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 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.
Bibliographical noteFunding Information: This work was supported by grants from the UK Research and Innovation (UKRI) Medical Research Council (NMF, WH, SB, EV, ACG [Centre for Global Infectious Disease Analysis; MR/R015600/1], DDA, AMP [MC/UU/00002/11], and SRS [MC/UU/00002/10]); Medical Research Council UKRI–Department of Health and Social Care National Institute for Health Research (NIHR) COVID-19 rapid response call (NMF, SB [MR/V038109/1], TN, AC, DDA, and AMP [MC/PC/19074]); the NIHR Health Protection Units in: Modelling and Health Economics (NMF, WH, SB, EV, AC, and ACG [NIHR200908]), Behavioural Science and Evaluation (AC and DDA), and Respiratory Infections (JLB); Wellcome Trust (SFunk and SA [210758/Z/18/Z]); philanthropic funding from Community Jameel (NMF, WH, SB, and EV); and the UKRI Engineering and Physical Sciences Research Council (SFlax [EP/V002910/2]). The funders played no direct role in the study. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
GD declares that his employer UK Health Security Agency (previously operating as Public Health England) received funding from GlaxoSmithKline for a research project related to influenza antiviral treatment. This preceded and had no relation to COVID-19, and GD had no role in and received no funding from the project. All other authors declare no competing interests.
Open Access: This is an Open Access article under the CC BY 4.0 license.
Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd.
Citation: Tommy Nyberg, Neil M Ferguson, Sophie G Nash, Harriet H Webster, Seth Flaxman, Nick Andrews, Wes Hinsley, Jamie Lopez Bernal, Meaghan Kall, Samir Bhatt, Paula Blomquist, Asad Zaidi, Erik Volz, Nurin Abdul Aziz, Katie Harman, Sebastian Funk, Sam Abbott, Tommy Nyberg, Neil M Ferguson, Sophie G Nash, Harriet H Webster, Seth Flaxman, Nick Andrews, Wes Hinsley, Jamie Lopez Bernal, Meaghan Kall, Samir Bhatt, Paula Blomquist, Asad Zaidi, Erik Volz, Nurin Abdul Aziz, Katie Harman, Sebastian Funk, Sam Abbott, Russell Hope, Andre Charlett, Meera Chand, Azra C Ghani, Shaun R Seaman, Gavin Dabrera, Daniela De Angelis, Anne M Presanis, Simon Thelwall, Russell Hope, Andre Charlett, Meera Chand, Azra C Ghani, Shaun R Seaman, Gavin Dabrera, Daniela De Angelis, Anne M Presanis, Simon Thelwall,
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,
The Lancet, Volume 399, Issue 10332, 2022, Pages 1303-1312, ISSN 0140-6736.