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

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  1 , Tommy Rampling  2 , Aidan Cross  3 , Heather Bailey  4 , Judith Heaney  5 , Matthew Byott  5 , Rebecca Scott  3 , Rebecca Sconza  6 , Joseph Price  3 , Marios Margaritis  7 , Malin Bergstrom  2 , Moira J Spyer  8 , Patricia B Miralhes  2 , Paul Grant  9 , Stuart Kirk  10 , Chris Valerio  3 , Zaheer Mangera  11 , Thaventhran Prabhahar  3 , Jeronimo Moreno-Cuesta  3 , Nish Arulkumaran  12 , Mervyn Singer  12 , Gee Yen Shin  2 , Emilie Sanchez  2 , Stavroula M Paraskevopoulou  2 , Deenan Pillay  11 , Rachel A McKendry  13 , Mariyam Mirfenderesky  3 , Catherine F Houlihan  14 , Eleni Nastouli  15
Affiliations

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 et al. Lancet Infect Dis. 2021 Sep.

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.

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Conflict of interest statement

Declaration of interests 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.

Figures

Figure 1
Figure 1
Severity of illness across patient age groups and by presence of VOC or non-VOC SARS-CoV-2 infection Figure shows absolute counts (A) and proportion of patients (B). Non-severe disease was defined as reaching a WHO ordinal scale of less than 6 by day 14 after symptom onset. Severe disease was defined as reaching an ordinal scale point of 6 or higher. Death was defined as those who had died by day 28 after the first positive swab. VOC=variant of concern.
Figure 2
Figure 2
Proportion of B.1.1.7 VOC and other lineages observed at UCLH and NMUH, with ONS S gene failure data for London, 2020–21 The period covered by this study is shaded. Genomes were classified as either VOC (B.1.1.7 or VOC-202012/01), non-VOC (all other lineages), or were unclassifiable because of poor sequencing. Data for unclassifiable samples are not shown. All classifications were made using pangolin followed by manual inspection of alignments. ONS=UK Office for National Statistics. NMUH=North Middlesex University Hospital. UCLH=University College London Hospitals. VOC=variant of concern.
Figure 3
Figure 3
A phylogenetic tree of UCLH and NMUH sequenced genomes UCLH samples are coloured blue (123 sequences) and NMUH samples (216 sequences) coloured green. The canonical B.1.1.7 VOC 2012012/01 sequence (GISAID accession EPI_ISL_601443) is highlighted in red. The tree is rooted on a historic SARS-CoV-2 sequence (Wuhan-Hu-1, NC_045512.2) shown in purple, and other representative lineages are shown in black (appendix pp 3–6). The B.1.1.7 VOC lineage is characterised by low within-clade sequence diversity relative to non-VOC strains, displaying a broad expansion of relatively shallow branches. The most frequently observed non-B.1.1.7 lineage in this study, B.1.177, is highlighted for comparison. NMUH=North Middlesex University Hospital. UCLH=University College London Hospitals. VOC=variant of concern.
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