Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7

CMMID COVID-19 Working Group; Nicholas G. Davies; Christopher I. Jarvis; William Waites

doi:10.1038/s41586-021-03426-1

Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7

CMMID COVID-19 Working Group, Nicholas G. Davies^*, Christopher I. Jarvis, William Waites

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

681 Citations (Scopus)

Abstract

SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 2020¹, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity². Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)¹). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.

Original language	English
Pages (from-to)	270-274
Number of pages	5
Journal	Nature
Volume	593
Issue number	7858
Early online date	15 Mar 2021
DOIs	https://doi.org/10.1038/s41586-021-03426-1
Publication status	Published - 13 May 2021

Funding

Acknowledgements We gratefully acknowledge the assistance of Public Health England in providing the analysis data and authorizing the release of an anonymized dataset. This work was supported by grants from UK Research and Innovation, the National Institutes of Health Research (NIHR) Health Protection Research Unit in Immunisation (NIHR200929) and the UK Medical Research Council (MC_PC_19065) (N.G.D.); Global Challenges Research Fund project ‘RECAP’ managed through Research Councils UK and the Economic and Social Research Council (ES/P010873/1) (C.I.J.); European Commission project ‘EpiPose’ (101003688) and the NIHR (NIHR200908) (W.J.E.); the National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01AI148127) (N.P.J.); a Royal Society-Wellcome Trust Sir Henry Dale Fellowship (218554/Z/19/Z) (K.D.-O.); and a UKRI Future Leaders Fellowship (MR/S017968/1) (R.H.K.). See Supplementary Note 2 for working group acknowledgements.

Keywords

SARS CoV-2
PCR tests
mortality

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10.1038/s41586-021-03426-1

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@article{c53acc5c703f49848fa3bc29dec77851,

title = "Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7",

abstract = "SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.",

keywords = "SARS CoV-2, PCR tests, mortality",

author = "{CMMID COVID-19 Working Group} and Davies, {Nicholas G.} and Jarvis, {Christopher I.} and {van Zandvoort}, Kevin and Samuel Clifford and Sun, {Fiona Yueqian} and Sebastian Funk and Graham Medley and Yalda Jafari and Meakin, {Sophie R.} and Rachel Lowe and Matthew Quaife and Waterlow, {Naomi R.} and Eggo, {Rosalind M.} and Jiayao Lei and Mihaly Koltai and Fabienne Krauer and Tully, {Damien C.} and Munday, {James D.} and Alicia Showering and Foss, {Anna M.} and Kiesha Prem and Stefan Flasche and Kucharski, {Adam J.} and Sam Abbott and Quilty, {Billy J.} and Thibaut Jombart and Alicia Rosello and Knight, {Gwenan M.} and Mark Jit and Yang Liu and Jack Williams and Joel Hellewell and Kathleen O{\textquoteright}Reilly and Chan, {Yung Wai Desmond} and Russell, {Timothy W.} and Procter, {Simon R.} and Akira Endo and Nightingale, {Emily S.} and Bosse, {Nikos I.} and Villabona-Arenas, {C. Julian} and Sandmann, {Frank G.} and Amy Gimma and Kaja Abbas and William Waites and Atkins, {Katherine E.} and Barnard, {Rosanna C.} and Petra Klepac and Gibbs, {Hamish P.} and Pearson, {Carl A.B.} and Oliver Brady",

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AU - Jarvis, Christopher I.

AU - van Zandvoort, Kevin

AU - Clifford, Samuel

AU - Sun, Fiona Yueqian

AU - Funk, Sebastian

AU - Medley, Graham

AU - Jafari, Yalda

AU - Meakin, Sophie R.

AU - Lowe, Rachel

AU - Quaife, Matthew

AU - Waterlow, Naomi R.

AU - Eggo, Rosalind M.

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AU - Tully, Damien C.

AU - Munday, James D.

AU - Showering, Alicia

AU - Foss, Anna M.

AU - Prem, Kiesha

AU - Flasche, Stefan

AU - Kucharski, Adam J.

AU - Abbott, Sam

AU - Quilty, Billy J.

AU - Jombart, Thibaut

AU - Rosello, Alicia

AU - Knight, Gwenan M.

AU - Jit, Mark

AU - Liu, Yang

AU - Williams, Jack

AU - Hellewell, Joel

AU - O’Reilly, Kathleen

AU - Chan, Yung Wai Desmond

AU - Russell, Timothy W.

AU - Procter, Simon R.

AU - Endo, Akira

AU - Nightingale, Emily S.

AU - Bosse, Nikos I.

AU - Villabona-Arenas, C. Julian

AU - Sandmann, Frank G.

AU - Gimma, Amy

AU - Abbas, Kaja

AU - Waites, William

AU - Atkins, Katherine E.

AU - Barnard, Rosanna C.

AU - Klepac, Petra

AU - Gibbs, Hamish P.

AU - Pearson, Carl A.B.

AU - Brady, Oliver

PY - 2021/5/13

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N2 - SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.

AB - SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.

KW - SARS CoV-2

KW - PCR tests

KW - mortality

U2 - 10.1038/s41586-021-03426-1

DO - 10.1038/s41586-021-03426-1

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SN - 0028-0836

VL - 593

SP - 270

EP - 274

JO - Nature

JF - Nature

IS - 7858

ER -

Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7

Abstract

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Keywords

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