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 ArulkumaranMervyn Singer, Gee Yen Shin, Emilie Sanchez, Stavroula M. Paraskevopoulou, Deenan Pillay, Rachel A. McKendry, Mariyam Mirfenderesky, Catherine F. Houlihan, Eleni Nastouli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1246-1256
Number of pages11
JournalThe Lancet Infectious Diseases
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 2021
Externally publishedYes

Bibliographical note

Funding Information:
UCLH Advanced Pathogens Diagnostic Unit receives funding from the University College London Hospitals NHS Trust. The APDU Illumina sequencing platform was funded by a grant from the UCLH/UCL UK National Institute for Health Research Biomedical Research Centre in 2017. APDU participates in COG-UK as a sequencing site but receives no funding from COG-UK. APDU whole-genome sequencing data are uploaded in real time on the COG-UK servers. DF was funded by the i-sense Engineering and Physical Sciences Research Council Interdisciplinary Research Collaborations in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (EP/R00529X/1). EN, MJS, and JH receive funding from the EU Horizon 2020 programme (734857 and 862840). We thank Nathan Lea, information governance officer at UCLH, and Maurice Griffin at the UCLH/UCL Joint Research Office for their help with ethics applications; Lisa Levett, at Health Services Laboratories, and Jerome Nicod, at Francis Crick Institute, for their support for APDU; and Mike Brown, Kirit Ardeshna, and Alun Marc Henry, all UCLH and NMUH clinicians, including Sarjana Jain and Teh Li Chin, for their critical reading of the manuscript.

Funding Information:
MS reports funding support for at-cost development and manufacture of UCL-Ventura continuous positive airway pressure device for patients with COVID-19 from the UK Department of Health and Social Care, during the conduct of the study; grants and advisory board fees paid to institution research fund from NewB; grants from DSTL; advisory board and speaking fees paid into institutional research fund from Amormed, Biotest, General ElectricBaxter, Baxter, Roche, Bayer, and Shionogi; and grants from Critical Pressure and Apollo Therapeutics, outside the submitted work. All other authors declare no competing interests.

Funding Information:
The clinical information and SARS-CoV-2 PCR samples were collected as part of routine clinical care. Data were extracted and analysed using permission granted by the National Health Service London Westminster Research Ethics Committee (IRAS 284088; REC 20/HRA/2505).

Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

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