Undervaccination tied to severe COVID-19 outcomes

In a meta-analysis of national cohort studies on COVID-19 vaccination across the UK (England, Northern Ireland, Scotland, and Wales), undervaccination was associated with a higher risk of severe COVID-19 outcomes (ie, COVID-19 hospitalization or death) relative to full vaccination.

The cohorts comprised 58.9M individuals in England, 1.9M in Northern Ireland, 5.0M in Scotland, and 2.4M in Wales. The corresponding rates of undervaccination in the respective cohorts were 45.8, 49.8, 34.2, and 32.8 percent. Undervaccination was defined as receiving fewer than the UK’s JCVI*-recommended standard SARS-CoV-2 vaccine schedule. [https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a]

Of the 40,393** severe COVID-19 outcomes reported across all cohorts, more than a third (n=14,156) were in undervaccinated individuals. [Lancet 2024;doi:10.1016/S0140-6736(23)02467-4]

Based on the extended adjustment analysis, it was estimated that in a counterfactual scenario whereby everyone in the UK was fully vaccinated on June 1, 2022, there would have been an associated reduction in severe COVID-19 outcomes by the end of follow-up – of 210 among individuals aged 5–15 years, 1,544 among those aged 16–74 years, and 5,426 in the subgroup of participants aged ≥75 years.

“Our modelling allowed us to estimate that full vaccination at the start of the study period would have been associated with a [total] reduction of 7,180 (~18 percent) severe COVID-19 outcomes from [all] severe events,” said the researchers. “Achieving target COVID-19 vaccination rates has the potential to reduce the incidence of severe COVID-19 outcomes in the future.”

In the meta-analysis, the adjusted hazard ratios (aHRs) for severe COVID-19 outcomes among individuals aged 16–74 years were 1.26 for a vaccine deficit of one dose, 1.88 for two doses, and 1.50 for three doses.

Among those aged ≥75-years, the aHRs for vaccine deficits of one, two, and three doses were 2.70, 3.13, and 3.61, respectively. In a separate report, Professor Martin Gulliford and Dr Claire Steves, both from King’s College London, UK, commented that it is noteworthy to point out that missing one vaccine (aHR, 2.70) has almost as large an association with severe COVID-19 outcomes as missing four vaccines (aHR, 3.08) in this patient subset. “This is likely to be accounted for by a known decline in vaccine-induced immunity over time.” [Lancet 2024;doi:10.1016/S0140-6736(23)02622-3]

The aHRs among those aged 5–15 years in Northern Ireland and Wales were not estimated owing to insufficient number of events.

In the common adjustment analysis, the odds of undervaccination were higher among those who were male, younger, from more deprived backgrounds, of non-White ethnicity, or had fewer comorbidities.

Mitigate severity of illness, not avoid infection

“These findings reinforce an important message – that the role of vaccination in COVID-19 is to mitigate the severity of the illness, [consequently] reducing the risk of complications and mortality, rather than avoiding all COVID-19 infections,” said Gulliford and Steves.

The results could serve as a springboard to formulate and tailor public health policies and interventions geared at improving vaccine coverage, as well as to better understand barriers to vaccination, especially among those who were deemed less likely to be fully vaccinated, the researchers noted.

“This knowledge is crucial to prevent exacerbation of existing inequalities and to provide insights for public health recommendations aimed at promoting vaccine uptake and improving health outcomes,” they added. “The study represents a notable step towards the goal of real-time pooled and federated health data analytics across the UK.”