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

107 results found

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, Sandkühler 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 S, COVID-19 Genomics UK COG-UK Consortiumet al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England., EClinicalMedicine, Vol: 39

Background: Since 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. Methods: We 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. Findings: Across 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. Interpretation: The 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 efforts. Funding: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open

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

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

<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 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 usefulness 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

Background: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. Methods: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014-2018) and past (<2014) HIV diagnoses. IHI were defined as documented acute infections or seroconversion. Demographic and virologic features of HIV genetic clusters (<1.5% pairwise genetic distance) involving ≥ 1 IHI were assessed. Persons with viral genetic links and who had diagnoses >90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. Findings: Of 4,405 HIV diagnoses 2014-2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68% <30 years), and reported sex with men (MSM) risk (79%). Index persons were more likely to be cluster members compared to non-index persons diagnosed during the same period (72% vs. 49%). In total, 162 clusters were identified involving 233 IHI, 577 recent diagnoses, and 163 past diagnoses. Most IHI cases (53%) had viral linkages to ≥1 previously diagnosed person without evidence of HIV viral suppression in the year prior to the diagnosis of the IHI index. In contact tracing, only 53% IHI cases named an HIV-positive contact, resulting in 0.5 previously diagnosed persons detected per IHI investigated. When combined with viral analyses, the detection rate of viremic previously diagnosed persons increased to 1.3. Interpretation: Integrating public health with molecular epidemiology, revealed that more than half of IHI have viral links to persons with previously diagnosed unsuppressed HIV infection which was largely unrecognized by traditional contact tracing. Enhanced partner services to support engagement and retention in HIV care and improved case

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, Robson SC, Loman NJ, Connor TR, Golubchik T, Martinez Nunez RT, Ludden C, Corden S, Johnston I, Bonsall D, Smith CP, Awan AR, Bucca G, Torok ME, Saeed K, Prieto JA, Jackson DK, Hamilton WL, Snell LB, Moore C, Harrison EM, Goncalves S, Fairley DJ, Loose MW, Watkins J, Livett R, Moses S, Amato R, Nicholls S, Bull M, Smith DL, Barrett J, Aanensen DM, Curran MD, Parmar S, Aggarwal D, Shepherd JG, Parker MD, Glaysher S, Bashton M, Underwood AP, Pacchiarini N, Loveson KF, Templeton KE, Langford CF, Sillitoe J, de Silva TI, Wang D, Kwiatkowski D, Rambaut A, O'Grady J, Cottrell S, Holden MTG, Thomson EC, Osman H, Andersson M, Chauhan AJ, Hassan-Ibrahim MO, Lawniczak M, Alderton A, Chand M, Constantinidou C, Unnikrishnan M, Darby AC, Hiscox JA, Paterson S, Martincorena I, Volz EM, Page AJ, Pybus OG, Bassett AR, Ariani CV, Chapman MHS, Li KK, Shah RN, Jesudason NG, Taha Y, McHugh MP, Dewar R, Jahun AS, McMurray C, Pandey S, McKenna JP, Nelson A, Young GR, McCann CM, Elliott S, Lowe Het 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

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Journal article

Ragonnet-Cronin M, Golubchik T, Moyo S, Fraser C, Essex M, Novitsky V, Volz Eet al., 2021, HIV genetic diversity informs stage of HIV-1 infection among patients receiving antiretroviral therapy in Botswana, The Journal of Infectious Diseases, ISSN: 0022-1899

BackgroundHIV-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However the effect of antiretroviral treatment (ART) on the inference remains unknown.MethodsParticipants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n=1944). Full-length HIV genome sequencing was performed from proviral DNA. We optimized a machine learning model to classify infections as < or >1 year based on viral genetic diversity, demographic and clinical data.ResultsThe best predictive model included variables for genetic diversity of HIV-1 gag, pol and env, viral load, age, sex and ART status. Most participants were on ART. Balanced accuracy was 90.6% (95%CI:86.7%-94.1%). We tested the algorithm among newly diagnosed participants with or without documented negative HIV tests. Among those without records, those who self-reported a negative HIV test within <1 year were more frequently classified as recent than those who reported a test >1 year previously. There was no difference in classification between those self-reporting a negative HIV test <1 year, whether or not they had a record.ConclusionsThese results indicate that recency of HIV-1 infection can be inferred from viral sequence diversity even among patients on suppressive ART.

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, CITIID-NIHR BioResource COVID-19 Collaboration, COVID-19 Genomics UK COG-UK Consortium, 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: 277-282

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing an

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, ISSN: 1664-302X

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

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

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

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

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

Fountain-Jones NM, Appaw RC, Carver S, Didelot X, Volz E, Charleston Met al., 2020, Emerging phylogenetic structure of the SARS-CoV-2 pandemic., Virus Evol, Vol: 6, ISSN: 2057-1577

Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity and whether it reveals epidemiological insights are fundamental questions for understanding the evolutionary trajectory of this virus. Here, we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Non-synonymous mutations that characterize Lineage C occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.

Journal article

Okell LC, Verity R, Katzourakis A, Volz EM, Watson OJ, Mishra S, Walker P, Whittaker C, Donnelly CA, Riley S, Ghani AC, Gandy A, Flaxman S, Ferguson NM, Bhatt Set al., 2020, Host or pathogen-related factors in COVID-19 severity? Reply, LANCET, Vol: 396, Pages: 1397-1397, ISSN: 0140-6736

Journal article

Poletto C, Scarpino SV, Volz EM, 2020, Applications of predictive modelling early in the COVID-19 epidemic., The Lancet Digital Health, Vol: 2, Pages: e498-e499, ISSN: 2589-7500

Journal article

Hogan A, Winskill P, Watson O, Walker P, Whittaker C, Baguelin M, Haw D, Lochen A, Gaythorpe K, Ainslie K, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Donnelly C, Dorigatti I, Eales O, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Flaxman S, Green W, Hallett T, Hamlet A, Hinsley W, Imai N, Jauneikaite E, Jeffrey B, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Ower A, Parag K, Ragonnet-Cronin M, Siveroni I, Skarp J, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Xi X, Muhib F, Smith P, Hauck K, Ferguson N, Ghani Aet al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.

Report

van Elsland S, Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Donnelly C, Dorigatti I, Eales O, van Elsland S, Nascimento F, Fitzjohn R, Flaxman S, Forna A, Fu H, Gaythorpe K, Green W, Hamlet A, Hauck K, Haw D, Hayes S, Hinsley W, Imai N, Jeffrey B, Johnson R, Jorgensen D, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Olivera Mesa D, Pons Salort M, Ragonnet-Cronin M, Siveroni I, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Winskill P, Xi X, Ferguson N, Beals E, Walker P, Anonymous Authorset al., 2020, Report 31: Estimating the burden of COVID-19 in Damascus, Syria: an analysis of novel data sources to infer mortality under-ascertainment

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.

Report

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