Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales
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Background Under-vaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) may be associated with increased risk of severe COVID-19 outcomes (i.e., COVID-19 hospitalisation or death) compared to full-vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with under-vaccination, and to investigate the risk of severe COVID-19 outcomes in people who were under-vaccinated in each UK nation, and across the UK. Methods We used anonymised, harmonised electronic health record (EHR) data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland and Wales. We estimated adjusted odds ratios (aORs) for under-vaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes over the period June 1 to September 30, 2022, with under-vaccination 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 where everyone in the UK was fully-vaccinated on June 1, 2022. Findings The percentages of people under-vaccinated (number of individuals in cohort) on June 1, 2022 were 45.7% (58.9 million), 49.8% (1.8 million), 34.2% (5.0 million) and 32.8% (3.5 million) in England, Northern Ireland, Scotland and Wales, respectively. People who were younger, from more deprived backgrounds, of non-white ethnicity or had lower number of comorbidities were less likely to be fully-vaccinated There was a total of 40,411 severe COVID-19 outcomes in the cohorts, with 14,165 in the under-vaccinated. We estimated the reduction in severe COVID-19 outcomes by the end of follow-up associated with full vaccination on June 1, 2022 (95% confidence intervals (CIs)) as 210 (94, 326), 1,544 (1,399, 1,689) and 5,426 (5,340, 5,512) in the 5-15, 16-74 and ≥75 year age groups respectively in the UK. Adjusted hazard ratios for severe COVID-19 outcomes in the meta-analysis for the ≥75 year age group (95% CIs) were 2.70 (2.61, 2.78), 3.13 (2.93, 3.34), 3.61 (3.13, 4.17) and 3.08 (2.89, 3.28) for 1, 2, 3 and 4 doses fewer than recommended. Interpretation Rates of under-vaccination against COVID-19 ranged from 32.8% to 49.8% across the four UK nations. in summer 2022. Under-vaccination was associated with an elevated risk of severe COVID-19 outcomes.
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1474-547X