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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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“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
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“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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Genomic surveillance at scale is required to detect newly emerging strains at an early timepointPreprint
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“17 variant circulating in the UK.(15) The E484K mutation has been”
BackgroundInfluentialFrom Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines
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ResultPCR assay to enhance global surveillance for SARS-CoV-2 variants of concernPreprint
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“5 times more transmissible than the original wild type strain (Rees-Spear et al., 2021; Horby et al., 2021; Volz et al., 2021; Grabowski et al., 2021; Davies et al., 2021).”
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“The vast majority of sequenced SARS-CoV-2 isolates contain a D614G mutation in the spike protein [3] that increases viral infectivity and transmissibility [4-6] and subsequently, variants with multiple mutations in the spike protein and enhanced transmissibility have emerged in the United Kingdom [7-9], South Africa […”
BackgroundCOVID-19, the first pandemic in the post-genomic era
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Coincident rapid expansion of two SARS-CoV-2 lineages with enhanced infectivity in Nigeria
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“The average age of the patients was 42 years (range [11-84]) and the gender distribution was 50% female and 50% male.”
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“7 lineage variants are highly contagious (27, 28) and have become dominant throughout the US (23).”
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Nagy‐Szakal, D., Couto-Rodriguez, M., Wells, H., Barrows, J., Debieu, M., Butcher, K. D., Chen, S., Berki, A., Hager, C., Boorstein, R. J., et al. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.00197-21 · Cited by 36
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Beyond Six Feet: A Guideline to Limit Indoor Airborne Transmission of COVID-19Preprint
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Estimating the strength of selection for new SARS-CoV-2 variants
van Dorp, C. H., Goldberg, E. E., Hengartner, N., Ke, R., & Romero-Severson, E. O. (2021) · Nature Communications · doi:10.1038/s41467-021-27369-3 · Cited by 30
“Molecular epidemiology is a powerful framework comprised of a broad collection of methods and software designed to facilitate the analysis of pathogen genetic sequence data [1, 2, 3, 9].”
InfluentialThe Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City
Cedro‐Tanda, A., Gómez-Romero, L., Alcaraz, N., de Anda‐Jáuregui, G., Peñaloza, F., Moreno, B., Escobar-Arrazola, M. A., Ramirez-Vega, O. A., Munguía-Garza, P., Garcia-Cardenas, F., et al. (2021) · Viruses · doi:10.3390/v13112182 · Cited by 32
Brejová, B., Boršová, K., Hodorová, V., Čabanová, V., Reizigová, L., Paul, E. D., Čekan, P., Klempa, B., Nosek, J., & Vinař, T. (2021) · Virus Genes · doi:10.1007/s11262-021-01866-5 · Cited by 47
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matOptimize: a parallel tree optimization method enables online phylogenetics for SARS-CoV-2
Ye, C., Thornlow, B. P., Hinrichs, A. S., Krämer, A., Mirchandani, C., Torvi, D., Lanfear, R., Corbett-Detig, R. B., & Turakhia, Y. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac401 · Cited by 36
“Phylogenetic trees have also helped in establishing transmission links between infections (5), in disambiguating community transmission from outside introductions (6, 7), in identifying the mutations that might have conferred increased transmissibility to the virus (8, 9), and for estimating the reproduction number (R…”
Butera, Y., Mukantwari, E., Artesi, M., Umuringa, J. D., O’Toole, Á., Hill, V., Rooke, S., Hong, S. L., Dellicour, S., Majyambere, O., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25985-7 · Cited by 36
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“The speed with which the disease can spread, even amid reduced travel, was recently re-illustrated by the spread of the newly emerged B.1.1.7 variant from the UK [ 18 , 19 ].”
InfluentialProjecting the impact of a two-dose COVID-19 vaccination campaign in Ontario, Canada
VILCHES, T. N., Zhang, K., Exan, R. V., Langley, J. M., & Moghadas, S. M. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.03.058 · Cited by 39
Weiss, A., Touret, F., Baronti, C., Gilles, M., Hoen, B., Nougaırède, A., de Lamballerie, X. N., & Sommer, M. O. A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260958 · Cited by 45
SARS-CoV-2 Variants, RBD Mutations, Binding Affinity, and Antibody Escape
Yang, L., Li, J., Guo, S., Hou, C., Liao, C., Shi, L., Ma, X., Jiang, S., Zheng, B., Fang, Y., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212114 · Cited by 35
Dispersal dynamics of SARS-CoV-2 lineages during the first epidemic wave in New York City
Dellicour, S., Hong, S. L., Vrancken, B., Chaillon, A., Gill, M. S., Maurano, M. T., Ramaswami, S., Zappile, P., Marier, C., Harkins, G. W., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009571 · Cited by 38
“V1 are associated with a higher transmissibility [15,16], monitoring their colonization should be a top priority in the upcoming months.”
BackgroundThe localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York StatePreprint
Lasek‐Nesselquist, E., Lapierre, P., Schneider, E., George, K. S., & Pata, J. D. (2021) · medRxiv · doi:10.1101/2021.02.26.21251868 · Cited by 38
Emergence of an early SARS-CoV-2 epidemic in the United StatesPreprint
Zeller, M., Gangavarapu, K., Anderson, C., Smither, A. R., Vanchiere, J. A., Rose, R., Snyder, D. J., Dudas, G., Watts, A., Matteson, N. L., et al. (2021) · medRxiv · doi:10.1101/2021.02.05.21251235 · Cited by 8
Murray, M. J., McIntosh, M., Atkinson, C. E., Mahungu, T. W., Wright, E., Chatterton, W., Gandy, M., & Reeves, M. B. (2021) · Journal of Infection · doi:10.1016/j.jinf.2021.03.010 · Cited by 28
Sachs, J. D., Abdool Karim, S., Aknin, L., Allen, J., Brosbøl, K., Cuevas Barron, G., Daszak, P., Fernanda Espinosa, M., Gaspar, V., Gaviria, A., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00388-3 · Cited by 30
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“We assumed that transmission from 1 December 2020 onwards would persist at the mean level observed in September - November 2020 (the “medium transmission” scenario).”
BackgroundInfluentialWeber, S., Ramirez, C. M., Weiser, B., Burger, H., & Doerfler, W. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114062 · Cited by 26
Fidan, Ö., Mujwar, S., & Kciuk, M. (2022) · Molecular Diversity · doi:10.1007/s11030-022-10440-6 · Cited by 42
“This mutation resulted in a high transmission (40–70% increased transmissibility) in the context of high population immunity, which promoted the emergence and spread of the variants [5, 6].”
BackgroundWu, J., Scarabel, F., McCarthy, Z., Xiao, Y., & Ogden, N. H. (2021) · Canada Communicable Disease Report · doi:10.14745/ccdr.v47i78a06 · Cited by 28
Dicken, S. J., Murray, M. J., Thorne, L., Reuschl, A., Forrest, C., Ganeshalingham, M., Muir, L., Kalemera, M. D., Palor, M., McCoy, L. E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.22.436468 · Cited by 30
ACE2‐based decoy receptors for SARS coronavirus 2
Jing, W., & Procko, E. (2021) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26140 · Cited by 32
Evolving biothreat of variant SARS-CoV-2 - molecular properties, virulence and epidemiology.
Kannan, S., Ali, P., & Sheeza, A. (2021) · European Review for Medical and Pharmacological Sciences · doi:10.26355/eurrev_202106_26151 · Cited by 29
Evaluation of different types of face masks to limit the spread of SARS-CoV-2: a modeling study
Gurbaxani, B. M., Hill, A. N., Paul, P., Prasad, P. V., & Slayton, R. B. (2022) · Scientific Reports · doi:10.1038/s41598-022-11934-x · Cited by 29
Surveillance of SARS-CoV-2 lineage B.1.1.7 in Slovakia using a novel, multiplexed RT-qPCR assay
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“The transmission advantage has been confirmed by epidemiological data in the UK 15,16 .”
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Communicate hope to motivate the public during the COVID-19 pandemic
Petersen, M. B., Christiansen, L. E., Bor, A., Lindholt, M. F., Jørgensen, F. J., Adler‐Nissen, R., Roepstorff, A., & Lehmann, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-06316-2 · Cited by 41
“Because of higher infectiousness, the Alpha variant increased the risk of large outbreaks 25 , intensifying the need for citizens to engage in protective behavior 9 , at a time where populations across the globe were strained with pandemic fatigue 10,18 .”
BackgroundEfficacy of FFP3 respirators for prevention of SARS-CoV-2 infection in healthcare workers
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Metadata
- 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
- 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
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