目前英国的疫苗接种政策是向COVID-19严重疾病高危人群提供未来的COVID-19强化剂量，但仍不确定哪些人群将受益最大。为了响应英国疫苗接种和免疫联合委员会的紧急请求，我们旨在在完成了COVID-19初级疫苗接种计划并接受了第一次强化疫苗的个人中确定COVID-19严重后果(即与COVID-19相关的住院或死亡)的风险因素。

在2021年12月20日至2022年2月28日期间，初级疫苗组的59510人(0.4%)和接受强化疫苗组的26100人(0.2%)出现了严重的COVID-19结果。在接受强化治疗后，发生严重COVID-19预后的风险降低(发生率变化:8.8次/ 1000人年至7.6次/ 1000人年)。老年人(≥80岁vs 18-49岁;aRR 3.60 [95% CI 3.45 - 3.75])，有共病者(≥5例共病vs无;9·51[9·07-9·97])

研究发现，老年人、多疾病患者和有特定基础健康状况的人在最初的疫苗增强剂后，COVID-19住院和死亡的风险仍在增加，因此应优先使用其他增强剂，包括新的优化疫苗和越来越多的COVID-19治疗方法。

Abstract

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.

文章连接：linkinghub.elsevier.com/retrieve/pii/S0140-6736(22)01656-7

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