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Cited by 191SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesCOVID-19 epidemiological studies

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February

Open access
Grint, Daniel J, Wing, Kevin, Williamson, Elizabeth, McDonald, Helen I, Bhaskaran, Krishnan, Evans, David, Evans, Stephen JW, Walker, Alex J +28 more·2021·Eurosurveillance
DOI 10.2807/1560-7917.es.2021.26.11.2100256PMC PMC7976383

Published version of a preprint

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Abstract

The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34–2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.

AI snapshot

Written from the paper’s full text.

TL;DR

In England, infection with the SARS-CoV-2 B.1.1.7 variant of concern (VOC) was associated with a higher risk of death than non-VOC infection after adjustment for demographics and comorbidities (HR: 1.67; 95% CI: 1.34–2.09). Absolute 28-day death risk increased with age and comorbidities and was consistently higher for VOC across strata.

Key findings

  • In a fully adjusted Cox model, VOC infection was associated with two-thirds higher hazard of death compared with non-VOC (HR: 1.67; 95% CI: 1.34–2.09; p < 0.0001); a sensitivity analysis restricted to people testing positive at least 28 days before censoring gave HR: 1.71 (95% CI: 1.36–2.15; p < 0.0001).
  • In a fully adjusted logistic model, VOC was associated with increased odds of death by 28 days (adjusted odds ratio: 1.73; 95% CI: 1.34–2.23; p < 0.0001). Absolute risk was higher for VOC across age, sex, and comorbidity strata; the highest risk was among those aged ≥85 years with two or more comorbidities (VOC: males 24.3%, females 14.7%; non-VOC: males 16.7%, females 9.7%).
  • Among 184,786 people with known spike gene target failure (SGTF) status, there were 867 deaths (419 VOC; 448 non-VOC). The VOC group was younger and had fewer comorbidities, and median follow-up was shorter for VOC (36 days; IQR: 30–45) than non-VOC (57 days; IQR: 40–72).
  • Increased hazards for VOC were consistent across all pre-specified subgroup analyses, including epidemiological week, age group, number of comorbidities, ethnicity, and index of multiple deprivation quintile.

Methods

  • Data came from the OpenSAFELY electronic health records platform covering 40% of England’s population registered with a general practitioner, with linked GP, SARS-CoV-2 testing, vaccination, and mortality records. Cases were people testing positive for SARS-CoV-2 between 16 November 2020 and 11 January 2021, followed until death or censoring on 5 February 2021; vaccinations and diagnoses before the study period were exclusion criteria. SGTF status was known for 184,786 of 441,161 (42%) confirmed infections (91,775 VOC; 93,011 non-VOC).
  • Relative hazard of death was estimated using a Cox proportional hazards regression model stratified by upper tier local authority, with follow-up from positive test and censoring on 5 February 2021 or 7 days before vaccination. Absolute risk of death by 28 days was estimated from marginal means of a fully adjusted logistic regression model restricted to 112,979 people diagnosed at least 28 days before the censoring date, with deaths beyond 28 days censored.

Limitations

  • The paper states that people with asymptomatic or mild infection may not present for testing, so estimates of absolute risk of death by 28 days may overestimate the true case fatality ratio. It also states that SARS-CoV-2 tests performed in hospital settings in the UK are not tested for PCR S-gene target failure and are therefore not included.
  • Evident from the text: SGTF status was known for only 42% of confirmed SARS-CoV-2 infections in the study period, so the analysed population may not represent all cases. The VOC group also had shorter median follow-up than the non-VOC group, although the sensitivity analysis restricted to at least 28 days from testing to censoring was consistent.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.2807/1560-7917.es.2021.26.11.2100256

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 12 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In a fully adjusted logistic regression model restricted to people diagnosed at least 28 days before censoring, VOC was associated with increased odds of death by 28 days compared with non-VOC (AOR 1.73; 95% CI 1.34-2.23; p < 0.0001).

    “Consistent with the Cox model above, VOC was associated with increased odds of death in this model (adjusted odds ratio (AOR): 1.73; 95% CI: 1.34–2.23; p value < 0.0001, vs non-VOC).”
    Quote in the paperSubstantial claim
  • Findingown data

    The highest risk of death within 28 days was among people aged 85 years and older with two or more comorbidities: VOC males 24.3%, VOC females 14.7%, non-VOC males 16.7%, non-VOC females 9.7%.

    “The highest risk of death within 28 days was seen among those 85 years and older with two or more comorbidities: VOC: males 24.3%; females: 14.7%; non-VOC: males: 16.7%; females: 9.7%).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The risk of death by 28 days was consistently higher for male cases than female cases.

    “The risk of death was consistently higher for male cases and increased with age and the presence of comorbidities.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In a sensitivity analysis restricted to people testing positive for SARS-CoV-2 at least 28 days before the censoring date, the hazard ratio for death with VOC versus non-VOC was 1.71 (95% CI 1.36-2.15; p < 0.0001).

    “in an analysis restricted to people testing positive for SARS-CoV-2 infection a minimum of 28 days before the censoring date, the hazard ratio was 1.71 (95% CI: 1.36–2.15; p < 0.0001).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In England, infection with the SARS-CoV-2 VOC B.1.1.7 was associated with a two-thirds higher hazard of death compared with non-VOC infection in a fully adjusted analysis accounting for demographics and comorbidities (HR 1.67; 95% CI 1.34-2.09; p < 0.0001).

    “We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34–2.09; p < 0.0001).”
    • Also stated in: § Relative hazard of death · plain
      “In a fully adjusted analysis accounting for demographics and comorbidities, hazards were two-thirds higher in the VOC group (hazard ratio (HR): 1.67; 95% confidence interval (CI): 1.34–2.09; p < 0.0001) compared with non-VOC (Figure 1).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The non-VOC comparison group represents infection with the previously circulating SARS-CoV-2 virus.
    • Rests on an assumption: The proportional hazards assumption of the Cox regression model holds.
  • May combine two claims. 7
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    Among people younger than 65 years without comorbidities, the risk of death by 28 days was low and was higher for male than female cases (VOC: males 0.14%, females 0.07%; non-VOC: males 0.09%, females 0.05%).

    “The risk of death was low for people younger than 65 years in the absence of comorbidities; in this age group it was higher for male than female cases (VOC: males: 0.14%; females: 0.07% vs non-VOC: males: 0.09%; females: 0.05%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Absolute risk of death by 28 days after a SARS-CoV-2-positive test increased with age and with the presence of comorbidities.

    “Absolute risk of death by 28 days increased with age and comorbidities.”
    • Also stated in: § Absolute risk of death by 28 days · plain
      “The risk of death was consistently higher for male cases and increased with age and the presence of comorbidities.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The logistic regression model for absolute risk of death by 28 days was fully adjusted for age, sex, index of multiple deprivation, ethnicity, smoking status, obesity, household size, NHS England region, rural/urban classification, comorbidities, epidemiological week and care home status.

    “The fully adjusted model includes adjustment for: age, sex, index of multiple deprivation, ethnicity, smoking status, obesity, household size, NHS England region, rural/urban classification, comorbidities, epidemiological week and care home status.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The effects of age and comorbidities on mortality appear to be collinear, as adjustment for comorbidities did not alter the findings after adjustment for age.

    “Interestingly, the effects of age and comorbidities appear to be collinear as adjustment for comorbidities did not alter the findings after adjustment for age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The VOC is the dominant strain throughout the UK and is increasing in prevalence across Europe.

    “It is now the dominant strain throughout the UK and is increasing in prevalence across Europe [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] European Centre for Disease Prevention and Control (ECDC). SARS-CoV-2 - increased circulation of variants of concern and vaccine rollout in the EU/EEA,14th update. Stockholm: ECDC; 2021. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/RRA-covid-19-14th-update-15-feb-2021.pdf

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Unmitigated spread of the B.1.1.7 VOC has the potential to be both faster and more deadly than the pandemic to date.

    “Unmitigated spread of the B.1.1.7 VOC has the potential to be both faster and more deadly than the pandemic to date.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In the UK, all-cause death by 28 days after confirmation of SARS-CoV-2 infection is the standard definition of SARS-CoV-2 mortality.

    “In the UK, all-cause death by 28 days after confirmation of SARS-CoV-2 infection is the standard definition of SARS-CoV-2 mortality [12], so we used death from any cause as the primary outcome.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Department of Health and Social Care. New UK-wide methodology agreed to record COVID-19 deaths. London: Department of Health and Social Care; 2020. Available from: https://www.gov.uk/government/news/new-uk-wide-methodology-agreed-to-record-covid-19-deaths

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Spike gene target failure (SGTF) is a proxy for VOC identification, with greater than 95% sensitivity for VOC diagnosis during the period from 16 November to 11 January.

    “Spike gene target failure (SGTF) is therefore a proxy for VOC identification, with greater than 95% sensitivity for VOC diagnosis during the period from 16 November to 11 January [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Public Health England (PHE). Investigation of novel SARS-CoV-2 variant. Variant of concern 20201/01. London: PHE. [Accessed: 25 Feb 2021]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/959438/Technical_Briefing_VOC_SH_NJL2_SH2.pdf

      Not checked in the free run.

    • Rests on an assumption: A test result without spike gene target failure indicates non-VOC infection.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The relative hazard of death for VOC versus non-VOC was estimated using a Cox proportional hazards regression model stratified by region (upper tier local authority area).

    “We calculated the relative hazard of death for VOC compared with non-VOC cases using a Cox proportional hazards regression model stratified by region (upper tier local authority area (UTLA)) [4,5].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Cox, 1972, Regression models and life‐tables., J R Stat Soc B source

      Not checked in the free run.

    • cites [5] Cox DR, Oakes D. Analysis of survival data. London: CRC press; 1984. ISBN 9780412244902.

      Not checked in the free run.

    • Rests on an assumption: The proportional hazards assumption of the Cox regression model holds.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    SARS-CoV-2 tests performed in hospital settings in the UK are not tested for PCR S-gene target failure and are therefore not included in this analysis.

    “In addition, SARS-CoV-2 tests performed in hospital settings in the UK are not tested for PCR S-gene target failure and are therefore not included.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The SARS-CoV-2 VOC B.1.1.7 is more transmissible than previously circulating forms (non-VOC).

    “Early analysis suggests it is more transmissible than previously circulating forms (non-VOC) [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Davies, 2021, Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England., Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Emerging data suggest that the currently approved vaccines for SARS-CoV-2 are effective against the B.1.1.7 VOC.

    “Crucially, emerging data suggest that the currently approved vaccines for SARS-CoV-2 are effective against the B.1.1.7 VOC [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Public Health England (PHE). PHE monitoring of the effectiveness of COVID-19 vaccination. London: PHE; 2021. Available from: https://www.gov.uk/government/publications/phe-monitoring-of-the-effectiveness-of-covid-19-vaccination

      Not checked in the free run.

12 of 12

  • The paper relies on this without support.

    The non-VOC comparison group represents infection with the previously circulating SARS-CoV-2 virus.

    “We found that this VOC was associated with two-thirds higher case fatality than the previously circulating virus in this unvaccinated population.”

  • The paper relies on this without support.

    The proportional hazards assumption of the Cox regression model holds.

    “using a Cox proportional hazards regression model stratified by region (upper tier local authority area (UTLA)) [4,5]”

  • The paper relies on this without support.

    The study population, drawn from the OpenSAFELY platform covering 40% of England's population registered with a GP, is representative of the wider population of England.

    “Data were drawn from the OpenSAFELY electronic health records secure research platform, covering 40% of England’s population registered with a general practitioner (GP) (see Supplement, part 1).”

  • The paper relies on this without support.

    A test result without spike gene target failure indicates non-VOC infection.

    “Spike gene target failure (SGTF) is therefore a proxy for VOC identification, with greater than 95% sensitivity for VOC diagnosis during the period from 16 November to 11 January [3].”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • VOC and non-VOC case counts are reversed in the text

    Minor

    The study-population paragraph assigns 91,775 cases to VOC and 93,011 to non-VOC, while Table 1 assigns those counts to non-VOC and VOC, respectively.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Cox DR, Oakes D. Analysis of survival data. London: CRC press; 1984. ISBN 9780412244902.

Cited by

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Related

Authors
Grint, D. J., Wing, K., Williamson, E., McDonald, H. I., Bhaskaran, K., Evans, D., Evans, S. J., Walker, A. J., Hickman, G., Nightingale, E., Schultze, A., Rentsch, C. T., Bates, C., Cockburn, J., Curtis, H. J., Morton, C. E., Bacon, S., Davy, S., Wong, A. Y., Mehrkar, A., Tomlinson, L., Douglas, I. J., Mathur, R., Blomquist, P., MacKenna, B., Ingelsby, P., Croker, R., Parry, J., Hester, F., Harper, S., DeVito, N. J., Hulme, W., Tazare, J., Goldacre, B., Smeeth, L., & Eggo, R. M.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • University of Oxford (GB)
  • The Phoenix Partnership (TPP), TPP House, Leeds, United Kingdom
  • The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
  • Public Health England (GB)
Corresponding author
Grint, Daniel J
ORCID
Venue
Eurosurveillance
Publisher
European Centre for Disease Control and Prevention (ECDC)
Published
2021-03-18
Volume
26
Issue
11
ISSN
  • 1025-496X (ISSN-L)
  • 1560-7917
DOI
10.2807/1560-7917.es.2021.26.11.2100256
PMC
PMC7976383
OpenAlex
W3136104126
Cited by
189
References
8
Citations by year
2026: 1 · 2025: 3 · 2024: 13 · 2023: 18 · 2022: 68 · 2021: 85 · 2020: 1
FWCI
14.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Eurosurveillance (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • National Institute for Health and Care Research ((NIHR200908), MR/S003975/1, MR/V015737/1, MR/V015737)
  • Medical Research Council (MR/S003975/1, 19065, MR/R010161/1, MR/V015737/1, NIHR200908, MC_PC_19065)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Keywords
SARS-CoV-2, B.1.1.7 variant, variants of concern, case fatality, COVID-19 mortality, disease severity, comorbidities, age, hazard ratio, England
MeSH terms
COVID-19, SARS-CoV-2, Age Factors, England, Humans, Comorbidity

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