Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study

Dan Frampton; Tommy Rampling; Aidan Cross; Heather Bailey; Judith Heaney; Matthew Byott; Rebecca Scott; Rebecca Sconza; Joseph Price; Marios Margaritis; Malin Bergstrom; Moira J Spyer; Patricia B Miralhes; Paul Grant; Stuart Kirk; Chris Valerio; Zaheer Mangera; Thaventhran Prabhahar; Jeronimo Moreno-Cuesta; Nish Arulkumaran; Mervyn Singer; Gee Yen Shin; Emilie Sanchez; Stavroula M Paraskevopoulou; Deenan Pillay; Rachel A McKendry; Mariyam Mirfenderesky; Catherine F Houlihan; Eleni Nastouli

doi:10.1016/S1473-3099(21)00170-5

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study

Lancet Infect Dis. 2021 Sep;21(9):1246-1256. doi: 10.1016/S1473-3099(21)00170-5. Epub 2021 Apr 12.

Authors

Dan Frampton¹, Tommy Rampling², Aidan Cross³, Heather Bailey⁴, Judith Heaney⁵, Matthew Byott⁵, Rebecca Scott³, Rebecca Sconza⁶, Joseph Price³, Marios Margaritis⁷, Malin Bergstrom², Moira J Spyer⁸, Patricia B Miralhes², Paul Grant⁹, Stuart Kirk¹⁰, Chris Valerio³, Zaheer Mangera¹¹, Thaventhran Prabhahar³, Jeronimo Moreno-Cuesta³, Nish Arulkumaran¹², Mervyn Singer¹², Gee Yen Shin², Emilie Sanchez², Stavroula M Paraskevopoulou², Deenan Pillay¹¹, Rachel A McKendry¹³, Mariyam Mirfenderesky³, Catherine F Houlihan¹⁴, Eleni Nastouli¹⁵

Affiliations

¹ Division of Infection and Immunity, University College London, London, UK; Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK; The Francis Crick Institute, London, UK.
² Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London, UK.
³ North Middlesex University Hospital NHS Trust, London, UK.
⁴ Institute for Global Health, University College London, London, UK.
⁵ Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK; The Francis Crick Institute, London, UK.
⁶ Great Ormond Street Institute of Child Health, University College London, London, UK.
⁷ Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London, UK; London School of Hygiene & Tropical Medicine, London, UK.
⁸ Great Ormond Street Institute of Child Health, University College London, London, UK; Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK; The Francis Crick Institute, London, UK.
⁹ Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK; North Middlesex University Hospital NHS Trust, London, UK.
¹⁰ Health Services Laboratories, London, UK.
¹¹ Division of Infection and Immunity, University College London, London, UK.
¹² Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK.
¹³ London Centre for Nanotechnology, University College London, London, UK; Division of Medicine, University College London, London, UK.
¹⁴ Division of Infection and Immunity, University College London, London, UK; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁵ Great Ormond Street Institute of Child Health, University College London, London, UK; Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK; Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London, UK; The Francis Crick Institute, London, UK. Electronic address: e.nastouli@ucl.ac.uk.

Abstract

Background: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant.

Methods: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths.

Findings: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011).

Interpretation: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort.

Funding: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
COVID-19 / virology*
Cohort Studies
Female
Genome, Viral*
Humans
London
Male
Middle Aged
Phylogeny
SARS-CoV-2 / genetics*
Severity of Illness Index*
United Kingdom
Viral Load
Virus Shedding
Whole Genome Sequencing*