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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]
In the citing paper
“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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The new UK SARS-CoV-2 variant and lockdown – causes and consequences
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Evaluation of COVID-19 vaccination strategies with a delayed second dose
Moghadas, S. M., VILCHES, T. N., Zhang, K., Nourbakhsh, S., Sah, P., Fitzpatrick, M. C., & Galvani, A. P. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001211 · Cited by 154
“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]…”
Snell, L., Wang, W., Alcolea-Medina, A., et al. (2021) · medRxiv · doi:10.1101/2021.03.16.21253377 · Cited by 8
“transmissibility in community studies [11] [12] [13], and there is evidence from community studies that it may 85 also confer increased mortality [14] [15] [16] [17].”
BackgroundClark, J. J., Sharma, P., Bentley, E. G., Harding, A. C., Kipar, A., Neary, M., Box, H., Hughes, G. L., Patterson, E. I., Sharp, J., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.10.434447 · Cited by 7
Progressing adaptation of SARS-CoV-2 to humans
Konishi, T. (2020) · bioRxiv · doi:10.1101/2020.12.18.413344 · Cited by 8
Dings, C., Götz, K. M., Och, K., Sihinevich, I., Werthner, Q., Smola, S., Bliem, M., Mahfoud, F., Volk, T. J., Kreuer, S., et al. (2022) · Viruses · doi:10.3390/v14102114 · Cited by 10
Jessop, Z. M., Gibson, J. A. G., Lim, J. Y., Jovic, T. H., Combellack, E. J., Dobbs, T. D., Carter, K., Hiles, S., Islam, S., Healy, B., et al. (2022) · Trials · doi:10.1186/s13063-022-06685-z · Cited by 9
Panzera, Y., Ramos, N., Calleros, L., Marandino, A. E., Tomás, G., Techera, C., Grecco, S., Frabasile, S., Fuques, E., Cóppola, L., et al. (2021) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/0074-02760210275 · Cited by 7
“(8) In addition, identifying mutations is acquiring more relevance with the emergence of genetic variants of concern that potentially impact virus control and vaccine development.(9,10,11) The most common changes in SARS-CoV-2 are single nucleotide polymorphisms (SNPs),(12,13) but indels are also detected at high freq…”
BackgroundLacy, J., Mensah, A., Simmons, R., et al. (2022) · Epidemiology and Infection · doi:10.1101/2022.01.10.22268896 · Cited by 7
“The emergence of the alpha [13], beta [14], gamma [15], delta [16] and most recently omicron [17] SARS-CoV-2 variants was a cause for concern, not only for the apparent increased transmissibility of subsequent variants [13, 18], associated with mutations in the spike protein [19, 20] but also for the increased risk of…”
BackgroundEffective mathematical modelling of health passes during a pandemic
Hohenegger, S., Cacciapaglia, G., & Francesco Sannino, A. (2022) · Scientific Reports · doi:10.1038/s41598-022-10663-5 · Cited by 8
Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa
Okoh, O. S., Nii-Trebi, N., Jakkari, A., et al. (2021) · medRxiv · doi:10.1101/2021.05.17.21257341 · Cited by 7
“Almost simultaneously, the independent emergence of the VOC 20C/501Y.V2 belonging to Pango lineage B.1.351, or Beta VOC was detected in South Africa (Tegally et al., 2021).”
InfluentialBarton, M. I., MacGowan, S., Kutuzov, M. A., Dushek, O., Barton, G., & van der Merwe, P. A. (2021) · bioRxiv · doi:10.1101/2021.05.18.444646 · Cited by 9
“(Volz et al., 2021a, 2021b) The SARS-CoV-2 virus enters cells following an interaction between the Spike (S) protein on its surface with angiotensin-converting enzyme 2 (ACE2) on cell surfaces (V’kovski et al., 2021).”
BackgroundInfluentialGuerrero-Preston, R. E., Rivera‐Amill, V., Caraballo, K., Rodríguez‐Torres, S., Purcell‐Wiltz, A., García, A. A., Torres, R. S., Zamunér, F. T., Zanettini, C., MacKay, M. J., et al. (2022) · Immunity Inflammation and Disease · doi:10.1002/iid3.634 · Cited by 8
“7, was detected in the United Kingdom in November 2020 and has now spread to multiple countries worldwide [6-8].”
BackgroundComputation of COVID-19 epidemiological data in Hungary using dynamic model inversion
Csutak, B., Polcz, P., & Szederkényi, G. (2021) · IEEE International Symposium on Applied Computational Intelligence and Informatics (SACI) · doi:10.1109/saci51354.2021.9465563 · Cited by 9
Multiplex Fragment Analysis Identifies SARS-CoV-2 Variants
Clark, A. E., Wang, Z.-H., Cantarel, B., et al. (2021) · medRxiv · doi:10.1101/2021.04.15.21253747 · Cited by 7
Zhang, S., Bi, G., Wang, X., Yang, Y., Qi, J., Li, S., Mao, X., Peng, R., & Yang, P. (2021) · medRxiv · doi:10.1101/2021.03.10.21252748 · Cited by 6
“Intervention intensity was assumed within the interval [3-15], gave with a relatively accurate estimation of COVID-19 breakouts.”
MethodNemudryi, A., Nemudraia, A., Wiegand, T., et al. (2021) · medRxiv · doi:10.1101/2021.02.22.21252253 · Cited by 7
Pressing Questions and Challenges in the HIV-1 and SARS-CoV-2 Syndemic
Montano, M. A. (2021) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2021.0005 · Cited by 7
“Although error-correcting capacity limits SARS-CoV-2 diversity, variants of concern (VOCs) are emerging with the potential for viral escape mutants (e.g., positions E484 and N501) 146,147 and altered phenotypes (e.g., D614G, 148 B.1.1.7, 149 and P.1 150 ).”
InfluentialPanovska‐Griffiths, J., Stuart, R. M., Kerr, C. C., et al. (2021) · medRxiv · doi:10.1101/2021.02.07.21251287 · Cited by 7
“Unlike our previous work [19-20] where we modelled one strain of the SARS-CoV-2, here we have modelled the implications of two strains of the virus by simulating a single strain with time-varying infectiousness.”
BackgroundMethodInfluentialModelling pooling strategies for SARS-CoV-2 testing in a university setting
Hemani, G., Thomas, A., Walker, J. G., et al. (2021) · medRxiv · doi:10.1101/2021.01.19.20248560 · Cited by 7
Tiered social distancing policies and epidemic control
Bliman, P., Magli, A. C., d’Onofrio, A., & Manfredi, P. (2022) · Proceedings of the Royal Society A Mathematical Physical and Engineering Sciences · doi:10.1098/rspa.2022.0175 · Cited by 5
“These include policy suggestions and identify pitfalls and undesired outcomes, such as a worsening of epidemic control, that can arise following such types of approaches to epidemic responses.”
Detection of the Omicron SARS-CoV-2 Lineage and Its BA.1 Variant with Multiplex RT-qPCR
Yolshin, N. D., Komissarov, A. B., Вадимович, В. К., Даировна, М. Т., Fadeev, A. V., & Lioznov, D. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416153 · Cited by 10
SARS-CoV-2 variants and pregnant Women: A cause for Concern?
Chionuma, J. O., Onyeaka, H. N., Ekwebelem, O. C., & Nnaji, N. D. (2022) · Vaccine X · doi:10.1016/j.jvacx.2022.100185 · Cited by 7
“[19] The implication of these findings on the impact of the disease on the population and specifically pregnancy thus raises concern.”
Structural and functional integrity of decontaminated N95 respirators: Experimental results
Sharma, S. K., Wang, F., Kumar, S., Nawal, R. R., Kumar, P., Yadav, S., Szenti, I., Kukovecz, Á., Schiller, U. D., & Rawal, A. (2022) · Journal of Industrial Textiles · doi:10.1177/15280837221082322 · Cited by 5
Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa
Okoh, O. S., Nii-Trebi, N. I., Jakkari, A., Olaniran, T. T., Senbadejo, T. Y., Kafintu-kwashie, A. A., Dairo, E. O., Ganiyu, T. O., Akaninyene, I. E., Ezediuno, L. O., et al. (2022) · iScience · doi:10.1016/j.isci.2022.103880 · Cited by 13
“Almost simultaneously, the independent emergence of the VOC 20C/501Y.V2 belonging to Pango lineage B.1.351, or Beta VOC was detected in South Africa (Tegally et al., 2021).”
InfluentialPageaud, S., Pothier, C., Rigotti, C., Eyraud-Loisel, A., Bertoglio, J. P., Bienvenüe, A., Leboisne, N., Ponthus, N., Gauchon, R., Gueyffier, F., et al. (2021) · Vaccines · doi:10.3390/vaccines9121462 · Cited by 5
“On 14 December 2020, the Alpha variant (lineage B.1.1.7) was identified in the United Kingdom [2], whereas, in France, the first case was identified by the end of December.”
BackgroundInfluentialGenome sequencing of SARS-CoV-2 reveals the prevalence of variant B 1.1.7 in Egypt
Seadawy, M. G., Gad, A. F., Abo-Elmaaty, S. A., & Hassan, M. G. (2021) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2021.105191 · Cited by 7
“Controlling COVID-19 can be enhanced by vaccination, separating from others socially, general cleanliness, and a large number of diagnostic tests (Voysey et al., 2021; Ferretti et al., 2020).”
Osnes, M. N., Alfsnes, K., Bråte, J., García, I., Riis, R. K., Instefjord, K. H., Elshaug, H., Vollan, H. S., Moen, L. V., Pedersen, B. N., et al. (2021) · Virus Evolution · doi:10.1093/ve/veab086 · Cited by 11
“In response to early reports of B.1.1.7 being more transmissible (Volz et al. 2021) and possibly more virulent, strict border restrictions were implemented in the second half of January 2021.”
InfluentialVesper, N., Ortiz, Y. M., Bartels-Burgahn, F., Yang, J., de la Rosa, K., Tenbusch, M., Schulz, S. R., Finzel, S., Jäck, H., Eibel, H., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.730766 · Cited by 6
“Thus, during the corona pandemic, several SARS-CoV-2 variants have emerged that became dominant in different world regions (33).”
BackgroundCOVID-19 Case Rates in the UK: Modelling Uncertainties as Lockdown Lifts
Brereton, C. F., & Pedercini, M. (2021) · Systems · doi:10.3390/systems9030060 · Cited by 7
“7, now known as the Alpha variant, which was measured as 35% more contagious (95% CI 2–69%) [31,32] and then the ‘Delta variant’, assumed to be twice as contagious as the original virus.”
BackgroundCoordinating SARS-CoV-2 genomic surveillance in the United States
Nelson, M. I., & Thielen, P. (2021) · Virus Evolution · doi:10.1093/ve/veab053 · Cited by 5
“7 variants in the UK in December 2020 (Volz et al. 2021).”
BackgroundInfluentialInfluence of age on the spread of SARS-CoV-2 variant B.1.1.7
Dimeglio, C., Nicot, F., Miédougé, M., Chappert, J.-L., Donnadieu, C., & Izopet, J. (2021) · Journal of Clinical Virology · doi:10.1016/j.jcv.2021.104872 · Cited by 4
Sjaarda, C. P., Guthrie, J. L., Mubareka, S., Simpson, J. T., Hamelin, B., Wong, H., Mortimer, L. M., Slinger, R., McArthur, A. G., Desjardins, M., et al. (2021) · mSphere · doi:10.1128/msphere.00011-21 · Cited by 6
Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants
Kühn, M. J., Abele, D., Binder, S. C., et al. (2021) · medRxiv · doi:10.1101/2021.04.23.21255995 · Cited by 6
“7 [4], previous mitigation strategies have to be reconsidered and strengthened.”
BackgroundRapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
DeWitt, M. E. (2021) · medRxiv · doi:10.1101/2021.02.07.21251291 · Cited by 6
Tang, H., Ke, Y., Wang, L., Wu, M., Sun, T., & Zhu, J. (2022) · Pharmaceuticals · doi:10.3390/ph15081002 · Cited by 4
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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