Imperial College London

DrErikVolz

Faculty of MedicineSchool of Public Health

Reader in Population Biology of Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 7594 1933e.volz Website

 
 
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Location

 

UG10Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

144 results found

Vohringer HS, Sanderson T, Sinnott M, De Maio N, Thuy N, Goater R, Schwach F, Harrison I, HeHowells J, Ariani C, Goncalves S, Jackson DK, Johnstone I, Jung AW, Saint C, Sillitoe J, Suciu M, Goldman N, Panovska-Griffiths J, Birney E, Volz E, Funk S, Kwiatkowski D, Chand M, Martincorena I, Barrett JC, Gerstung Met al., 2021, Genomic reconstruction of the SARS-CoV-2 epidemic in England, NATURE, Vol: 600, Pages: 506-+, ISSN: 0028-0836

Journal article

Ferguson N, Ghani A, Cori A, Hogan A, Hinsley W, Volz Eet al., 2021, Report 49: Growth, population distribution and immune escape of Omicron in England

To estimate the growth of the Omicron variant of concern (1) and its immune escape (2–9) characteristics, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel. We undertook separate analyses according to two case definitions. For the first definition, we included all cases with a definitive negative S-gene Target Failure (SGTF) result and specimen dates between 29/11/2021 and 11/12/2021 inclusive. For the second definition, we included cases with a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive. We chose a later start date for the SGTF definition to ensure greater specificity of SGTF for Omicron.We used logistic and Poisson regression to identify factors associated with testing positive for Omicron compared to non-Omicron (mostly Delta) cases. We explored the following predictors: day, region, symptomatic status, sex, ethnicity, age band and vaccination status. Our results suggest rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (95% CI: 0.33-0.35) [2.0 day doubling time] over the study period from both SGTF and genotype data. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta.Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta.To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection we used conditional Poisson regression to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting our analysis to symptomatic cases and matching by da

Report

Helekal D, Ledda A, Volz E, Wyllie D, Didelot Xet al., 2021, Bayesian Inference of Clonal Expansions in a Dated Phylogeny, SYSTEMATIC BIOLOGY, ISSN: 1063-5157

Journal article

Sonabend R, Whittles LK, Imai N, Perez Guzman PN, Knock E, Rawson T, Gaythorpe KA, Djaafara A, Hinsley W, Fitzjohn R, Lees JA, Thekke Kanapram D, Volz E, Ghani A, Ferguson NM, Baguelin M, Cori Aet al., 2021, Non-pharmaceutical interventions, vaccination, and the SARS-CoV-2 delta variant in England: a mathematical modelling study, The Lancet, Vol: 398, Pages: 1825-1835, ISSN: 0140-6736

Background:England's COVID-19 roadmap out of lockdown policy set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued, with step one starting on March 8, 2021. In this study, we assess the roadmap, the impact of the delta (B.1.617.2) variant of SARS-CoV-2, and potential future epidemic trajectories.Methods:This mathematical modelling study was done to assess the UK Government's four-step process to easing lockdown restrictions in England, UK. We extended a previously described model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the delta variant. We calibrated the model to English surveillance data, including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs. We estimated the resulting number of daily infections and hospital admissions, and daily and cumulative deaths. Three scenarios spanning a range of optimistic to pessimistic vaccine effectiveness, waning natural immunity, and cross-protection from previous infections were investigated. We also considered three levels of mixing after the lifting of restrictions.Findings:The roadmap policy was successful in offsetting the increased transmission resulting from lifting NPIs starting on March 8, 2021, with increasing population immunity through vaccination. However, because of the emergence of the delta variant, with an estimated transmission advantage of 76% (95% credible interval [95% CrI] 69–83) over alpha, fully lifting NPIs on June 21, 2021, as originally planned might have led to 3900 (95% CrI 1500–5700) peak daily hospital admissions under our central parameter scenario. Delaying until July 19, 2021, reduced peak hospital admissions by three fol

Journal article

Kraemer MUG, Hill V, Ruis C, Dellicour S, Bajaj S, McCrone JT, Baele G, Parag KV, Battle AL, Gutierrez B, Jackson B, Colquhoun R, O'Toole Á, Klein B, Vespignani A, COVID-19 Genomics UK CoG-UK consortium, Volz E, Faria NR, Aanensen D, Loman NJ, du Plessis L, Cauchemez S, Rambaut A, Scarpino SV, Pybus OGet al., 2021, Spatiotemporal invasion dynamics of SARS-CoV-2 lineage B.1.1.7 emergence, Science, Vol: 373, Pages: 889-895, ISSN: 0036-8075

Understanding the causes and consequences of the emergence of SARS-CoV-2 variants of concern is crucial to pandemic control yet difficult to achieve, as they arise in the context of variable human behavior and immunity. We investigate the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based PCR data. We identify a multi-stage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explore how B.1.1.7 spread was shaped by non-pharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.

Journal article

Didelot X, Geidelberg L, COVID-19 Genomics UK COG-UK consortium, Volz EMet al., 2021, Model design for non-parametric phylodynamic inference and applications to pathogen surveillance., bioRxiv

Inference of effective population size from genomic data can provide unique information about demographic history, and when applied to pathogen genetic data can also provide insights into epidemiological dynamics. The combination of non-parametric models for population dynamics with molecular clock models which relate genetic data to time has enabled phylodynamic inference based on large sets of time-stamped genetic sequence data. The methodology for non-parametric inference of effective population size is well-developed in the Bayesian setting, but here we develop a frequentist approach based on non-parametric latent process models of population size dynamics. We appeal to statistical principles based on out-of-sample prediction accuracy in order to optimize parameters that control shape and smoothness of the population size over time. We demonstrate the flexibility and speed of this approach in a series of simulation experiments, and apply the methodology to reconstruct the previously described waves in the seventh pandemic of cholera. We also estimate the impact of non-pharmaceutical interventions for COVID-19 in England using thousands of SARS-CoV-2 sequences. By incorporating a measure of the strength of these interventions over time within the phylodynamic model, we estimate the impact of the first national lockdown in the UK on the epidemic reproduction number.

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan TA, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason GP, Ratmann O, Semenova E, Leech G, Sandkuehler JF, Rogers-Smith C, Vollmer M, Unwin HJT, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson NM, Bhatt S, Brauner JM, Flaxman Set al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England, EClinicalMedicine, Vol: 39, Pages: 1-8, ISSN: 2589-5370

BackgroundSince its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital.MethodsWe examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021.FindingsAcross data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May.InterpretationThe outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control effortsFundingNational Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy

Journal article

Helekal D, Ledda A, Volz E, Wyllie D, Didelot Xet al., 2021, Bayesian inference of clonal expansions in a dated phylogeny

<jats:title>ABSTRACT</jats:title><jats:p>Microbial population genetics models often assume that all lineages are constrained by the same population size dynamics over time. However, many neutral and selective events can invalidate this assumption, and can contribute to the clonal expansion of a specific lineage relative to the rest of the population. Such differential phylodynamic properties between lineages result in asymmetries and imbalances in phylogenetic trees that are sometimes described informally but which are difficult to analyse formally. To this end, we developed a model of how clonal expansions occur and affect the branching patterns of a phylogeny. We show how the parameters of this model can be inferred from a given dated phylogeny using Bayesian statistics, which allows us to assess the probability that one or more clonal expansion events occurred. For each putative clonal expansion event we estimate their date of emergence and subsequent phylodynamic trajectories, including their long-term evolutionary potential which is important to determine how much effort should be placed on specific control measures. We demonstrate the applicability of our methodology on simulated and real datasets.</jats:p>

Journal article

Dennis AM, Frost SDW, Enders K, Cressman AE, Volz E, Adams N, Miller WC, Cohen MS, Mobley V, Samoff E, Eron JJet al., 2021, HIV-1 Transmission linkages among persons with incident infection to inform public health surveillance, ECLINICALMEDICINE, Vol: 37

Journal article

Meng B, Kemp SA, Papa G, Datir R, Ferreira IATM, Marelli S, Harvey WT, Lytras S, Mohamed A, Gallo G, Thakur N, Collier DA, Mlcochova P, Duncan LM, Carabelli AM, Kenyon JC, Lever AM, De Marco A, Saliba C, Culap K, Cameroni E, Matheson NJ, Piccoli L, Corti D, James LC, Robertson DL, Bailey D, Gupta RKet al., 2021, Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7, CELL REPORTS, Vol: 35, ISSN: 2211-1247

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan T, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason G, Ratmann O, Leech G, Fabienne Sandkühler J, Rogers-Smith C, Vollmer M, Unwin H, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson N, Bhatt S, Brauner J, Flaxman Set al., 2021, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Publisher: Imperial College London, 44

Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when, whether, and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. This is particularly true for England, which has high coverage from vaccines that are likely more protective against B.1.1.7 than some other VOCs. We examine trends in B.1.1.7’s prevalence in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. Our results suggest shifts in the composition of SARS-CoV-2 lineages driving transmission in England between March and April 2021. Local transmission of non-B.1.1.7 VOCs may be increasing; this warrants urgent further investigation.

Report

Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, O'Toole Á, Amato R, Ragonnet-Cronin M, Harrison I, Jackson B, Ariani CV, Boyd O, Loman NJ, McCrone JT, Gonçalves S, Jorgensen D, Myers R, Hill V, Jackson DK, Gaythorpe K, Groves N, Sillitoe J, Kwiatkowski DP, COVID-19 Genomics UK COG-UK consortium, Flaxman S, Ratmann O, Bhatt S, Hopkins S, Gandy A, Rambaut A, Ferguson NMet al., 2021, Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England, Nature, Vol: 593, Pages: 266-269, ISSN: 0028-0836

The SARS-CoV-2 lineage B.1.1.7, designated a Variant of Concern 202012/01 (VOC) by Public Health England1, originated in the UK in late Summer to early Autumn 20202. Whole genome SARS-CoV-2 sequence data collected from community-based diagnostic testing shows an unprecedentedly rapid expansion of the B.1.1.7 lineage during Autumn 2020, suggesting a selective advantage. 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. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Time-varying reproduction numbers for the VOC and cocirculating lineages were estimated using SGTF and genomic data. The best supported models did not indicate a substantial difference in VOC transmissibility among different age groups. There is a consensus among all analyses that the VOC has a substantial transmission advantage with a 50% to 100% higher reproduction number.

Journal article

Eales O, Page AJ, Tang S, Walters C, Wang H, Haw D, Trotter AJ, Viet TL, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly C, O'Grady J, Volz E, The COVID-19 Genomics UK Consortium, Darzi A, Ward H, Elliott P, Riley Set al., 2021, SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples

Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.

Working paper

Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, Kläser K, Canas LS, Molteni E, Modat M, Drew DA, Nguyen LH, Polidori L, Selvachandran S, Hu C, Capdevila J, COVID-19 Genomics UK COG-UK Consortium, Hammers A, Chan AT, Wolf J, Spector TD, Steves CJ, Ourselin Set al., 2021, Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study, The Lancet Public Health, Vol: 6, Pages: e335-e345, ISSN: 2468-2667

BACKGROUND: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. METHODS: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. FINDINGS: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in repo

Journal article

Ragonnet-Cronin M, Boyd O, Geidelberg L, Jorgensen D, Nascimento F, Siveroni I, Johnson R, Baguelin M, Cucunuba Z, Jauneikaite E, Mishra S, Watson O, Ferguson N, Cori A, Donnelly C, Volz Eet al., 2021, Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions, Nature Communications, Vol: 12, Pages: 1-7, ISSN: 2041-1723

Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non- pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced 30 much less severe COVID-19 morbidity and mortality during the period of study.

Journal article

Kemp SA, Collier DA, Datir RP, Ferreira IATM, Gayed S, Jahun A, Hosmillo M, Rees-Spear C, Mlcochova P, Lumb IU, Roberts DJ, Chandra A, Temperton N, Sharrocks K, Blane E, Modis Y, Leigh KE, Briggs JAG, van Gils MJ, Smith KGC, Bradley JR, Smith C, Doffinger R, Ceron-Gutierrez L, Barcenas-Morales G, Pollock DD, Goldstein RA, Smielewska A, Skittrall JP, Gouliouris T, Goodfellow IG, Gkrania-Klotsas E, Illingworth CJR, McCoy LE, Gupta RKet al., 2021, SARS-CoV-2 evolution during treatment of chronic infection, NATURE, Vol: 592, Pages: 277-+, ISSN: 0028-0836

Journal article

Li X, Liu H, Rife Magalis B, Pond SLK, Volz EMet al., 2021, Molecular Evolution of Human Norovirus GII.2 Clusters, FRONTIERS IN MICROBIOLOGY, Vol: 12

Journal article

Aggarwal D, Page AJ, Schaefer U, Savva GM, Myers R, Volz E, Ellaby N, Platt S, Groves N, Gallaghar E, Tumelty NM, Le Viet T, Hughes GJ, Chen C, Turner C, Logan S, Harrison A, Peacock SJ, Chand M, Harrison EMet al., 2021, An integrated analysis of contact tracing and genomics to assess the efficacy of travel restrictions on SARS-CoV-2 introduction and transmission in England from June to September, 2020

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Mitigation of SARS-CoV-2 transmission from international travel is a priority. Travellers from countries with travel restrictions (closed travel-corridors) were required to quarantine for 14 days over Summer 2020 in England. We describe the genomic epidemiology of travel-related cases in England and evaluate the effectiveness of this travel policy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Between 27/05/2020 and 13/09/2020, probable travel-related SARS-CoV-2 cases and their contacts were identified and combined with UK SARS-CoV-2 sequencing data. The epidemiology and demographics of cases was identified, and the number of contacts per case modelled using negative binomial regression to estimate the effect of travel restriction, and any variation by age, sex and calendar date. Unique travel-related SARS-CoV-2 genomes in the COG-UK dataset were identified to estimate the effect travel restrictions on cluster size generated from these. The Polecat Clustering Tool was used to identify a travel-related SARS-CoV-2 cluster of infection.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>4,207 travel-related SARS-CoV-2 cases are identified. 51.2% (2155/4207) of cases reported travel to one of three countries; 21.0% (882) Greece, 16.3% (685) Croatia and 14.0% (589) Spain. Median number of contacts per case was 3 (IQR 1-5), and greatest for the 16-20 age-group (9.0, 95% C.I.=5.6-14.5), which saw the largest attenuation by travel restriction. Travel restriction was associated with a 40% (rate ratio=0.60, 95% C.I.=0.37-0.95) lower rate of contacts. 827/4207 (19.7%) of cases had high-quality SARS-CoV-2 genomes available. Fewer genomically-linked cases were observed for index cases related to countries with travel restrictions compared to cases

Journal article

Smith TP, Dorigatti I, Mishra S, Volz E, Walker PGT, Ragonnet-Cronin M, Tristem M, Pearse WDet al., 2021, Environmental drivers of SARS-CoV-2 lineage B.1.1.7 transmission intensity

<jats:title>Abstract</jats:title><jats:p>Previous work has shown that environment affects SARS-CoV-2 transmission, but it is unclear whether emerging strains show similar responses. Here we show that, like other SARS-CoV-2 strains, lineage B.1.1.7 spread with greater transmission in colder and more densely populated parts of England. However, we also find evidence of B.1.1.7 having a transmission advantage at warmer temperatures compared to other strains. This implies that spring and summer conditions are unlikely to slow B.1.1.7’s invasion in Europe and across the Northern hemisphere - an important consideration for public health interventions.</jats:p>

Journal article

Mishra S, Flaxman S, Volz E, Johnson R, Geidelberg L, Hinsley WR, Ratmann O, Bhatt S, Gandy A, Rambaut A, Ferguson NMet al., 2021, mrc-ide/sarscov2-b.1.1.7: Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

Code for our nature paper Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

Software

Ferreira Do Nascimento F, Volz E, Siveroni I, 2021, thednainus/sarscov2simulations: version 1.0.0 of R package sarscov2simulations

Functions to simulate coalescent trees based on structured coalescent models. This package also contains functions to simulate sequence data based on phylogenetic trees.

Software

Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, NASCIMENTO F, Fitzjohn R, Gaythorpe K, Geidelberg L, green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2021, Reduction in mobility and COVID-19 transmission, Nature Communications, Vol: 12, ISSN: 2041-1723

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

Journal article

du Plessis L, McCrone JT, Zarebski AE, Hill V, Ruis C, Gutierrez B, Raghwani J, Ashworth J, Colquhoun R, Connor TR, Faria NR, Jackson B, Loman NJ, O'Toole A, Nicholls SM, Parag K, Scher E, Vasylyeva T, Volz EM, Watts A, Bogoch II, Khan K, Aanensen DM, Kraemer MUG, Rambaut A, Pybus OGet al., 2021, Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK, SCIENCE, Vol: 371, Pages: 708-+, ISSN: 0036-8075

Journal article

Volz E, Hill V, McCrone J, Price A, Jorgensen D, O'Toole A, Southgate JA, Johnson R, Jackson B, Nascimento F, Rey S, Nicholls S, Colquhoun R, da Silva Filipe A, Shepherd J, Pascall D, Shah R, Jesudason N, Li K, Jarrett R, Pacchiarini N, Bull M, Geidelberg L, Siveroni I, Goodfellow I, Loman NJ, Pybus O, Robertson D, Thomson E, Rambaut A, Connor T, The COVID-19 Genomics UK Consortiumet al., 2021, Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity, Cell, Vol: 184, Pages: 64-75.e11, ISSN: 0092-8674

In February 2020 a substitution at the interface between SARS-CoV-2 Spike protein subunits, Spike D614G, was observed in public databases. The Spike 614G variant subsequently increased in frequency in many locations throughout the world. Global patterns of dispersal of Spike 614G are suggestive of a selective advantage of this variant, however the origin of Spike 614G is associated with early colonization events in Europe and subsequent radiations to the rest of the world. Increasing frequency of 614G may therefore be due to a random founder effect. We investigate the hypothesis for positive selection of Spike 614G at the level of an individual country, the United Kingdom, using more than 25,000 whole genome SARS-CoV-2 sequences collected by COVID-19 Genomics UK Consortium. Using phylogenetic analysis, we identify Spike 614G and 614D clades with unique origins in the UK and from these we extrapolate and compare growth rates of co-circulating transmission clusters. We find that Spike 614G clusters are introduced in the UK later on average than 614D clusters and grow to larger size after adjusting for time of introduction. Phylodynamic analysis does not show a significant increase in growth rates for clusters with the 614G variant, but population genetic modelling indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We also investigate the potential influence of Spike 614D versus G on virulence by matching a subset of records to clinical data on patient outcomes. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality, but younger patients have slightly increased odds of 614G carriage. Despite the availability of a very large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of higher transmission rate for 614G, but significant differences in growth, size, and composition of these lineages indicate a need

Journal article

Geidelberg L, Boyd O, Jorgensen D, Siveroni I, Nascimento FF, Johnson R, Ragonnet-Cronin M, Fu H, Wang H, Xi X, Chen W, Liu D, Chen Y, Tian M, Tan W, Zai J, Sun W, Li J, Li J, Volz E, Li X, Nie Qet al., 2021, Genomic epidemiology of a densely sampled COVID-19 outbreak in China, Virus Evolution, Vol: 7, Pages: 1-7, ISSN: 2057-1577

Analysis of genetic sequence data from the SARS-CoV-2 pandemic can provide insights into epidemic origins, worldwide dispersal, and epidemiological history. With few exceptions, genomic epidemiological analysis has focused on geographically distributed data sets with few isolates in any given location. Here we report an analysis of 20 whole SARS- CoV-2 genomes from a single relatively small and geographically constrained outbreak in Weifang, People’s Republic of China. Using Bayesian model-based phylodynamic methods, we estimate a mean basic reproduction number (R0) of 3.4 (95% highest posterior density interval: 2.1-5.2) in Weifang, and a mean effective reproduction number (Rt ) that falls below 1 on February 4th. We further estimate the number of infections through time and compare these estimates to confirmed diagnoses by the Weifang Centers for Disease Control. We find that these estimates are consistent with reported cases and there is unlikely to be a large undiagnosed burden of infection over the period we studied.

Journal article

Fu H, Wang H, Xi X, Boonyasiri A, Wang Y, Hinsley W, Fraser KJ, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewé T, Dighe A, Winskill P, van Elsland SL, Ainslie KEC, Baguelin M, Bhatt S, Boyd O, Brazeau NF, Cattarino L, Charles G, Coupland H, Cucunubá ZM, Cuomo-Dannenburg G, Donnelly CA, Dorigatti I, Eales OD, Fitzjohn RG, Flaxman S, Gaythorpe KAM, Ghani AC, Green WD, Hamlet A, Hauck K, Haw DJ, Jeffrey B, Laydon DJ, Lees JA, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag KV, Ragonnet-Cronin M, Riley S, Schmit N, Thompson HA, Unwin HJT, Verity R, Vollmer MAC, Volz E, Walker PGT, Walters CE, Waston OJ, Whittaker C, Whittles LK, Imai N, Bhatia S, Ferguson NMet al., 2021, A database for the epidemic trends and control measures during the first wave of COVID-19 in mainland China, International Journal of Infectious Diseases, Vol: 102, Pages: 463-471, ISSN: 1201-9712

Objectives: This data collation effort aims to provide a comprehensive database to describe the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19)across main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data on the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted a descriptive analysis of the epidemics in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends were different across provinces. Compared to Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as local transmission of COVID-19 declined, switching the focus of measures to testing and quarantine of inbound travellers could help to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database with these indicators and information on control measures provides useful source for exploring further research and policy planning for response to the COVID-19 epidemic.

Journal article

Didelot X, Siveroni I, Volz EM, 2021, Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies, Molecular Biology and Evolution, Vol: 38, Pages: 307-317, ISSN: 0737-4038

Phylogenetic dating is one of the most powerful and commonly used methods of drawing epidemiological interpretations from pathogen genomic data. Building such trees requires considering a molecular clock model which represents the rate at which substitutions accumulate on genomes. When the molecular clock rate is constant throughout the tree then the clock is said to be strict, but this is often not an acceptable assumption. Alternatively, relaxed clock models consider variations in the clock rate, often based on a distribution of rates for each branch. However, we show here that the distributions of rates across branches in commonly used relaxed clock models are incompatible with the biological expectation that the sum of the numbers of substitutions on two neighbouring branches should be distributed as the substitution number on a single branch of equivalent length. We call this expectation the additivity property. We further show how assumptions of commonly used relaxed clock models can lead to estimates of evolutionary rates and dates with low precision and biased confidence intervals. We therefore propose a new additive relaxed clock model where the additivity property is satisfied. We illustrate the use of our new additive relaxed clock model on a range of simulated and real datasets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.

Journal article

Grassly NC, Pons-Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Teamet al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099

BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines

Journal article

Maurano MT, Ramaswami S, Zappile P, Dimartino D, Boytard L, Ribeiro-dos-Santos AM, Vulpescu NA, Westby G, Shen G, Feng X, Hogan MS, Ragonnet-Cronin M, Geidelberg L, Marier C, Meyn P, Zhang Y, Cadley J, Ordonez R, Luther R, Huang E, Guzman E, Arguelles-Grande C, Argyropoulos KV, Black M, Serrano A, Call ME, Kim MJ, Belovarac B, Gindin T, Lytle A, Pinnell J, Vougiouklakis T, Chen J, Lin LH, Rapkiewicz A, Raabe V, Samanovic MI, Jour G, Osman I, Aguero-Rosenfeld M, Mulligan MJ, Volz EM, Cotzia P, Snuderl M, Heguy Aet al., 2020, Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City region, GENOME RESEARCH, Vol: 30, ISSN: 1088-9051

Journal article

Thompson H, Imai N, Dighe A, Ainslie K, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Donnelly C, Ferguson Net al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982

We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.

Journal article

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