Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data
Open accessPreprint — published as 10.1038/s41586-021-03470-x · Paper page
Abstract
The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.
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Mild restrictions that kept the parametric reproduction number around 0.9 with the original virus strain would keep it around 1.3 (at least) if new variants increase transmissibility by at least 40-50%.
“In particular, the mild restrictions that kept around 0.9 with the original virus strain would keep it around 1.3 (at least) if the new variants increase transmissibility of at least 40–50%, as reported in the literature49–51.”
From Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy (2021) · cites this paper as [49]
In 'Estimating reproduction numbers for VOC and non-VOC independently' (page unavailable), the paper reports mean reproduction numbers of 0.92 for non-VOC strains and 1.45 for B.1.1.7 during England’s second lockdown. The Abstract (page unavailable) estimates a 1.4–1.8 ratio, supporting the approximate numerical comparison. But the paper describes high levels of social distancing, not mild restrictions, and cautions against extrapolating its estimate to other transmission contexts or variants. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRecently, viral variants of concern have emerged in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility.
“Recently, viral variants of concern have emerged in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility (50–55).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [51]
SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2).
“SARS-CoV-2 and SARS-CoV enter host cells through binding of the S glycoprotein to angiotensin converting enzyme 2 (ACE2)1,28.”
From Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies (2021) · cites this paper as [1]
The N501Y mutation has been reported to increase transmissibility of the B.1.17 variant circulating in the UK.
“and has been reported to increase transmissibility of the B.1.17 variant circulating in the UK.16”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [16]
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“7 variant increased relative to other variants during a lockdown period, which should have limited opportunities for transmission [16].”
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BackgroundMethodRecurrent emergence and transmission of a SARS-CoV-2 spike deletion H69/V70
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“𝑅𝑅𝑅𝑅 We note that other work has shown that the degree of transmission advantage exhibited by the B.1.1.7 can vary over time as a function of control interventions and behavior ( 68 ).”
InfluentialSelf-citationMultiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2
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“…estimated that B.1.1.7 is approximately 50% more transmissible (Davies et al., 2020), which could increase the average number of people that one infected person will pass the virus to (effective reproductive rate) by between 0.4 and 0.7 people (Volz et al., 2021).”
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“The transmission rate was 40–70% more than the original virus [15].”
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“The emergence of several SARS-CoV-2 variants of concern (VOC) with multiple amino acid replacements has implications for the future control of the COVID-19 pandemic (Davies et al., 2020; Kirby, 2021; Tegally et al., 2020; Volz et al., 2021).”
An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants
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Just 2% of SARS-CoV-2−positive individuals carry 90% of the virus circulating in communities
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“”) SARS-CoV-2 variant, and subsequent major variants of concern, were first documented in the United States during the final weeks of 2020 and the beginning of 2021 [21].”
BackgroundEvaluation of COVID-19 vaccination strategies with a delayed second dose
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“Challenges with vaccine supply and rollout, coupled with a deadly wave of outbreaks that overwhelmed hospitals [48–50], and the emergence of highly transmissible SARS-CoV-2 variants [12,51,52], sparked a debate as to whether available vaccines should be used to rapidly increase the coverage with the first dose [14–17]…”
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“Of the patients who were not receiving invasive mechanical ventilation at baseline, the number of patients progressing to the prespecified composite secondary outcome of invasive mechanical ventilation or death was similar in the two groups (1568 [29”
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“Therefore, SARS-CoV-2 variants can emerge and increase greatly in number over time in the absence of any clear or sustained selective advantage.”
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Self-citationThe emerging SARS-CoV-2 variants of concern
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“harbor specific mutations in their S proteins that may be associated with increased transmissibility (Davies et al., 2020; Faria et al., 2021; Rambaut et al., 2020; Sabino et al., 2021; Tegally et al., 2020; Volz et al., 2021).”
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“7 lineage, first identified in the United Kingdom (UK), includes the N501Y mutation which has been associated with 53% increased transmissibly.(18) Neutralizing antibody activity elicited by infection or mRNA vaccines against the B.”
BackgroundEarly introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States
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“For a more transmissible strain (such as the recently iden-tified UK variant [46,47]) with an R 0 of 4 the coverage required for herd immunity increases to 75%.”
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Accelerated vaccine rollout is imperative to mitigate highly transmissible COVID-19 variants
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“These new variants exhibit a multiplicative transmissibility up to 74% higher than the original strain, [5 (cid:1) 7] and higher case fatality rates [8,9].”
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“7) variant, which was first detected in the United Kingdom, demonstrated enhanced transmissibility [51,52], a longer duration of acute infection [53], a higher hospitalization rate [54], and probably a higher infection fatality rate than previously circulating variants [51,55-57].”
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“Some harbor specific mutations in S that are associated with increased transmissibility and/or immune evasion (Davies et al., 2021; Sabino et al., 2021; Tegally et al., 2020; Volz et al., 2021).”
Emergence and expansion of SARS-CoV-2 B.1.526 after identification in New York
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The European Health Data Space
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“7 variant had a positive growth rate [7, 8].”
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“Others VOCs have been isolated in South Africa and Brazil and have been studied for their enhanced contagiousness and resistance to neutralization by antibodies from convalescent and vaccine-recipient subjects (6-8) (Table 1).”
BackgroundDroplet digital RT-PCR to detect SARS-CoV-2 signature mutations of variants of concern in wastewater
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An action plan for pan-European defence against new SARS-CoV-2 variants
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“1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility (50-55).”
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SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants
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“Worst of all, as the COVID-19 pandemic rages on, there have emerged variants of SARS-CoV-2 in the different regions of the world, including the United Kingdom (UK), South Africa (SA), Brazil, and the United States[1-3].”
BackgroundSARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?
Chakraborty, S., Mallajosyula, V. V. A., Tato, C. M., Tan, G. S., & Wang, T. T. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.01.014 · Cited by 87 · see citing works
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The emergence of new strains of SARS-CoV-2. What does it mean for COVID-19 vaccines?
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“92 for the original non-mutated SARS-CoV-2 virus [11].”
BackgroundWere pregnant women more affected by COVID-19 in the second wave of the pandemic?
Kadiwar, S., Smith, J. J., Ledot, S., Johnson, M., Bianchi, P. A., Singh, N., Montanaro, C., Gatzoulis, M., Shah, N. M., & Ukor, E.-F. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00716-9 · Cited by 92 · see citing works
Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2
Fischhoff, I. R., Castellanos, A. A., Rodrigues, J., Varsani, A., & Han, B. A. (2021) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2021.1651 · Cited by 85 · see citing works
“…the transmission chain (Garry, 2021; Oude Munnink et al., 2020) affects host range (Rodrigues et al., 2020) or leads to distinct epidemiology in humans (e.g., via increased transmissibility among humans (Davies et al., 2020; Volz et al., 2021), but see (Rambaut et al., 2020; Tegally et al., 2020)).”
- Authors
- Volz, E., Mishra, S., Chand, M., Barrett, J. C., Johnson, R., Geidelberg, L., Hinsley, W. R., Laydon, D. J., Dabrera, G., O’Toole, Á., Amato, R., Ragonnet-Cronin, M., Harrison, I., Jackson, B., Ariani, C. V., Boyd, O., Loman, N. J., McCrone, J. T., Gonçalves, S., Jorgensen, D., Myers, R., Hill, V., Jackson, D. K., Gaythorpe, K., Groves, N., Sillitoe, J., Kwiatkowski, D. P., The COVID-19 Genomics UK (COG-UK) consortium, Flaxman, S., Ratmann, O., Bhatt, S., Hopkins, S., Gandy, A., Rambaut, A., & Ferguson, N. M.
- Affiliations
- Imperial College London (GB)
- Public Health England (GB)
- Wellcome Sanger Institute (GB)
- University of Edinburgh (GB)
- University of Copenhagen (DK)
- Corresponding author
- Volz, Erik
- Ferguson, Neil M
- ORCID
- Volz, Erik
- Mishra, Swapnil
- Chand, Meera
- Barrett, Jeffrey C.
- Geidelberg, Lily
- Hinsley, Wes R
- Laydon, Daniel J
- Dabrera, Gavin
- Harrison, Ian
- Jackson, Ben
- Ariani, Cristina V.
- Boyd, Olivia
- Loman, Nicholas J
- McCrone, John T
- Gonçalves, Sónia
- Jorgensen, David
- Myers, Richard
- Hill, Verity
- Jackson, David K.
- Gaythorpe, Katy
- Groves, Natalie
- Kwiatkowski, Dominic P.
- Flaxman, Seth
- Ratmann, Oliver
- Bhatt, Samir
- Hopkins, Susan
- Gandy, Axel
- Rambaut, Andrew
- Ferguson, Neil M
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-01-04
- Volume
- 593
- Issue
- 7858
- Pages
- 266-269
- ISSN
- 0028-0836 (ISSN-L)
- OpenAlex
- W3136588845
- Cited by
- 1,611
- References
- 28
- Citations by year
- 2026: 38 · 2025: 86 · 2024: 116 · 2023: 216 · 2022: 464 · 2021: 685 · 2020: 5 · 2012: 1
- FWCI
- 116.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Northumbria Research Link (Northumbria University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Bill and Melinda Gates Foundation (OPP 1175094, 206194, OPP1197730, MR/R015600/1, OPP1084362)
- Wellcome Trust (MR/R015600/1, 204911/Z/16/Z, Z/17/Z, 206298/Z/17/Z, RDA02, 206298, 206194)
- UK Research and Innovation (MR/V038109/1, MR/R015600/1, MC_PC_19027)
- National Institute for Health Research Health Protection Research Unit
- Cancer Research UK (23923)
- National Institute for Health and Care Research (PR-OD-1017–20002, MR/R015600/1, RDA02, NIHR301445, OPP1175094, ACF-2018-04-014)
- Academy of Medical Sciences (AMS-CSF4-Torok, SBF004\1080)
- Imperial College London (MR/R015600/1)
- European Commission (725422, MR/R015600/1, 101003653, COVID-19, 206298/Z/17/Z)
- Rural Development Administration
- Novo Nordisk (NNF20OC0059309)
- Novo Nordisk Fonden (NNF20OC0059309)
- Medical Research Council (MR/R015600/1, MR/M006212/1, MC_PC_19026, MR/V038109/1, MR/S00291X/1, MC_PC_19012, COVID-19)
- Engineering and Physical Sciences Research Council (EP/V002910/1, EP/V002910/2)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, B.1.1.7 lineage, variants of concern, transmissibility, S-gene target failure, time-varying reproduction number, viral genomic surveillance, COVID-19 pandemic, England
- MeSH terms
- COVID-19, SARS-CoV-2, Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, England, Humans, Infant, Infant, Newborn, Middle Aged, Phylogeny, Time Factors, Genome, Viral, Age Distribution, Evolution, Molecular, Basic Reproduction Number, Young Adult, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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