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dc.contributor.authorNyberg, Tommy
dc.contributor.authorFerguson, Neil M
dc.contributor.authorNash, Sophie G
dc.contributor.authorWebster, Harriet H
dc.contributor.authorFlaxman, Seth
dc.contributor.authorAndrews, Nick
dc.contributor.authorHinsley, Wes
dc.contributor.authorBernal, Jamie Lopez
dc.contributor.authorKall, Meaghan
dc.contributor.authorBhatt, Samir
dc.contributor.authorBlomquist, Paula
dc.contributor.authorZaidi, Asad
dc.contributor.authorVolz, Erik
dc.contributor.authorAziz, Nurin Abdul
dc.contributor.authorHarman, Katie
dc.contributor.authorFunk, Sebastian
dc.contributor.authorAbbott, Sam
dc.contributor.authorCOVID-19 Genomics UK (COG-UK) consortium
dc.contributor.authorHope, Russell
dc.contributor.authorCharlett, Andre
dc.contributor.authorChand, Meera
dc.contributor.authorGhani, Azra C
dc.contributor.authorSeaman, Shaun
dc.contributor.authorDabrera, Gavin
dc.contributor.authorDe Angelis, Daniela
dc.contributor.authorPresanis, Anne
dc.contributor.authorThelwall, Simon
dc.date.accessioned2022-02-26T00:30:35Z
dc.date.available2022-02-26T00:30:35Z
dc.date.issued2022-04-02
dc.identifier.issn0140-6736
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334466
dc.description.abstractBACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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.
dc.description.sponsorshipUKRI Medical Research Council (MRC) ([MR/R015600/1]; [Unit Programme number MC/UU/00002/11]; [Unit Programme number MC/UU/00002/10]); MRC UKRI/DHSC NIHR COVID-19 rapid response call ([MR/V038109/1]; [MC/PC/19074]); NIHR Health Protection Units in: Modelling and Health Economics, Behavioural Science and Evaluation, Respiratory Infections; the NIHR Cambridge Biomedical Research Centre ([BRC-1215-20014]); Wellcome Trust ([210758/Z/18/Z]); Community Jameel; UKRI Engineering and Physical Sciences Research Council.
dc.publisherElsevier BV
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleComparative 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.
dc.typeArticle
dc.publisher.departmentMrc Biostatistics Unit
dc.date.updated2022-02-25T14:17:42Z
prism.publicationNameLancet
dc.identifier.doi10.17863/CAM.81883
dcterms.dateAccepted2022-02-25
rioxxterms.versionofrecord10.1016/S0140-6736(22)00462-7
rioxxterms.versionAM
dc.contributor.orcidNyberg, Tommy [0000-0002-9436-0626]
dc.contributor.orcidSeaman, Shaun [0000-0003-3726-5937]
dc.contributor.orcidDe Angelis, Daniela [0000-0001-6619-6112]
dc.contributor.orcidPresanis, Anne [0000-0003-3078-4427]
dc.identifier.eissn1474-547X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idMRC (MC_PC 19074)
pubs.funder-project-idNational Institute for Health Research (NIHR) (via University of Bristol) (200877 2020 - 245)
pubs.funder-project-idMRC (MC_PC_19027)
cam.orpheus.successWed Mar 23 10:26:37 GMT 2022 - Embargo updated
cam.depositDate2022-02-25
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-09-30


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