Severe COVID-19 outcomes after full vaccination of primary schedule and initial
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.
Introduction
Three vaccines have mainly been used in the UK—namely, BNT162b2 (tozinameran; Pfizer–BioNTech), ChAdOx1 nCoV-19 (Oxford–AstraZeneca), and mRNA-1273 (elasomeran; Moderna).
In the UK, the primary vaccination schedule is two doses for the majority of the population or three doses for people who are immunosuppressed. Booster doses have been offered in the UK since September, 2021, initially for groups at high risk of serious illness from COVID-19. However, the rapid emergence of the more transmissible omicron (B.1.1.529) variant of concern (relative to delta [B.1.617.2])—which was first seen in the UK in late November, 2021, and became the dominant variant by mid-December—led to considerable concern in public, professional, and government circles, resulting in a policy initiative to fast-track the roll-out of the booster vaccine, including to younger people (all those aged 40 years and older), in an attempt to prevent yet another UK-wide lockdown over Christmas, 2021. From Nov 29, 2021, booster doses were then extended to those aged 18 years and over, with a recommended gap of 3 months after primary vaccination.
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