Article Text

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study
  1. Oliver Stirrup1,
  2. Florencia Boshier2,
  3. Cristina Venturini2,
  4. José Afonso Guerra-Assunção2,3,
  5. Adela Alcolea-Medina4,5,
  6. Angela Beckett6,7,
  7. Themoula Charalampous4,
  8. Ana da Silva Filipe8,
  9. Sharon Glaysher9,
  10. Tabassum Khan10,
  11. Raghavendran Kulasegaran Shylini10,
  12. Beatrix Kele10,
  13. Irene Monahan11,
  14. Guy Mollett8,
  15. Matthew Parker12,13,14,
  16. Emanuela Pelosi15,
  17. Paul Randell16,
  18. Sunando Roy2,
  19. Joshua Taylor17,
  20. Sophie Weller18,
  21. Eleri Wilson-Davies15,
  22. Phillip Wade19,20,
  23. Rachel Williams3,
  24. The COG-UK-HOCI Variant substudy consortium,
  25. The COVID-19 Genomics UK (COG-UK) consortium,
  26. Andrew Copas1,
  27. Maria-Teresa Cutino-Moguel10,
  28. Nick Freemantle21,
  29. Andrew C Hayward22,
  30. Alison Holmes23,24,
  31. Joseph Hughes8,
  32. Tabitha Mahungu18,
  33. Gaia Nebbia4,25,
  34. David Partridge19,20,
  35. Cassie Pope11,26,
  36. James Price27,
  37. Samuel Robson6,28,
  38. Kordo Saeed29,30,
  39. Thushan de Silva19,20,
  40. Luke Snell4,25,
  41. Emma Thomson8,
  42. Adam A Witney11 and
  43. Judith Breuer2,31
    1. 1Institute for Global Health, University College London, London, UK
    2. 2Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
    3. 3Department of Genetics & Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
    4. 4Centre for Clinical Infection and Diagnostics Research, School of Immunology and Microbial Sciences, King’s College London, London, UK
    5. 5Infection Sciences, Viapath, London, UK
    6. 6Centre for Enzyme Innovation, University of Portsmouth, Portsmouth, UK
    7. 7School of Biological Sciences, University of Portsmouth, Portsmouth, UK
    8. 8MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
    9. 9Portsmouth Hospitals University NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
    10. 10Division of Infection, The Royal London Hospital, Barts Health NHS Trust, London, UK
    11. 11Institute for Infection and Immunity, St George’s University of London, London, UK
    12. 12Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, UK
    13. 13Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, UK
    14. 14Sheffield Biomedical Research Centre, The University of Sheffield, Sheffield, UK
    15. 15Southampton Specialist Virology Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
    16. 16Department of Infection and Immunity, North West London Pathology, London, UK
    17. 17Department of Microbiology, South West London Pathology, St. George’s Hospital, London, UK
    18. 18Department of Virology, Royal Free London NHS Foundation Trust, London, UK
    19. 19Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
    20. 20The Florey Institute for Host-Pathogen Interactions & Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK
    21. 21Institute of Clinical Trials and Methodology, University College London, London, UK
    22. 22Institute of Epidemiology and Health Care, University College London, London, UK
    23. 23Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK
    24. 24Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
    25. 25Department of Infectious Diseases, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK
    26. 26Infection Care Group, St George’s University Hospitals NHS Foundation Trust, London, UK
    27. 27Imperial College Healthcare NHS Trust, London, UK
    28. 28School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
    29. 29Microbiology Innovation and Research Unit (MIRU), Department of Microbiology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
    30. 30Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, UK
    31. 31Department of Microbiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
    1. Correspondence to Dr Oliver Stirrup; oliver.stirrup{at}ucl.ac.uk

    Abstract

    Background SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented.

    Methods We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity.

    Findings Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086).

    Interpretation In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.

    • COVID-19
    • viral infection

    Data availability statement

    The sequence data analysed are included within publicly available datasets (https://www.cogconsortium.uk/data/). However, due to data governance restrictions it is not possible to share the associated patient characteristics and clinical outcome data for the analysis described, as these are considered sensitive and full anonymisation is not possible. The corresponding author (OTS) affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted and that any discrepancies from the study as planned have been explained.

    https://creativecommons.org/licenses/by/4.0/

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    Data availability statement

    The sequence data analysed are included within publicly available datasets (https://www.cogconsortium.uk/data/). However, due to data governance restrictions it is not possible to share the associated patient characteristics and clinical outcome data for the analysis described, as these are considered sensitive and full anonymisation is not possible. The corresponding author (OTS) affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted and that any discrepancies from the study as planned have been explained.

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    Footnotes

    • OS, FB, CV and JAG-A contributed equally.

    • Collaborators Composition of the COG-UK HOCI Variant substudy consortium members (excluding those on main authorship): study oversight and quality assurance UCL Comprehensive Clinical Trials Unit: James Blackstone, Leanne Hockey, Georgia Marley. Collection of samples, sequence data and meta-data: Barts Health Trust, David Harrington, Anna Riddell; Queen Elizabeth University Hospital, NHS Greater Glasgow & Clyde (QEUH), Christine Peters; Guy’s and St Thomas’ NHS Foundation Trust and Centre for Clinical Infection & Diagnostics Research, King’s College London, Flavia Flaviani, Bindi Patel, Tom G S Williams, Rahul Batra, Jonathan D Edgeworth; North West London Pathology, Pinglawathee Madona, Alison Cox; Royal Free London NHS Foundation Trust, Jennifer Hart, Tanzina Haque, Dianne Irish; UCL Pathogen Genomics Unit, Juanita Pang, Charlotte Williams, Helena Tutill, Nadua Bayzid, Marius Cotic; University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Luke Green, Benjamin Lindsey, Amy State, Alison Cope, Katie Johnson, Adrienn Angyal, Peijun Zhang, Max Whiteley, Marta Gallis Ramalho, Stella Christou, Stavroula Louka, Hailey Hornsby, Benjamin Foulkes, Paige Wolverson, Joe Heffer, Nikki Smith; University of Portsmouth, Salman Goudarzi, Chris Fearn, Kate Cook, Katie Loveson; Portsmouth Hospitals University NHS Trust, Scott Elliott; University Hospital Southampton NHS Foundation Trust, Adhyana Mahamana, Buddhini Samaraweera, Siona Silveira, Stephen Aplin, Sarah Jeremiah, Helen Umpleby, Helen Wheeler, Matthew Harvey, Thea Sass, Jacqui Prieto; St Georges University and Healthcare Trust, Kenneth Laing, Ngee Keong Tan, Claudia Cardoso Pereira; University College London Hospitals NHS Foundation Trust UCLH Advanced Pathogen Diagnostics Unit, Eleni Nastouli, Catherine F Houlihan, Dan Frampton, Tommy Rampling, Matt Byott, Judith Heaney, Gee Yen Shin, Moira Spyer, Malin Bergstrom, Emilie Sanchez, Stavroula M Paraskevopoulou, Marios Margaritis.

    • Contributors OS, FB, CV, JAG-A, ACJ, NF, ACH and JB planned the analysis and drafted the first draft of the manuscript. AA-M, AB, TC, AdSF, SG, TK, RKS, BK, IM, GM, MP, EP, PR, SR, JT, SW, EW-D, PW, RW, M-TC-M, AH, JH, TM, GN, DP, CP, JP, SR, KS, TdS, LS, ET, AAW extracted and provided sequencing data and patient characteristics and outcome data. OS, FB, CV and JAG-A had full access to and verified the final collated dataset. FB, CV and JAG-A carried out phylogenetic lineage assignments and merged the final dataset for analysis, and OTS carried out statistical modelling. All authors reviewed the final manuscript and approved this for submission. OTS is the guarantor of the study. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

    • Funding This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute.

    • Disclaimer The funder of the study had no role in the study design, the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the paper for publication.

    • Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: OTS has received funding for the submitted work through the COG-UK-HOCI study, funded by COG-UK consortium, supported by funding from UK Research & Innovation, National Institute of Health Research and Wellcome Sanger Institute; the COG-UK consortium funded sequencing costs for the submitted work; NF reports grants from UKRI, during the conduct of the study; personal fees from Aimmune, personal fees from ALK, personal fees from AstraZeneca, personal fees from MSD, personal fees from Sanofi Aventis, personal fees from Novartis, personal fees from Ipsen, personal fees from Gedeon Richter, personal fees from Galderma, personal fees from Vertex, outside the submitted work. The remaining authors do not have any declarations of interest. All other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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