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 - 25/08/21

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

Dan Frampton, PhD ^a,^g,^i,^{*
Joint first authors}, Tommy Rampling, DPhil ^h,^{*
Joint first authors}, Aidan Cross, MBChB ^j,^{*
Joint first authors}, Heather Bailey, PhD ^b,^{*
Joint first authors}, Judith Heaney, PhD ^g,ⁱ, Matthew Byott, MSc ^g,ⁱ, Rebecca Scott, MBChB ^j, Rebecca Sconza, MSc ^c, Joseph Price, MBChB ^j, Marios Margaritis, DPhil ^h,^l, Malin Bergstrom, BMBS ^h, Moira J Spyer, PhD ^c,^g,ⁱ, Patricia B Miralhes, MBBS ^h, Paul Grant, PhD ^g,^j, Stuart Kirk, Msc ^k, Chris Valerio, MBChB ^j, Zaheer Mangera, MA ^a, Thaventhran Prabhahar, FFICM ^j, Jeronimo Moreno-Cuesta, MD ^j, Nish Arulkumaran, PhD ^d, Mervyn Singer, ProfFRCP ^d, Gee Yen Shin, FRCPath ^h, Emilie Sanchez, MD ^h, Stavroula M Paraskevopoulou, MBBS ^h, Deenan Pillay, ProfPhD ^a, Rachel A McKendry, ProfPhD ^e,^f, Mariyam Mirfenderesky, FRCPath ^j, Catherine F Houlihan, PhD ^a,^h,^{^{†
Authors contributed equally}}, Eleni Nastouli, FRCPath ^c,^g,^h,^i,⁎, ^{^{†
Authors contributed equally}}
^a Division of Infection and Immunity, University College London, London, UK
^b Institute for Global Health, University College London, London, UK
^c Great Ormond Street Institute of Child Health, University College London, London, UK
^d Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK
^e London Centre for Nanotechnology, University College London, London, UK
^f Division of Medicine, University College London, London, UK
^g Advanced Pathogen Diagnostics Unit, University College London Hospitals NHS Foundation Trust, London, UK
^h Department of Clinical Virology, University College London Hospitals NHS Foundation Trust, London, UK
ⁱ The Francis Crick Institute, London, UK
^j North Middlesex University Hospital NHS Trust, London, UK
^k Health Services Laboratories, London, UK
^l London School of Hygiene & Tropical Medicine, London, UK

^*Correspondence to: Dr Eleni Nastouli, Great Ormond Street Institute of Child Health, University College London, London, UKGreat Ormond Street Institute of Child HealthUniversity College LondonLondonUK

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Summary

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.

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Plan

Introduction

Methods

Study design and setting

Viral detection for SARS-CoV-2

Next-generation sequencing (NGS) and genomic data analysis

Association with clinical severity

Statistical analysis

Role of the funding source

Results

Discussion

Data sharing

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Vol 21 - N° 9

P. 1246-1256 - septembre 2021 Retour au numéro

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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 - 25/08/21

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