Undervaccination and Severe COVID-19 Outcomes: Meta-Analysis of National Cohort Studies in England, Northern Ireland, Scotland, and Wales

Background Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK. Methods We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022. Findings The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (458%) of 58 967 360 in England, 938 420 (498%) of 1 885 670 in Northern Ireland, 1 709 786 (342%) of 4 992 498 in Scotland, and 773 850 (328%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 270 (261-278) for one dose fewer than recommended, 313 (293-334) for two fewer, 361 (313-417) for three fewer, and 308 (289-329) for four fewer. Interpretation Rates of undervaccination against COVID-19 ranged from 328% to 498% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.