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Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters

October 2022: Research published in The Lancet looks at who is at higher risk of serious illness following an Omicron infection, after a third or booster dose of COVID-19 vaccine.

Info-graphic showing highlights from this research paper. Read the article below to find out more.
This image was created by the Usher Institute, The University of Edinburgh to accompany a research study from the EAVE II associated Vaccine Breakthroughs Project, funded by the National Core Studies Immunity group and is a part of the Data and Connectivity National Core Study [MC_PC_20060] with support from the DaC-VaP-2 study [MC_PC_20058]. © 2022 Usher Institute, The University of Edinburgh. All rights reserved.

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

Agrawal, U; Bedston, S; McCowan, C; Oke, J; et. al

The Lancet

Published online on: 14 October 2022

Available online at: https://doi.org/10.1016/S0140-6736(22)01656-7 

Download the infographic (PDF)

This infographic was created by the Vaccine Breakthroughs Project's Communications & Engagement Officer, Gabriella Linning (Usher Institute, The University of Edinburgh)

Summary in Plain English

COVID-19 booster vaccine doses have been offered in the UK since September 2021. Booster vaccines can improve a person’s immune protection against disease, or help it last longer.

These were first offered to people known to be at high risk of becoming very unwell with COVID-19. From 29 November 2021, all adults were offered a first booster dose regardless of health conditions. This is because the Omicron variant of coronavirus SARS-CoV-2 caused a wave of infections in the UK. Either the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines were used as a booster.

Booster vaccines followed on from what was called a ‘primary schedule’ offered to all adults, and eventually young people. The UK primary schedule included two vaccine doses for most adults. The Oxford-AstraZeneca (ChAdOx1-nCoV-19) and Pfizer-BioNTech vaccines were most commonly offered. For people aged 12+ who have suppressed immune systems, a third half-dose of vaccine was also offered as part of the primary schedule.

Click here to read the current UK list of people at high risk of serious COVID-19 illness

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Why did we carry out this research?

Current UK policy is to offer further booster doses to people at high risk of serious COVID-19 illness. However, it is still not clear who will benefit most from being prioritised for booster vaccines.

Previously, we have shown using health data from Scotland that certain groups were still at increased risk of serious COVID-19 (i.e. COVID-19 related hospitalisation or death) after having their primary schedule of vaccines. This includes being older, having multiple health conditions, living in a care home or in a deprived area, being male, and being an ex-smoker.

Click here to read about our previous research in this area

The UK’s Joint Committee on Vaccination and Immunisation (JCVI) advises the UK Government on vaccine policy. They asked us to find out which groups are still at risk of becoming seriously ill with COVID-19 following an Omicron infection, after a first booster vaccine.

What data did we use?

We used health data from across the UK to carry out this study. These data are routinely collected from patients in England, Scotland, Wales and Northern Ireland in near-real time. Datasets are stored in each UK nation, in a Trusted Research Environment (TRE).

Click here to find out more about Trusted Research Environments (TREs) [Understanding Patient Data]

Studying very large numbers of people helps to provide precise evidence. This is important when finding people with specific or rare medical conditions who might be at risk. To do this securely, we looked at data separately in each UK TRE, and then studied the pooled results.

The datasets for Northern Ireland (1.9 million people), Scotland (5.4 million) and Wales (3.2 million) included relevant health information from 99-100% of the population. The dataset used for England contained information for 32% of the population, or over 19 million people.

From these datasets, we selected people aged 18 and over and who had their primary schedule and/or first booster dose between 8 December 2020 and 28 February 2022. This allowed us to compare people with and without a third vaccine dose. There were 16.2 million people across England, Scotland, Wales and Northern Ireland who fitted these criteria.

We looked for people who were admitted to hospital or died with COVID-19 between 20 December 2021 and 28 February 2022. This is when the Omicron variant was most common in the UK. We only included people who were seriously ill or died more than 14 days after a vaccine, as it takes time for a person to build up an immune response.

Click here to find out more about the data source we used in Northern Ireland

Click here to find out more about the data source we used in Scotland

Click here to find out more about the data source we used in Wales

What did we find?

We found that risk of COVID-19 hospital admission or death reduced for people who had a booster vaccine. Out of the 16.2 million people in the study, there were 13.8 million who had a booster dose of either Pfizer-BioNTech or Moderna.

Calculated for every 1 million people vaccinated, there were approximately:

  • 7,600 serious illnesses per year for people with a first booster;
  • 8,800 serious illnesses per year for people without a first booster.

COVID-19 risk before and after a booster vaccine dose

Although risk reduced overall, the risk factors for serious COVID-19 did not change much after a booster dose. This includes people who:

  • had their primary vaccines more than 10 weeks ago
  • live with multiple health conditions (‘multi-morbidity’)
  • are over 80 years old
  • are severely obese
  • are male.

We also found that having a SARS-CoV-2 infection between the primary schedule and booster had a protective effect, compared to people who had never been infected.

Health conditions and COVID-19 risk

The level of risk increased with the number of existing health conditions that people have. We then studied individual conditions known to put people at high risk of severe COVID-19. People with the following were shown to be at particularly high risk after a booster vaccine:

  • On treatments which suppress the immune system
  • History of a rare nervous system (neurological) condition
  • Chronic kidney disease (CKD) Stage 4 or 5.

Why is this research important?

This study is the first of its kind to identify people at high risk of COVID-19 after a first booster dose, using health data from a number of different national populations. In line with other studies, it confirms that having a booster dose reduced the overall risk of becoming seriously unwell with COVID-19 in the Omicron wave of the pandemic.

However, the same groups of people stay at highest risk after their primary and booster vaccines. These are older people, people with multiple health conditions, and certain health conditions including severe obesity, chronic kidney disease, immune system suppression, and rare nervous system conditions.

The results of this study will help to identify people who should be prioritised for vaccine boosters and treatments for COVID-19.  


This plain English summary was written by our Patient and Public Involvement Lead Lana Woolford, with the support and feedback of the EAVE II Public Advisory Group (PAG) and researchers.