Download This Paper
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.
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
29 Pages Posted: 4 Feb 2022
More...Abstract
Background: 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 compared with Delta (B.1.617.2). We sought 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 22 November 2021 and 9 January 2022 were linked to routine datasets on vaccination status, hospitalisation and mortality. The relative risk of attendance at hospital within 14 days, or death within 28 days following confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, region and vaccination status and further adjusted for sex, index of multiple deprivation decile, evidence of a prior infection and year of age within each age band. A secondary analysis estimated variant- and vaccine-specific vaccine effectiveness and the intrinsic relative severity of Omicron infection compared with Delta; i.e. the relative risk in unvaccinated cases.
Findings: We found that 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 the estimates were 0.41 (95%CI: 0.39-0.43) and 0.31 (95%CI: 0.26-0.37), respectively. Omicron vs Delta HR estimates varied with age for all endpoints examined: the adjusted HR for hospital admission was 1.07 (95%CI: 0.83-1.38) in <10 year-olds, falling to 0.25 (95%CI: 0.21-0.30) in 60-69 year-olds, and rising to 0.48 (95%CI: 0.40-0.57) in ≥80 year-olds. For both variants, past infection gave some protection against death both in vaccinated (HR: 0.45 [95%CI: 0.30-0.68]) and unvaccinated (0.14 [95%CI: 0.04-0.45]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR: 0.99 [95%CI: 0.9-1.08]), whilst for unvaccinated cases moderate protection remained (HR: 0.53 [95%CI: 0.46-0.61]). Estimation of variant-specific vaccine effectiveness gave lower Omicron vs Delta HR estimates for hospital admission (0.29 [95%CI: 0.28-0.31]) in unvaccinated cases than 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, compared with unvaccinated: 0.22 [95%CI: 0.19-0.24]), with the protection afforded after a booster not being significantly 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 compared with Delta cases, with higher reductions for more severe endpoints and significant variation with age. The (low) risk of hospital admission in children <10 years of age did not differ significantly by variant, while 60-69 year-olds had an approximately 75% reduced risk of hospital admission with Omicron compared with Delta. Underlying the observed HRs is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. A documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvac
Funding: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research and Community Jameel, Engineering and Physical Sciences Research Council.
Declaration of Interest: None to declare.
Ethical Approval: Ethics permission was sought for analyses of these data via Imperial College London’s standard ethical review processes and the study was approved by the College’s Research Governance and Integrity Team (ICREC reference: 21IC6945).
Keywords: SARS-CoV-2, COVID-19, variant of concern, Omicron, Delta, severity, hospitalisation, death, observational study
Suggested Citation: Suggested Citation