Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales.
Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales.
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DOI：
10.1016/s0140-6736(22)01656-7
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发表时间：
2022-10-15
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英国目前的疫苗接种政策是为高风险的COVID-19严重疾病患者提供未来的COVID-19加强剂，但仍不确定哪些人群可能受益最大。为响应英国疫苗接种和免疫联合委员会的紧急要求，我们旨在确定已完成COVID-19初次疫苗接种计划并已接种第一次加强疫苗的个人出现严重COVID-19结果（即COVID-19相关住院或死亡）的风险因素。我们通过初级保健，RT-PCR检测，疫苗接种，住院和3000万人的死亡率数据的联系，在所有四个英国国家建立了前瞻性队列。在我们的初步分析中，我们纳入了接受BNT 162 b2（tozinameran; Pfizer-BioNTech）或ChAdOx 1 nCoV-19（Oxford-AstraZeneca）疫苗初次接种的个体。然后，我们将分析限制在那些给予BNT 162 b2或mRNA-1273（elasomeran; Moderna）加强剂并在2021年12月20日至2022年2月28日期间（当omicron（B.1.1.529）变体占主导地位时）具有严重COVID-19结果的人。我们拟合了时间依赖性泊松回归模型，并计算了风险因素与COVID-19相关住院或死亡之间相关性的校正率比（aRR）和95% CI。我们调整了一系列潜在的协变量，包括年龄、性别、合并症和既往SARS-CoV-2感染。按疫苗类型进行分层分析。然后，我们使用固定效应荟萃分析在英国国家进行了汇总分析。在2020年12月8日至2022年2月28日期间，有16，208，600人完成了他们的主要疫苗接种计划，13，836，390人接受了加强剂量。 在2021年12月20日至2022年2月28日期间，59510人（0.4%）的初级疫苗组和26100人（0.2%）的接受加强疫苗的人出现了严重的COVID-19结果。 接受加强剂后，严重COVID-19结局的风险降低（发生率变化：每1000人年8.8起事件至每1000人年7.6起事件）。老年人（≥80岁vs 18-49岁; aRR 3·60 [95% CI 3·45-3·75]），合并症患者（≥5种合并症vs无合并症; 9·51 [9·07-9·97]），男性（男性vs女性; 1·23 [1·20-1·26]），以及有某些潜在健康状况的患者，特别是接受免疫抑制剂治疗的患者（是vs否; 5.80 [5.53 - 6.09]）-慢性肾病患者（5期vs否; 3.71 [2.90 - 4.74]）尽管接受了初始加强治疗，但仍处于高风险状态。有COVID-19感染史的个体风险降低（加强剂量前感染≥9个月vs既往无感染; aRR 0.41 [95% CI 0.29 - 0.58]）。老年人、多发性硬化症患者和有特定基础健康状况的人在初始疫苗加强剂后，COVID-19住院和死亡的风险仍然增加，因此应优先考虑额外的加强剂，包括新的优化版本和不断增加的COVID-19治疗方法。国家核心免疫学、英国研究与创新（医学研究理事会）、英国健康数据研究、苏格兰政府和爱丁堡大学。
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. 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. 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]). 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. National Core Studies–Immunity, UK Research and Innovation (Medical Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.