed that older people, those with multimorbidity, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised.

The increased clinical risk for older people is likely to reflect underlying frailty, comorbidity, and immune senescence.

Other key risk factors included chronic kidney disease, neurological disorders, heart failure, and chronic obstructive pulmonary disease. Most importantly there was an increased risk associated with high multimorbidity.

Lead author, Dr Utkarsh Agrawal, a Research Fellow in Health Data Science at the University of St Andrews, said: “At each step our results were being presented to the JCVI groups. The decision on who to prioritise for the second booster was based on multiple works, but primarily on the research presented in this paper.”

Other findings included an increased risk of severe COVID-19 outcomes beginning 10 weeks after completing the primary vaccination.

The researchers identified that those who had been infected with COVID-19 enjoyed some additional level of protection, but suggested that this might not reduce their vulnerability to new variants.

The team is now looking at the performance of second boosters and the impact of monoclonal antivirals.

What the Impact Committee said:

The committee described this research as “rigorous” with a strong policy-relevant impact and a commitment to open science. The paper was praised for its contribution to public health and for addressing COVID-19 outcomes from all four UK nations.


Email utkarsh.agrawal@phc.ox.ac.uk.