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

Utkarsh Agrawal, Stuart Bedston, Colin McCowan, Jason Oke, Lynsey Patterson, Chris Robertson, Ashley Akbari, Amaya Azcoaga-Lorenzo, Declan T Bradley, Adeniyi Francis Fagbamigbe, Zoe Grange, Elliott C R Hall, Mark Joy, Srinivasa Vittal Katikireddi, Steven Kerr, Lewis Ritchie, Siobhán Murphy, Rhiannon K Owen, Igor Rudan, Syed Ahmar ShahColin R Simpson, Fatemeh Torabi, Ruby S M Tsang, Simon de Lusignan, Ronan A Lyons, Dermot O'Reilly, Aziz Sheikh* (Corresponding Author)

*Corresponding author for this work

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Abstract

Summary Background Current UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine. Methods We constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses. Findings Between Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs female; 1·23 [1·20–1·26]), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53–6·09])—and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90–4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]). Interpretation Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics. Funding National Core Studies–Immunity, UK Research and Innovation (Medical Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.
Original languageEnglish
Pages (from-to)1305-1320
Number of pages16
JournalThe Lancet
Volume400
Issue number10360
Early online date14 Oct 2022
DOIs
Publication statusPublished - 15 Oct 2022

Bibliographical note

This work was funded by the National Core Studies–Immunity group.
This research is part of the Data and Connectivity National Core Study,
led by Health Data Research UK in partnership with the Office for
National Statistics and funded by UK Research and Innovation (grant ref
MC_PC_20060), with support from the DaC-VaP-2 study also funded by
UK Research and Innovation (grant ref MC_PC_20058). The study
entitled “Use of national linked health care, serological data, and viral
genomic data to identify and characterise post-third and -booster dose
vaccine breakthroughs at a population level” is a partnership between
the University of Edinburgh, Swansea University, Oxford University,
Queen’s University of Belfast, University of St Andrews, and The Office
for National Statistics. The authors would like to acknowledge all other
project collaborators not involved in these analyses but who are
contributing to wider discussions and preceding outputs. EAVE II is
funded by the Medical Research Council (MR/R008345/1) with the
support of BREATHE–The Health Data Research Hub for Respiratory
Health (MC_PC_19004), which is funded through the UK Research and
Innovation Industrial Strategy Challenge Fund and is delivered through
Health Data Research UK. Additional support has been provided
through Public Health Scotland and Scottish Government Director-General Health and Social Care.

Data Availability Statement

Data sharing
A data dictionary covering the data sources used in this study can be found at https://github.com/EAVE-II/EAVE-II-data-dictionary. All codes used in this study are publicly available at https://github.com/EAVE-II/Covid-breakthrough-post-first-booster/. The data used in this study are sensitive and will not be made publicly available.

Supplementary material
See Online for appendix.

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