COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.
COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.
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英格兰医疗工人的COVID-19疫苗覆盖范围以及BNT162B2 mRNA疫苗对感染的有效性（Siren）：一项前瞻性，多中心，队列研究。
DOI：
10.1016/s0140-6736(21)00790-x
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发表时间：
2021-05-08
期刊：
影响因子：
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通讯作者：
SIREN Study Group
中科院分区：
文献类型：
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作者：
Hall VJ;Foulkes S;Saei A;Andrews N;Oguti B;Charlett A;Wellington E;Stowe J;Gillson N;Atti A;Islam J;Karagiannis I;Munro K;Khawam J;Chand MA;Brown CS;Ramsay M;Lopez-Bernal J;Hopkins S;SIREN Study Group
自2020年12月起，英国迅速推出了BNT162b2 mRNA和ChAdOx1 nCOV-19腺病毒载体疫苗。我们的目的是确定与两种疫苗的疫苗覆盖率相关的因素，并在一组接受定期无症状检测的卫生保健工作者中记录BNT162b2 mRNA疫苗的疫苗有效性。SIREN研究是一项在英国公立医院工作的员工（年龄≥18岁）中进行的前瞻性队列研究。在随访开始时，参与者被分配到阳性队列（抗体阳性或感染史[由既往抗体或PCR检测阳性表明]）或阴性队列（抗体阴性，无既往阳性检测）。在入组时收集基线危险因素，每2周收集一次症状状况，并通过与国家免疫管理系统和问卷的联系收集疫苗接种状况。参与者每两周进行无症状SARS-CoV-2 PCR检测和每月进行抗体检测，并捕获SIREN以外的所有检测（包括症状检测）。该分析的数据截止日期为2021年2月5日。随访期为2020年12月7日至2021年2月5日。主要结局是接种疫苗的参与者（曾接种疫苗的二元变量；由两个疫苗接种数据源中的至少一个记录的至少一次疫苗剂量表示）用于疫苗覆盖率分析，以及通过PCR检测确认的SARS-CoV-2感染用于疫苗有效性分析。我们进行了混合效应逻辑回归分析，以确定与疫苗覆盖率相关的因素。我们使用了一个分段指数危险混合效应模型（共享脆弱型模型），使用泊松分布来计算风险比，以比较未接种疫苗和接种疫苗的参与者的感染时间，并估计BNT162b2疫苗对所有pcr阳性感染（无症状和有症状）的影响。本研究已在ISRCTN注册，编号为ISRCTN11041050，正在进行中。来自104个地点（全部在英格兰）的23324名参与者符合本分析的纳入标准并被纳入。纳入的参与者中位年龄为46.1岁（IQR为36.0 - 54.1），女性为19692人（84%）；在分析期开始时，8203人（35%）被分配到阳性队列，15121人（65%）被分配到阴性队列。总随访时间为2个日历月1 106 905人日（接种疫苗396 318人，未接种疫苗710 587人）。2021年2月5日，疫苗覆盖率为89%，其中94%接种了BNT162b2疫苗。较低的覆盖率与既往感染、性别、年龄、种族、工作角色和多重剥夺指数得分有关。在随访期间，未接种疫苗的队列中有977例新感染，发病率密度为每1万人日14例感染；接种疫苗的队列在第一次接种后21天或更长时间内发生了71例新感染（发病率密度为每1万人日8例感染），在第二次接种后7天发生了9例感染（发病率密度为每1万人日4例感染）。在未接种疫苗的队列中，543名（56%）参与者有典型的COVID-19症状，140名（14%）参与者在PCR阳性检测日期前或14天无症状，而在接种疫苗的队列中，有29名（36%）参与者有典型的COVID-19症状，15名（19%）参与者无症状。在研究人群中，单剂BNT162b2疫苗在首次接种后21天的疫苗有效性为70% (95% CI 55-85)，在两次接种后7天的疫苗有效性为85%（74-96）。我们的研究结果表明，BNT162b2疫苗可以预防有症状和无症状的工作年龄成人感染。当流行的主要变异为B1.1.7时，该队列接种疫苗，并显示出对该变异的有效性。英国公共卫生部、英国卫生和社会保障部以及国家卫生研究所。
BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.