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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]
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“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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“1 in Brazil might threaten measures to control the COVID-19 pandemic due to their ease of transmission (4, 5) and, in case of variants B.”
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COVID-19 Vaccine: Between Myth and Truth
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BackgroundInfluentialSARS-CoV-2 variants lacking ORF8 occurred in farmed mink and pangolin
Pereira, F. (2021) · Gene · doi:10.1016/j.gene.2021.145596 · Cited by 19
Riley, S., Eales, O. D., Walters, C. E., Wang, H., Ainslie, K. E. C., Atchison, C. J., Fronterrè, C., Diggle, P. J., Ashby, D., Donnelly, C. A., et al. (2021) · medRxiv · doi:10.1101/2021.01.28.21250606 · Cited by 17
“The high and rapidly increasing prevalence in the second wave appears partly to be due to the emergence of a more transmissible strain of SARS-CoV-2 that was first observed in southern England in September 2020 [3,4].”
BackgroundResearch progress on vaccine efficacy against SARS-CoV-2 variants of concern
Bian, L., Liu, J., Gao, F., Gao, Q., He, Q., Mao, Q., Wu, X., Xu, M., & Liang, Z. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2057161 · Cited by 30
“7.(45) Further analysis of contact tracing data suggested that infection with Alpha”
BackgroundTemporal spread and evolution of SARS‐CoV‐2 in the second pandemic wave in Brazil
Wolf, J. M., Kipper, D., Borges, G. R., Streck, A. F., & Lunge, V. R. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27371 · Cited by 21
Enright, J. A., Hill, E. M., Stage, H. B., Bolton, K. J., Nixon, E. J., Fairbanks, E. L., Tang, M. L., Brooks‐Pollock, E., Dyson, L., Budd, C. J., et al. (2021) · Royal Society Open Science · doi:10.1098/rsos.210310 · Cited by 18
“…considers regular rounds of testing throughout the academic term and the potential implications of a SARS-CoV-2 variant with increased transmissibility, in light of the emergence of the B.1.1.7 SARS-CoV-2 lineage that proliferated rapidly in the UK in late 2020 and early 2021 [23 – 26] (§3.5).”
BackgroundInfluentialStructural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America
Quinonez, E., Vahed, M., Shahraki, A. H., & Mirsaeidi, M. S. (2021) · Viruses · doi:10.3390/v13050930 · Cited by 16
“7 is more highly transmissible (50 to 70% more) than other SARS-COV-2 variants [12,21].”
BackgroundControlling the pandemic during the SARS-CoV-2 vaccination rollout
Viana, J., van Dorp, C. H., Nunes, A., Gomes, M. C., van Boven, M., Kretzschmar, M., Veldhoen, M., & Rozhnova, G. (2021) · Nature Communications · doi:10.1038/s41467-021-23938-8 · Cited by 136
Managing disease containment measures during a pandemic
Shahmanzari, M., Tanrısever, F., Eryarsoy, E., & Şensoy, A. (2022) · Production and Operations Management · doi:10.1111/poms.13656 · Cited by 15
The race for a COVID-19 vaccine: where are we up to?
Hossain, M. K., Hassanzadeganroudsari, M., Feehan, J., & Apostolopoulos, V. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2021074 · Cited by 17
Pasquale, A. D., Radomski, N., Mangone, I., Calistri, P., Lorusso, A., & Cammà, C. (2021) · BMC Genomics · doi:10.1186/s12864-021-08112-0 · Cited by 23
The role of children and adolescents in the SARS-CoV-2 pandemic: a rapid review
Wiedenmann, M., Goutaki, M., Keiser, O., Stringhini, S., Tanner, M., & Low, N. N. (2021) · Swiss Medical Weekly · doi:10.4414/smw.2021.w30058 · Cited by 15
Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 Isolates
Moustafa, A. M., Bianco, C. M., Denu, L., Ahmed, A., Coffin, S. E., Neide, B., Everett, J. K., Reddy, S. G., Rabut, E., Deseignora, J., et al. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab300 · Cited by 23
Genomic and Epidemiological Analysis of SARS-CoV-2 Viruses in Sri Lanka
Jeewandara, C., Jayathilaka, D., Ranasinghe, D. M. S. H. K., Hsu, S. N., Ariyaratne, D., Jayadas, T. T. P., Madusanka, D., Lindsey, B. B., Gomes, L., Parker, M. D., et al. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.722838 · Cited by 13
Buchan, S., Tibebu, S., Daneman, N., et al. (2021) · medRxiv · doi:10.1101/2021.03.31.21254502 · Cited by 16
Covid-19: Keeping schools as safe as possible
Fontanet, A. L., Grant, R., Greve‐Isdahl, M., & Sridhar, D. (2021) · BMJ · doi:10.1136/bmj.n524 · Cited by 16
Virus Corona (SARS-CoV-2) penyebab COVID-19 kini telah bermutasi
Parwanto, E. (2021) · Jurnal Biomedika dan Kesehatan · doi:10.18051/jbiomedkes.2021.v4.47-49 · Cited by 24
Lee, H., Wang, W., Chauhan, N., Xiong, Y., Magazine, N., Valdescruz, O., Kim, D. Y., Qiu, T., Huang, W., Wang, X., et al. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115228 · Cited by 18
Covid-19 in the UK: policy on children and schools
Gurdasani, D., Pagel, C., McKee, M., Michie, S., Greenhalgh, T., Yates, C. A., Scally, G., & Ziauddeen, H. (2022) · BMJ · doi:10.1136/bmj-2022-071234 · Cited by 14
Bozidis, P., Tsaousi, E., Kostoulas, C., Sakaloglou, P., Gouni, A., Koumpouli, D., Sakkas, H., Georgiou, I. A., & Gartzonika, K. (2022) · Diagnostics · doi:10.3390/diagnostics12040973 · Cited by 15
Snell, L. B., Wang, W., Alcolea-Medina, A., Charalampous, T., Batra, R., de Jongh, L., Higgins, F., Nebbia, G., COG-UK HOCI Investigators, Wang, Y., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-055474 · Cited by 22
Short-term Projections based on Early Omicron Variant Dynamics in EnglandPreprint
Keeling, M. J., Brooks‐Pollock, E., Challen, R., Danon, L., Dyson, L., Gog, J. R., Guzman-Rincon, L. M., Hill, E. M., Pellis, L., Read, J. M., et al. (2021) · medRxiv · doi:10.1101/2021.12.30.21268307 · Cited by 19
Robust clinical detection of SARS‐CoV‐2 variants by RT‐PCR/MALDI‐TOF multitarget approach
Hernandez, M. M., Banu, R., Gonzalez-Reiche, A. S., van de Guchte, A., Khan, Z., Shrestha, P., Cao, L., Chen, F., Shi, H., Hanna, A., et al. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27510 · Cited by 14
From Alpha to Zeta: Identifying Variants and Subtypes of SARS-CoV-2 Via Clustering
Melnyk, A., Mohebbi, F., Knyazev, S., Sahoo, B., Hosseini, R., Skums, P., Zelikovsky, A., & Patterson, M. (2021) · Journal of Computational Biology · doi:10.1089/cmb.2021.0302 · Cited by 21
“One of the first variants of concern (VoCs), the Alpha variant has undergone much investigation, some studies (Volz et al., 2021) showing it to be between 40% and 80% more transmissible.”
InfluentialZamai, L., & Rocchi, M. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15620 · Cited by 14
“In line with this observation, a recent report observed a shift in the age composition, with significantly more UK variant cases among individuals aged 0–19 and significantly fewer UK variant cases among individuals aged 60–79, compared with non-UK variant cases (Volz et al., 2021).”
ResultWidera, M., Mühlemann, B., Corman, V. M., Toptan, T., Beheim-Schwarzbach, J., Kohmer, N., Schneider, J. A., Berger, A., Veith, T., Pallas, C., et al. (2021) · Microorganisms · doi:10.3390/microorganisms9040748 · Cited by 13
Xiao, C., Mao, L., Wang, Z., Gao, L., Zhu, G., Su, J., Chen, X., Yuan, J., Hu, Y., Yin, Z., et al. (2022) · iScience · doi:10.1016/j.isci.2022.103934 · Cited by 21
“7 is spreading substantially faster than preexisting SARS-CoV-2 variants(Davies et al., 2021; Kemp et al., 2020b; Volz et al., 2021).”
BackgroundInfluentialMolecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations
Hendy, M. A., Kaufman, S., & Ponga, M. R. (2021) · Scientific Reports · doi:10.1038/s41598-021-01081-0 · Cited by 17
Lemey, P., Ruktanonchai, N., Hong, S., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-208849/v1 · Cited by 14
Acer, Ö., Bahçe, Y. G., & Özüdoğru, O. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27677 · Cited by 12
“7 lineage, in the second half of 2020 in South East England has been associated with increased rates of transmission and potentially increased disease severity.(8,9) An increase in the number of qPCR‐based community diagnostic tests that fail to detect spike (S) gene amplicons has been linked to an increase in the pre…”
BackgroundSARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants
Khamees, A., Bani-Issa, J., Zoubi, M. S. A., Qasem, T., Alarjah, M. I. A., Alawadin, S. A., Al‐Shami, K., Hussein, F. H., Hussein, E. I., Bashayreh, I. H., et al. (2022) · Pathogens · doi:10.3390/pathogens11020275 · Cited by 19
Brown, K., Gubbay, J., Hopkins, J., et al. (2021) · medRxiv · doi:10.1101/2021.02.09.21251225 · Cited by 13
Modeling the Effect of Population-Wide Vaccination on the Evolution of COVID-19 Epidemic in CanadaPreprint
Berkane, S., Harizi, I., & Tayebi, A. (2021) · medRxiv · doi:10.1101/2021.02.05.21250572 · Cited by 18
“[43] Erik Volz et al.”
BackgroundTang, B., Zhang, X., Li, Q., Bragazzi, N. L., Golemi, D., & Wu, J. (2022) · BMC Public Health · doi:10.1186/s12889-022-13429-w · Cited by 16
Rapid and Flexible RT-qPCR Surveillance Platforms To Detect SARS-CoV-2 Mutations
Spieß, K., Gunalan, V., Marving, E. L., Nielsen, S. H., Jørgensen, M. G. P., Fomsgaard, A. S., Nielsen, L., Alfaro‐Núñez, A., Karst, S. M., Mortensen, S., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.03591-22 · Cited by 24
Ozawa, T., Tani, H., Anraku, Y., Kita, S., Igarashi, E., Saga, Y., Inasaki, N., Kawasuji, H., Yamada, H., Sasaki, S., et al. (2022) · mAbs · doi:10.1080/19420862.2022.2072455 · Cited by 18
Prince, T., Dong, X., Penrice-Randal, R., Randle, N., Hartley, C. S., Goldswain, H., Jones, B., Semple, M. G., Baillie, J. K., Openshaw, P., et al. (2022) · mSphere · doi:10.1128/msphere.00913-21 · Cited by 14
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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