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Article ; Online: Mutational spectra are associated with bacterial niche

Christopher Ruis / Aaron Weimann / Gerry Tonkin-Hill / Arun Prasad Pandurangan / Marta Matuszewska / Gemma G. R. Murray / Roger C. Lévesque / Tom L. Blundell / R. Andres Floto / Julian Parkhill

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, ... ...

Abstract	Abstract As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to detect both disruption of DNA repair processes and exposure to niche-specific mutagens. Here we reconstruct mutational spectra for 84 clades from 31 diverse bacterial species and find distinct mutational patterns. We extract signatures driven by specific DNA repair defects using hypermutator lineages, and further deconvolute the spectra into multiple signatures operating within different clades. We show that these signatures are explained by both bacterial phylogeny and replication niche. By comparing mutational spectra of clades from different environmental and biological locations, we identify niche-associated mutational signatures, and then employ these signatures to infer the predominant replication niches for several clades where this was previously obscure. Our results show that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes for established and emergent human bacterial pathogens.
Keywords	Science ; Q
Subject code	612
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RhierBAPS

Gerry Tonkin-Hill / John A. Lees / Stephen D. Bentley / Simon D.W. Frost / Jukka Corander

Wellcome Open Research, Vol

An R implementation of the population clustering algorithm hierBAPS [version 1; referees: 2 approved]

2018 Volume 3

Abstract: Identifying structure in collections of sequence data sets remains a common problem in genomics. hierBAPS, a popular algorithm for identifying population structure in haploid genomes, has previously only been available as a MATLAB binary. We provide an R ...

Abstract	Identifying structure in collections of sequence data sets remains a common problem in genomics. hierBAPS, a popular algorithm for identifying population structure in haploid genomes, has previously only been available as a MATLAB binary. We provide an R implementation which is both easier to install and use, automating the entire pipeline. Additionally, we allow for the use of multiple processors, improve on the default settings of the algorithm, and provide an interface with the ggtree library to enable informative illustration of the clustering results. Our aim is that this package aids in the understanding and dissemination of the method, as well as enhancing the reproducibility of population structure analyses.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Producing polished prokaryotic pangenomes with the Panaroo pipeline

Gerry Tonkin-Hill / Neil MacAlasdair / Christopher Ruis / Aaron Weimann / Gal Horesh / John A. Lees / Rebecca A. Gladstone / Stephanie Lo / Christopher Beaudoin / R. Andres Floto / Simon D.W. Frost / Jukka Corander / Stephen D. Bentley / Julian Parkhill

Genome Biology, Vol 21, Iss 1, Pp 1-

2020 Volume 21

Abstract: Abstract Population-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the automated annotation of prokaryotic ... ...

Abstract	Abstract Population-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the automated annotation of prokaryotic genomes is imperfect, and errors due to fragmented assemblies, contamination, diverse gene families and mis-assemblies accumulate over the population, leading to profound consequences when analysing the set of all genes found in a species. Here, we introduce Panaroo, a graph-based pangenome clustering tool that is able to account for many of the sources of error introduced during the annotation of prokaryotic genome assemblies. Panaroo is available at https://github.com/gtonkinhill/panaroo .
Keywords	Bacteria ; Pangenome ; Prokaryote ; Clustering ; Horizontal gene transfer ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 13

Abstract: Enterococcus faecalis is a commensal microorganism of animals, insects and humans, but also a nosocomial pathogen. Here, the authors analyse genomic sequences from E. faecalis isolates from animals and humans, and find that the last common ancestors of ... ...

Abstract	Enterococcus faecalis is a commensal microorganism of animals, insects and humans, but also a nosocomial pathogen. Here, the authors analyse genomic sequences from E. faecalis isolates from animals and humans, and find that the last common ancestors of multiple hospital-associated lineages date to the pre-antibiotic era.
Keywords	Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Common virulence gene expression in adult first-time infected malaria patients and severe cases

eLife, Vol

2021 Volume 10

Abstract: Sequestration of Plasmodium falciparum(P. falciparum)-infected erythrocytes to host endothelium through the parasite-derived P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins is central to the development of malaria pathogenesis. ... ...

Abstract	Sequestration of Plasmodium falciparum(P. falciparum)-infected erythrocytes to host endothelium through the parasite-derived P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins is central to the development of malaria pathogenesis. PfEMP1 proteins have diversified and expanded to encompass many sequence variants, conferring each parasite a similar array of human endothelial receptor-binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32 P. falciparum-infected adult travellers returning to Germany. Patients were categorized into either malaria naive (n = 15) or pre-exposed (n = 17), and into severe (n = 8) or non-severe (n = 24) cases. For differential expression analysis, PfEMP1-encoding var gene transcripts were de novo assembled from RNA-seq data and, in parallel, var-expressed sequence tags were analyzed and used to predict the encoded domain composition of the transcripts. Both approaches showed in concordance that severe malaria was associated with PfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-binding PfEMP1 was linked to non-severe malaria outcomes. First-time infected adults were more likely to develop severe symptoms and tended to be infected for a longer period. Thus, parasites with more pathogenic PfEMP1 variants are more common in patients with a naive immune status, and/or adverse inflammatory host responses to first infections favor the growth of EPCR-binding parasites.
Keywords	P. falciparum ; PfEMP1 ; RNA-seq ; transcriptomics ; variant surface antigens ; virulence ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572 ; 616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism

Chrispin Chaguza / Marie Yang / Jennifer E. Cornick / Mignon du Plessis / Rebecca A. Gladstone / Brenda A. Kwambana-Adams / Stephanie W. Lo / Chinelo Ebruke / Gerry Tonkin-Hill / Chikondi Peno / Madikay Senghore / Stephen K. Obaro / Sani Ousmane / Gerd Pluschke / Jean-Marc Collard / Betuel Sigaùque / Neil French / Keith P. Klugman / Robert S. Heyderman /

Lesley McGee / Martin Antonio / Robert F. Breiman / Anne von Gottberg / Dean B. Everett / Aras Kadioglu / Stephen D. Bentley

Communications Biology, Vol 3, Iss 1, Pp 1-

2020 Volume 12

Abstract: Using a genome-wide association study approach, Chaguza et al. identify significant genotype-phenotype associations relevant to Streptococcus pneumoniae infection. These findings indicate genetic variations in the pathogen attributed to pneumococcal ... ...

Abstract	Using a genome-wide association study approach, Chaguza et al. identify significant genotype-phenotype associations relevant to Streptococcus pneumoniae infection. These findings indicate genetic variations in the pathogen attributed to pneumococcal tropism to central nervous system tissues, with implications for meningitis virulence.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic epidemiology of COVID-19 in care homes in the east of England

William L Hamilton / Gerry Tonkin-Hill / Emily R Smith / Dinesh Aggarwal / Charlotte J Houldcroft / Ben Warne / Luke W Meredith / Myra Hosmillo / Aminu S Jahun / Martin D Curran / Surendra Parmar / Laura G Caller / Sarah L Caddy / Fahad A Khokhar / Anna Yakovleva / Grant Hall / Theresa Feltwell / Malte L Pinckert / Iliana Georgana /

Yasmin Chaudhry / Colin S Brown / Sonia Gonçalves / Roberto Amato / Ewan M Harrison / Nicholas M Brown / Mathew A Beale / Michael Spencer Chapman / David K Jackson / Ian Johnston / Alex Alderton / John Sillitoe / Cordelia Langford / Gordon Dougan / Sharon J Peacock / Dominic P Kwiatowski / Ian G Goodfellow / M Estee Torok / COVID-19 Genomics Consortium UK

eLife, Vol

2021 Volume 10

Abstract: COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the ... ...

Abstract	COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns – outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.
Keywords	COVID-19 ; SARS-CoV-2 ; genomics ; epidemiology ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	360
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Patterns of within-host genetic diversity in SARS-CoV-2

Gerry Tonkin-Hill / Inigo Martincorena / Roberto Amato / Andrew RJ Lawson / Moritz Gerstung / Ian Johnston / David K Jackson / Naomi Park / Stefanie V Lensing / Michael A Quail / Sónia Gonçalves / Cristina Ariani / Michael Spencer Chapman / William L Hamilton / Luke W Meredith / Grant Hall / Aminu S Jahun / Yasmin Chaudhry / Myra Hosmillo /

eLife, Vol

2021 Volume 10

Abstract: Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of ... ...

Abstract	Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.
Keywords	SARS-CoV-2 ; within-host ; mutational spectrum ; transmission ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002–17

Rebecca A Gladstone, PhD / Alan McNally, ProfPhD / Anna K Pöntinen, PhD / Gerry Tonkin-Hill, MSc / John A Lees, PhD / Kusti Skytén, MSc / François Cléon, PhD / Martin O K Christensen, MSc / Bjørg C Haldorsen, MSc / Kristina K Bye, BSc / Karianne W Gammelsrud, PhD / Reidar Hjetland, PhD / Angela Kümmel, MD / Hege E Larsen, BSc / Paul Christoffer Lindemann, MD / Iren H Löhr, MD / Åshild Marvik, PhD / Einar Nilsen, MD / Marie T Noer, MSc /

Gunnar S Simonsen, ProfPhD / Martin Steinbakk, MD / Ståle Tofteland, PhD / Marit Vattøy, BSc / Stephen D Bentley, ProfPhD / Nicholas J Croucher, PhD / Julian Parkhill, ProfPhD / Pål J Johnsen, ProfPhD / Ørjan Samuelsen, ProfPhD / Jukka Corander, ProfPhD

The Lancet Microbe, Vol 2, Iss 7, Pp e331-e

a nationwide, longitudinal, microbial population genomic study

2021 Volume 341

Abstract: Summary: Background: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale ...

Abstract	Summary: Background: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology. Methods: This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22·5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002–10 and 2011–17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. Findings: Of the 3500 isolates requested from the participating laboratories, 3397 (97·1%) were received, of which 3254 (95·8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5·6%) of 1277 in 2002–10 to 207 (10·5%) of 1977 in 2011–17 (p<0·0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum β-lactamase (ESBL)-positive isolates (75 [58·6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39·2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both blaCTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone ...
Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Subject code	580
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7

Mark S Graham, PhD / Carole H Sudre, PhD / Anna May, MA / Michela Antonelli, PhD / Benjamin Murray, MSc / Thomas Varsavsky, MSc / Kerstin Kläser, MSc / Liane S Canas, PhD / Erika Molteni, PhD / Marc Modat, PhD / David A Drew, PhD / Long H Nguyen, MD / Lorenzo Polidori, MSc / Somesh Selvachandran, MSc / Christina Hu, MA / Joan Capdevila, PhD / Alexander Hammers, ProfPhD / Andrew T Chan, ProfMD / Jonathan Wolf, MA /

Tim D Spector, ProfPhD / Claire J Steves, PhD / Sebastien Ourselin, ProfPhD / Cherian Koshy / Amy Ash / Emma Wise / Nathan Moore / Matilde Mori / Nick Cortes / Jessica Lynch / Stephen Kidd / Derek J Fairley / Tanya Curran / James P McKenna / Helen Adams / Christophe Fraser / Tanya Golubchik / David Bonsall / Mohammed O Hassan-Ibrahim / Cassandra S Malone / Benjamin J Cogger / Michelle Wantoch / Nicola Reynolds / Ben Warne / Joshua Maksimovic / Karla Spellman / Kathryn McCluggage / Michaela John / Robert Beer / Safiah Afifi / Sian Morgan / Angela Marchbank / Anna Price / Christine Kitchen / Huw Gulliver / Ian Merrick / Joel Southgate / Martyn Guest / Robert Munn / Trudy Workman / Thomas R Connor / William Fuller / Catherine Bresner / Luke B Snell / Amita Patel / Themoula Charalampous / Gaia Nebbia / Rahul Batra / Jonathan Edgeworth / Samuel C Robson / Angela H Beckett / David M Aanensen / Anthony P Underwood / Corin A Yeats / Khalil Abudahab / Ben EW Taylor / Mirko Menegazzo / Gemma Clark / Wendy Smith / Manjinder Khakh / Vicki M Fleming / Michelle M Lister / Hannah C Howson-Wells / Louise Berry / Tim Boswell / Amelia Joseph / Iona Willingham / Carl Jones / Christopher Holmes / Paul Bird / Thomas Helmer / Karlie Fallon / Julian Tang / Veena Raviprakash / Sharon Campbell / Nicola Sheriff / Victoria Blakey / Lesley-Anne Williams / Matthew W Loose / Nadine Holmes / Christopher Moore / Matthew Carlile / Victoria Wright / Fei Sang / Johnny Debebe / Francesc Coll / Adrian W Signell / Gilberto Betancor / Harry D Wilson / Sahar Eldirdiri / Anita Kenyon / Thomas Davis / Oliver G Pybus / Louis du Plessis / Alex E Zarebski / Jayna Raghwani / Moritz UG Kraemer / Sarah Francois / Stephen W Attwood / Tetyana I Vasylyeva / Marina Escalera Zamudio / Bernardo Gutierrez / M. Estee Torok / William L Hamilton / Ian G Goodfellow / Grant Hall / Aminu S Jahun / Yasmin Chaudhry / Myra Hosmillo / Malte L Pinckert / Iliana Georgana / Samuel Moses / Hannah Lowe / Luke Bedford / Jonathan Moore / Susanne Stonehouse / Chloe L Fisher / Ali R Awan / John BoYes / Judith Breuer / Kathryn Ann Harris / Julianne Rose Brown / Divya Shah / Laura Atkinson / Jack CD Lee / Nathaniel Storey / Flavia Flaviani / Adela Alcolea-Medina / Rebecca Williams / Gabrielle Vernet / Michael R Chapman / Lisa J Levett / Judith Heaney / Wendy Chatterton / Monika Pusok / Li Xu-McCrae / Darren L Smith / Matthew Bashton / Gregory R Young / Alison Holmes / Paul Anthony Randell / Alison Cox / Pinglawathee Madona / Frances Bolt / James Price / Siddharth Mookerjee / Manon Ragonnet-Cronin / Fabricia F. Nascimento / David Jorgensen / Igor Siveroni / Rob Johnson / Olivia Boyd / Lily Geidelberg / Erik M Volz / Aileen Rowan / Graham P Taylor / Katherine L Smollett / Nicholas J Loman / Joshua Quick / Claire McMurray / Joanne Stockton / Sam Nicholls / Will Rowe / Radoslaw Poplawski / Alan McNally / Rocio T Martinez Nunez / Jenifer Mason / Trevor I Robinson / Elaine O'Toole / Joanne Watts / Cassie Breen / Angela Cowell / Graciela Sluga / Nicholas W Machin / Shazaad S Y Ahmad / Ryan P George / Fenella Halstead / Venkat Sivaprakasam / Wendy Hogsden / Chris J Illingworth / Chris Jackson / Emma C Thomson / James G Shepherd / Patawee Asamaphan / Marc O Niebel / Kathy K Li / Rajiv N Shah / Natasha G Jesudason / Lily Tong / Alice Broos / Daniel Mair / Jenna Nichols / Stephen N Carmichael / Kyriaki Nomikou / Elihu Aranday-Cortes / Natasha Johnson / Igor Starinskij / Ana da Silva Filipe / David L Robertson / Richard J Orton / Joseph Hughes / Sreenu Vattipally / Joshua B Singer / Seema Nickbakhsh / Antony D Hale / Louissa R Macfarlane-Smith / Katherine L Harper / Holli Carden / Yusri Taha / Brendan AI Payne / Shirelle Burton-Fanning / Sheila Waugh / Jennifer Collins / Gary Eltringham / Steven Rushton / Sarah O'Brien / Amanda Bradley / Alasdair Maclean / Guy Mollett / Rachel Blacow / Kate E Templeton / Martin P McHugh / Rebecca Dewar / Elizabeth Wastenge / Samir Dervisevic / Rachael Stanley / Emma J Meader / Lindsay Coupland / Louise Smith / Clive Graham / Edward Barton / Debra Padgett / Garren Scott / Emma Swindells / Jane Greenaway / Andrew Nelson / Clare M McCann / Wen C Yew / Monique Andersson / Timothy Peto / Anita Justice / David Eyre / Derrick Crook / Tim J Sloan / Nichola Duckworth / Sarah Walsh / Anoop J Chauhan / Sharon Glaysher / Kelly Bicknell / Sarah Wyllie / Scott Elliott / Allyson Lloyd / Robert Impey / Nick Levene / Lynn Monaghan / Declan T Bradley / Tim Wyatt / Elias Allara / Clare Pearson / Husam Osman / Andrew Bosworth / Esther Robinson / Peter Muir / Ian B Vipond / Richard Hopes / Hannah M Pymont / Stephanie Hutchings / Martin D Curran / Surendra Parmar / Angie Lackenby / Tamyo Mbisa / Steven Platt / Shahjahan Miah / David Bibby / Carmen Manso / Jonathan Hubb / Meera Chand / Gavin Dabrera / Mary Ramsay / Daniel Bradshaw / Alicia Thornton / Richard Myers / Ulf Schaefer / Natalie Groves / Eileen Gallagher / David Lee / David Williams / Nicholas Ellaby / Ian Harrison / Hassan Hartman / Nikos Manesis / Vineet Patel / Chloe Bishop / Vicki Chalker / Juan Ledesma / Katherine A Twohig / Matthew T.G. Holden / Sharif Shaaban / Alec Birchley / Alexander Adams / Alisha Davies / Amy Gaskin / Amy Plimmer / Bree Gatica-Wilcox / Caoimhe McKerr / Catherine Moore / Chris Williams / David Heyburn / Elen De Lacy / Ember Hilvers / Fatima Downing / Giri Shankar / Hannah Jones / Hibo Asad / Jason Coombes / Joanne Watkins / Johnathan M Evans / Laia Fina / Laura Gifford / Lauren Gilbert / Lee Graham / Malorie Perry / Mari Morgan / Matthew Bull / Michelle Cronin / Nicole Pacchiarini / Noel Craine / Rachel Jones / Robin Howe / Sally Corden / Sara Rey / Sara Kumziene-SummerhaYes / Sarah Taylor / Simon Cottrell / Sophie Jones / Sue Edwards / Justin O'Grady / Andrew J Page / Alison E Mather / David J Baker / Steven Rudder / Alp Aydin / Gemma L Kay / Alexander J Trotter / Nabil-Fareed Alikhan / Leonardo de Oliveira Martins / Thanh Le-Viet / Lizzie Meadows / Anna Casey / Liz Ratcliffe / David A Simpson / Zoltan Molnar / Thomas Thompson / Erwan Acheson / Jane AH Masoli / Bridget A Knight / Sian Ellard / Cressida Auckland / Christopher R Jones / Tabitha W Mahungu / Dianne Irish-Tavares / Tanzina Haque / Jennifer Hart / Eric Witele / Melisa Louise Fenton / Ashok Dadrah / Amanda Symmonds / Tranprit Saluja / Yann Bourgeois / Garry P Scarlett / Katie F Loveson / Salman Goudarzi / Christopher Fearn / Kate Cook / Hannah Dent / Hannah Paul / David G Partridge / Mohammad Raza / Cariad Evans / Kate Johnson / Steven Liggett / Paul Baker / Stephen Bonner / Sarah Essex / Ronan A Lyons / Kordo Saeed / Adhyana I.K Mahanama / Buddhini Samaraweera / Siona Silveira / Emanuela Pelosi / Eleri Wilson-Davies / Rachel J Williams / Mark Kristiansen / Sunando Roy / Charlotte A Williams / Marius Cotic / Nadua Bayzid / Adam P Westhorpe / John A Hartley / Riaz Jannoo / Helen L Lowe / Angeliki Karamani / Leah Ensell / Jacqui A Prieto / Sarah Jeremiah / Dimitris Grammatopoulos / Sarojini Pandey / Lisa Berry / Katie Jones / Alex Richter / Andrew Beggs / Angus Best / Benita Percival / Jeremy Mirza / Oliver Megram / Megan Mayhew / Liam Crawford / Fiona Ashcroft / Emma Moles-Garcia / Nicola Cumley / Colin P Smith / Giselda Bucca / Andrew R Hesketh / Beth Blane / Sophia T Girgis / Danielle Leek / Sushmita Sridhar / Sally Forrest / Claire Cormie / Harmeet K Gill / Joana Dias / Ellen E Higginson / Mailis Maes / Jamie Young / Leanne M Kermack / Ravi Kumar Gupta / Catherine Ludden / Sharon J Peacock / Sophie Palmer / Carol M Churcher / Nazreen F Hadjirin / Alessandro M Carabelli / Ellena Brooks / Kim S Smith / Katerina Galai / Georgina M McManus / Chris Ruis / Rose K Davidson / Andrew Rambaut / Thomas Williams / Carlos E Balcazar / Michael D Gallagher / Áine O'Toole / Stefan Rooke / Verity Hill / Kathleen A Williamson / Thomas D Stanton / Stephen L Michell / Claire M Bewshea / Ben Temperton / Michelle L Michelsen / Joanna Warwick-Dugdale / Robin Manley / Audrey Farbos / James W Harrison / Christine M Sambles / David J Studholme / Aaron R Jeffries / Alistair C Darby / Julian A Hiscox / Steve Paterson / Miren Iturriza-Gomara / Kathryn A Jackson / Anita O Lucaci / Edith E Vamos / Margaret Hughes / Lucille Rainbow / Richard Eccles / Charlotte Nelson / Mark Whitehead / Lance Turtle / Sam T Haldenby / Richard Gregory / Matthew Gemmell / Claudia Wierzbicki / Hermione J Webster / Thushan I de Silva / Nikki Smith / Adrienn Angyal / Benjamin B Lindsey / Danielle C Groves / Luke R Green / Dennis Wang / Timothy M Freeman / Matthew D Parker / Alexander J Keeley / Paul J Parsons / Rachel M Tucker / Rebecca Brown / Matthew Wyles / Max Whiteley / Peijun Zhang / Marta Gallis / Stavroula F Louka / Chrystala Constantinidou / Meera Unnikrishnan / Sascha Ott / Jeffrey K.J. Cheng / Hannah E. Bridgewater / Lucy R. Frost / Grace Taylor-Joyce / Richard Stark / Laura Baxter / Mohammad T. Alam / Paul E Brown / Dinesh Aggarwal / Alberto C Cerda / Tammy V Merrill / Rebekah E Wilson / Patrick C McClure / Joseph G Chappell / Theocharis Tsoleridis / Jonathan Ball / David Buck / John A Todd / Angie Green / Amy Trebes / George MacIntyre-Cockett / Mariateresa de Cesare / Alex Alderton / Roberto Amato / Cristina V Ariani / Mathew A Beale / Charlotte Beaver / Katherine L Bellis / Emma Betteridge / James Bonfield / John Danesh / Matthew J Dorman / Eleanor Drury / Ben W Farr / Luke Foulser / Sonia Goncalves / Scott Goodwin / Marina Gourtovaia / Ewan M Harrison / David K Jackson / Dorota Jamrozy / Ian Johnston / Leanne Kane / Sally Kay / Jon-Paul Keatley / Dominic Kwiatkowski / Cordelia F Langford / Mara Lawniczak / Laura Letchford / Rich Livett / Stephanie Lo / Inigo Martincorena / Samantha McGuigan / Rachel Nelson / Steve Palmer / Naomi R Park / Minal Patel / Liam Prestwood / Christoph Puethe / Michael A Quail / Shavanthi Rajatileka / Carol Scott / Lesley Shirley / John Sillitoe / Michael H Spencer Chapman / Scott AJ Thurston / Gerry Tonkin-Hill / Danni Weldon / Diana Rajan / Iraad F Bronner / Louise Aigrain / Nicholas M Redshaw / Stefanie V Lensing / Robert Davies / Andrew Whitwham / Jennifier Liddle / Kevin Lewis / Jaime M Tovar-Corona / Steven Leonard / Jillian Durham / Andrew R Bassett / Shane McCarthy / Robin J Moll / Keith James / Karen Oliver / Alex Makunin / Jeff Barrett / Rory N Gunson

The Lancet Public Health, Vol 6, Iss 5, Pp e335-e

an ecological study

2021 Volume 345

Abstract: Summary: 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 ... ...

Abstract	Summary: 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 reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
Keywords	Public aspects of medicine ; RA1-1270
Subject code	150
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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