Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
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DOI：
10.1016/s0140-6736(22)00462-7
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发表时间：
2022-04-02
期刊：
影响因子：
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通讯作者：
Thelwall S
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文献类型：
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作者：
Nyberg T;Ferguson NM;Nash SG;Webster HH;Flaxman S;Andrews N;Hinsley W;Bernal JL;Kall M;Bhatt S;Blomquist P;Zaidi A;Volz E;Aziz NA;Harman K;Funk S;Abbott S;COVID-19 Genomics UK (COG-UK) consortium;Hope R;Charlett A;Chand M;Ghani AC;Seaman SR;Dabrera G;De Angelis D;Presanis AM;Thelwall S
SARS-CoV-2的omicron变异体（B.1.1.529）已经证明了部分疫苗逃逸和高传播性，早期研究表明感染的严重程度低于delta变异体（B.1.617.2）。我们的目的是通过在一个大型的国家队列中评估住院、入院或死亡的相对风险，来改善相对于delta的心血管事件严重程度。2021年11月29日至2022年1月9日期间居住在英格兰的实验室确诊COVID-19病例的个人数据与疫苗接种状态、住院和死亡率的常规数据集相关联。使用比例风险回归估计确诊感染后14天内住院或入院或28天内死亡的相对风险。按检测日期、10岁年龄段、种族、居住地区和疫苗接种状态对分析进行分层，并进一步调整性别、多重剥夺十分位数指数、既往感染证据和每个年龄段内的年龄。二次分析估计了变异特异性和疫苗特异性疫苗的有效性以及与delta相比omicron感染的内在相对严重程度（即未接种疫苗病例的相对风险）。omicron与delta相比，住院（不一定导致入院）的校正风险比（HR）为0.56（95% CI 0.54 - 0.58）;住院和死亡的HR估计值分别为0.41（0.39 - 0.43）和0.31（0.26 - 0.37）。对于检查的所有终点，Omicron与Δ HR估计值随年龄变化。在10岁以下的患者中，住院的校正HR为1·10（0·85-1·42），在60-69岁的患者中降至0·25（0·21-0·30），然后在80岁以上的患者中增至0·47（0·40-0·56）。对于这两种变种，过去的感染在接种疫苗（HR 0.47 [0.32 - 0.68]）和未接种疫苗（0.18 [0.06 - 0.57]）的病例中都对死亡有一定的保护作用。在接种疫苗的病例中，既往感染除了疫苗接种提供的保护外，对住院没有提供额外的保护（HR 0.96 [0.88 - 1.04]）;然而，对于未接种疫苗的病例，既往感染提供了中度保护（HR 0.55 [0.48 - 0.63]）。未接种疫苗病例的Omicron与Δ HR估计值（0·30 [0·28-0·32]）低于主要分析中所有病例的相应HR估计值。在omicron病例中，使用mRNA疫苗进行加强接种对住院和死亡具有高度保护作用（加强接种后8-11周与未接种疫苗的住院HR：0·22 [0·20-0·24]），加强接种后提供的保护不受第1剂和第2剂疫苗的影响。在SARS-CoV-2感染后，Omicron组的严重结局风险显著低于Delta组，更严重终点的风险降低更高，且随年龄变化显著。观察到的风险的基础是内在严重程度（未接种疫苗的个体）的较大降低，与疫苗有效性的降低相抵消。有记录的既往SARS-CoV-2感染为未接种疫苗的个体提供了一定的住院保护和高度的死亡保护，但仅为接种疫苗的个体提供了死亡终点的额外保护。使用mRNA疫苗的加强疫苗接种在突破性确诊的omicron感染中保持超过70%的住院和死亡保护。医学研究理事会、英国研究与创新部、卫生与社会保健部、国家卫生研究所、Community Jameel以及工程与物理科学研究理事会。
The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort. Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases). The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32–0·68]) and unvaccinated (0·18 [0·06–0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88–1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48–0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28–0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [0·20–0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2. The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections. Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.