In a recent article published in The Lancet, researchers examined the association between under-vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe coronavirus disease 2019 (COVID-19) outcomes across the United Kingdom (UK).
Study: Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales. Image Credit: solarseven/Shutterstock.com
Background
Previous studies have examined vaccine uptake in the UK; however, population-level studies examining the risk of severe COVID-19 outcomes in under-vaccinated people are lacking.
The UK COVID-19 vaccination programme started on December 8, 2020. The Joint Committee on Vaccination and Immunisation (JCVI) recommended one COVID-19 vaccine dose for children aged five to 11 years, two for 12–15-year-olds, and three and four for people aged 16–74 and 75+.
Over 90% of the UK population above 12 years received the first dose of a COVID-19 vaccine within a few months; however, its uptake declined as more doses were offered, especially among Black ethnicities, those older than 50 years, and those inhabiting more deprived or urban areas.
Clinical trials and observational epidemiological studies have shown the association of COVID-19 vaccine doses with COVID-19 outcomes, such as hospitalizations and deaths.
About the study
Researchers conducted separate cohort studies in England, Scotland, Northern Ireland, and Wales using anonymized, harmonized electronic health record (EHR) data from national trusted research environments (TREs).
All four study cohorts included individuals at least five years of age, further stratified into groups: 5–11, 12–15, 16–74, and ≥75 years.
The outcomes of interest were the adjusted odds ratios (aORs) for under-vaccination against SARS-CoV-2 as of June 1, 2022, and severe COVID-19 outcomes between June 1 and September 30, 2022.
Undervaccination, i.e., non-receipt of the standard age-stratified JCVI recommended vaccine schedule, was assessed in each nation for several clinical and demographic groups and cumulatively.
The statistical analysis included these covariates: age group, gender, ethnicity, urban or rural residence, deprivation index, and QCOVID risk groups, derived primarily from general practitioner data, and its availability for some UK nations was limited.
For instance, ethnicity and public practitioner data were not available for Northern Ireland.
The team analyzed time to severe COVID-19 outcomes in different age groups separately for each nation using Cox proportional hazard models, where vaccine deficit was a time-dependent exposure.
Likewise, they fitted in logistic regressions across age groups to analyze under-vaccination as the dependent variable.
Additional tests helped the researchers assess collinearity and model performance, etc., where they used more covariates, such as COVID-19 test results, number of tests taken, health board, shielding status, size of household, and hospitalizations, including COVID-19-unrelated hospitalizations.
Finally, the researchers conducted a UK-wide meta-analysis of nation-specific analyses. In this study, they compared the estimates of the decrease in severe COVID-19 outcomes associated with under vaccination with a counterfactual scenario, where the UK population was fully vaccinated for COVID-19 by June 1, 2022.
Results
As of June 1, 2022, the number of people under-vaccinated in England, Northern Ireland, Scotland, and Wales was 26,985,570, 938,420, 1,709,786, and 773,850.
These numbers corresponded to 45·8%, 49·8%, 34·2%, and 44·4% of the initial cohort size of each nation.
The effect size estimates for the number of risk groups varied across countries in the analysis where undervaccination was the outcome.
For instance, aORs for under vaccination were higher in individuals aged 80–84 years and 85+ in Scotland compared with other nations.
It reflected different data availability for QCOVID risk groups and residual confounding from the number of risk groups.
Further, the study results suggested that younger individuals, those from more deprived regions, and of non-White ethnicity, or those with fewer comorbidities were more likely to be under-vaccinated for COVID-19.
Accordingly, of 40,393 severe COVID-19 outcomes across cohorts, 14,156 occurred in unvaccinated participants.
Reductions in severe COVID-19 outcomes over four months of follow-up varied for age groups; these were 210, 1,544, and 5,426 for 5–15, 16–74, and 75+ years age groups, respectively.
In the meta-analysis for the ≥ 75-year-olds, aHRs for severe COVID-19 outcomes were 2.70, 3.13, 3.61, and 3.08 for one, two, three, and four dose(s) fewer than recommended.
Moreover, males in this age group showed higher aHR of severe COVID-19 outcomes than females.
Conclusions
The present study furnished precise estimates for the association between full vs. under vaccination and higher risk of severe COVID-19 outcomes for the four UK countries.
Results indicated that under-vaccination rates against COVID-19 in these UK countries ranged from 32·8%-49·8% among individuals aged five years or more.
Further analysis showed that had been the vaccine uptake higher, it would have resulted in a considerable reduction in severe COVID-19 outcomes, especially among at-risk subpopulations in the UK. This data could inform policy, public health, and research.
More importantly, the study highlights the significance of analyses on harmonized health datasets across the UK as it could be beneficial in understanding population health outcomes to help design better future health interventions.