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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

See all articles by Tommy Nyberg

Tommy Nyberg

University of Cambridge - MRC Biostatistics Unit

Neil M. Ferguson

Imperial College London - MRC Centre for Global Infectious Disease Analysis

Sophie G. Nash

UK Health Security Agency - COVID-19 National Epidemiology Cell

Harriet H. Webster

UK Health Security Agency - COVID-19 National Epidemiology Cell

Seth Flaxman

University of Oxford - Department of Computer Science

Nick Andrews

Public Health England Colindale; UK Health Security Agency - COVID-19 Surveillance Cell

Wes Hinsley

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics

Jamie Lopez Bernal

Public Health England Colindale; UK Health Security Agency - COVID-19 Surveillance Cell

Meaghan Kall

Public Health England Colindale; UK Health Security Agency - COVID-19 National Epidemiology Cell

Samir Bhatt

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics

Paula Bianca Blomquist

Public Health England - National Infection Service; UK Health Security Agency - Outbreak Surveillance Team

Asad Zaidi

Government of the United Kingdom - Public Health England; UK Health Security Agency - COVID-19 National Epidemiology Cell

Erik Volz

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics

Nurin Abdul Aziz

Public Health England - National Infection Service; UK Health Security Agency - COVID-19 National Epidemiology Cell

Katie Harman

UK Health Security Agency - COVID-19 National Epidemiology Cell

Russell Hope

Public Health England ; UK Health Security Agency - COVID-19 National Epidemiology Cell

Andre Charlett

Public Health England Colindale; UK Health Security Agency - Statistics, Modelling and Economics Department

Meera A. Chand

Public Health England Colindale; UK Health Security Agency - COVID-19 Genomics Cell

Azra Ghani

Imperial College London - MRC Centre for Global Infectious Disease Analysis; Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics

Shaun Seaman

University of Cambridge - MRC Biostatistics Unit

Gavin Dabrera

UK Health Security Agency - COVID-19 National Epidemiology Cell

Daniela DeAngelis

Government of the United Kingdom - Public Health England; University of Cambridge - MRC Biostatistics Unit

Anne M. Presanis

University of Cambridge - MRC Biostatistics Unit

Simon Thelwall

Government of the United Kingdom - Public Health England; UK Health Security Agency - COVID-19 National Epidemiology Cell

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

Nyberg, Tommy and Ferguson, Neil M. and Nash, Sophie G. and Webster, Harriet H. and Flaxman, Seth and Andrews, Nick and Hinsley, Wes and Bernal, Jamie Lopez and Kall, Meaghan and Bhatt, Samir and Blomquist, Paula Bianca and Zaidi, Asad and Volz, Erik and Abdul Aziz, Nurin and Harman, Katie and Hope, Russell and Charlett, Andre and Chand, Meera A. and Ghani, Azra and Seaman, Shaun and Dabrera, Gavin and DeAngelis, Daniela and Presanis, Anne M. and Thelwall, Simon, 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. Available at SSRN: https://ssrn.com/abstract=4025932 or http://dx.doi.org/10.2139/ssrn.4025932

Tommy Nyberg

University of Cambridge - MRC Biostatistics Unit ( email )

Cambridge
United Kingdom

Neil M. Ferguson (Contact Author)

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Sophie G. Nash

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Harriet H. Webster

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Seth Flaxman

University of Oxford - Department of Computer Science ( email )

Wolfson Building, Parks Road
Oxford
United Kingdom

Nick Andrews

Public Health England Colindale ( email )

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

UK Health Security Agency - COVID-19 Surveillance Cell ( email )

United Kingdom

Wes Hinsley

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics ( email )

London
United Kingdom

Jamie Lopez Bernal

Public Health England Colindale ( email )

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

UK Health Security Agency - COVID-19 Surveillance Cell ( email )

United Kingdom

Meaghan Kall

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Samir Bhatt

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics ( email )

London
United Kingdom

Paula Bianca Blomquist

Public Health England - National Infection Service

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

UK Health Security Agency - Outbreak Surveillance Team ( email )

United Kingdom

Asad Zaidi

Government of the United Kingdom - Public Health England ( email )

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Erik Volz

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics ( email )

London
United Kingdom

Nurin Abdul Aziz

Public Health England - National Infection Service ( email )

United Kingdom

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Katie Harman

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Russell Hope

Public Health England ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Andre Charlett

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

UK Health Security Agency - Statistics, Modelling and Economics Department ( email )

United Kingdom

Meera A. Chand

Public Health England Colindale ( email )

61 Colindale Avenue
London, NW9 5EQ
United Kingdom

UK Health Security Agency - COVID-19 Genomics Cell ( email )

United Kingdom

Azra Ghani

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics ( email )

London
United Kingdom

Shaun Seaman

University of Cambridge - MRC Biostatistics Unit ( email )

Cambridge
United Kingdom

Gavin Dabrera

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

Daniela DeAngelis

Government of the United Kingdom - Public Health England ( email )

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

University of Cambridge - MRC Biostatistics Unit ( email )

Cambridge
United Kingdom

Anne M. Presanis

University of Cambridge - MRC Biostatistics Unit ( email )

United Kingdom

Simon Thelwall

Government of the United Kingdom - Public Health England ( email )

Wellington House
133-155 Waterloo Road
London, SE1 8UG
United Kingdom

UK Health Security Agency - COVID-19 National Epidemiology Cell ( email )

London
United Kingdom

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