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  1. Article ; Online: Modification of Bacteriophages to Increase Their Association with Lung Epithelium Cells In Vitro

    Aurelija M. Grigonyte / Alexia Hapeshi / Chrystala Constantinidou / Andrew Millard

    Pharmaceuticals, Vol 14, Iss 308, p

    2021  Volume 308

    Abstract: There is currently a renaissance in research on bacteriophages as alternatives to antibiotics. Phage specificity to their bacterial host, in addition to a plethora of other advantages, makes them ideal candidates for a broad range of applications, ... ...

    Abstract There is currently a renaissance in research on bacteriophages as alternatives to antibiotics. Phage specificity to their bacterial host, in addition to a plethora of other advantages, makes them ideal candidates for a broad range of applications, including bacterial detection, drug delivery, and phage therapy in particular. One issue obstructing phage efficiency in phage therapy settings is their poor localization to the site of infection in the human body. Here, we engineered phage T7 with lung tissue targeting homing peptides. We then used in vitro studies to demonstrate that the engineered T7 phages had a more significant association with the lung epithelium cells than wild-type T7. In addition, we showed that, in general, there was a trend of increased association of engineered phages with the lung epithelium cells but not mouse fibroblast cells, allowing for targeted tissue specificity. These results indicate that appending phages with homing peptides would potentially allow for greater phage concentrations and greater efficacy at the infection site.
    Keywords phage therapy ; bacteriophage T7 ; marker-based engineering ; homing peptide ; synthetic biology ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 610 ; 500
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Lineage skewing and genome instability underlie marrow failure in a zebrafish model of GATA2 deficiency

    Christopher B. Mahony / Lucy Copper / Pavle Vrljicak / Boris Noyvert / Chrystala Constantinidou / Sofia Browne / Yi Pan / Claire Palles / Sascha Ott / Martin R. Higgs / Rui Monteiro

    Cell Reports, Vol 42, Iss 6, Pp 112571- (2023)

    2023  

    Abstract: Summary: Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes toward hematological malignancies, but the mechanisms remain poorly understood. Here, we investigate the mechanistic basis of marrow failure in a zebrafish ...

    Abstract Summary: Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes toward hematological malignancies, but the mechanisms remain poorly understood. Here, we investigate the mechanistic basis of marrow failure in a zebrafish model of GATA2 deficiency. Single-cell transcriptomics and chromatin accessibility assays reveal that loss of gata2a leads to skewing toward the erythroid lineage at the expense of myeloid cells, associated with loss of cebpa expression and decreased PU.1 and CEBPA transcription factor accessibility in hematopoietic stem and progenitor cells (HSPCs). Furthermore, gata2a mutants show impaired expression of npm1a, the zebrafish NPM1 ortholog. Progressive loss of npm1a in HSPCs is associated with elevated levels of DNA damage in gata2a mutants. Thus, Gata2a maintains myeloid lineage priming through cebpa and protects against genome instability and marrow failure by maintaining expression of npm1a. Our results establish a potential mechanism underlying bone marrow failure in GATA2 deficiency.
    Keywords CP: Molecular biology ; CP: Stem cell research ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: The Enigmatic Esx Proteins: Looking Beyond Mycobacteria

    Unnikrishnan, Meera / Chrystala Constantinidou / Mark J. Pallen / Tracy Palmer

    Trends in microbiology. 2017 Mar., v. 25, no. 3

    2017  

    Abstract: Bacteria export proteins across membranes using a range of transport machineries. Type VII secretion systems (T7SSs), originally described in mycobacteria, are now known to be widespread across diverse bacterial phyla. Recent studies have characterized ... ...

    Abstract Bacteria export proteins across membranes using a range of transport machineries. Type VII secretion systems (T7SSs), originally described in mycobacteria, are now known to be widespread across diverse bacterial phyla. Recent studies have characterized secretion components and mechanisms of type VII secretion in pathogenic and environmental bacteria. A variety of functions have been attributed to T7SS substrates, including interactions with eukaryotes and with other bacteria. Here, we evaluate the growing body of knowledge on T7SSs, with focus on the nonmycobacterial systems, reviewing their phylogenetic distribution, structure and function in diverse settings.
    Keywords bacteria ; eukaryotic cells ; phylogeny ; protein transport ; proteins ; secretion
    Language English
    Dates of publication 2017-03
    Size p. 192-204.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1158963-2
    ISSN 1878-4380 ; 0966-842X
    ISSN (online) 1878-4380
    ISSN 0966-842X
    DOI 10.1016/j.tim.2016.11.004
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: High-throughput sequencing of 16S rRNA gene amplicons

    Martin J Sergeant / Chrystala Constantinidou / Tristan Cogan / Charles W Penn / Mark J Pallen

    PLoS ONE, Vol 7, Iss 5, p e

    effects of extraction procedure, primer length and annealing temperature.

    2012  Volume 38094

    Abstract: The analysis of 16S-rDNA sequences to assess the bacterial community composition of a sample is a widely used technique that has increased with the advent of high throughput sequencing. Although considerable effort has been devoted to identifying the ... ...

    Abstract The analysis of 16S-rDNA sequences to assess the bacterial community composition of a sample is a widely used technique that has increased with the advent of high throughput sequencing. Although considerable effort has been devoted to identifying the most informative region of the 16S gene and the optimal informatics procedures to process the data, little attention has been paid to the PCR step, in particular annealing temperature and primer length. To address this, amplicons derived from 16S-rDNA were generated from chicken caecal content DNA using different annealing temperatures, primers and different DNA extraction procedures. The amplicons were pyrosequenced to determine the optimal protocols for capture of maximum bacterial diversity from a chicken caecal sample. Even at very low annealing temperatures there was little effect on the community structure, although the abundance of some OTUs such as Bifidobacterium increased. Using shorter primers did not reveal any novel OTUs but did change the community profile obtained. Mechanical disruption of the sample by bead beating had a significant effect on the results obtained, as did repeated freezing and thawing. In conclusion, existing primers and standard annealing temperatures captured as much diversity as lower annealing temperatures and shorter primers.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Extensive microbial and functional diversity within the chicken cecal microbiome.

    Martin J Sergeant / Chrystala Constantinidou / Tristan A Cogan / Michael R Bedford / Charles W Penn / Mark J Pallen

    PLoS ONE, Vol 9, Iss 3, p e

    2014  Volume 91941

    Abstract: Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, including the ceca. We have carried out deep microbial ... ...

    Abstract Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, including the ceca. We have carried out deep microbial community profiling of the microbiota in twenty cecal samples via 16S rRNA gene sequences and an in-depth metagenomics analysis of a single cecal microbiota. We recovered 699 phylotypes, over half of which appear to represent previously unknown species. We obtained 648,251 environmental gene tags (EGTs), the majority of which represent new species. These were binned into over two-dozen draft genomes, which included Campylobacter jejuni and Helicobacter pullorum. We found numerous polysaccharide- and oligosaccharide-degrading enzymes encoding within the metagenome, some of which appeared to be part of polysaccharide utilization systems with genetic evidence for the co-ordination of polysaccharide degradation with sugar transport and utilization. The cecal metagenome encodes several fermentation pathways leading to the production of short-chain fatty acids, including some with novel features. We found a dozen uptake hydrogenases encoded in the metagenome and speculate that these provide major hydrogen sinks within this microbial community and might explain the high abundance of several genera within this microbiome, including Campylobacter, Helicobacter and Megamonas.
    Keywords Medicine ; R ; Science ; Q
    Subject code 590
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Microarray analysis of the Ler regulon in enteropathogenic and enterohaemorrhagic Escherichia coli strains.

    Lewis E H Bingle / Chrystala Constantinidou / Robert K Shaw / Md Shahidul Islam / Mala Patel / Lori A S Snyder / David J Lee / Charles W Penn / Stephen J W Busby / Mark J Pallen

    PLoS ONE, Vol 9, Iss 1, p e

    2014  Volume 80160

    Abstract: The type III protein secretion system is an important pathogenicity factor of enteropathogenic and enterohaemorrhagic Escherichia coli pathotypes. The genes encoding this apparatus are located on a pathogenicity island (the locus of enterocyte effacement) ...

    Abstract The type III protein secretion system is an important pathogenicity factor of enteropathogenic and enterohaemorrhagic Escherichia coli pathotypes. The genes encoding this apparatus are located on a pathogenicity island (the locus of enterocyte effacement) and are transcriptionally activated by the master regulator Ler. In each pathotype Ler is also known to regulate genes located elsewhere on the chromosome, but the full extent of the Ler regulon is unclear, especially for enteropathogenic E. coli. The Ler regulon was defined for two strains of E. coli: E2348/69 (enteropathogenic) and EDL933 (enterohaemorrhagic) in mid and late log phases of growth by DNA microarray analysis of the transcriptomes of wild-type and ler mutant versions of each strain. In both strains the Ler regulon is focused on the locus of enterocyte effacement - all major transcriptional units of which are activated by Ler, with the sole exception of the LEE1 operon during mid-log phase growth in E2348/69. However, the Ler regulon does extend more widely and also includes unlinked pathogenicity genes: in E2348/69 more than 50 genes outside of this locus were regulated, including a number of known or potential pathogenicity determinants; in EDL933 only 4 extra-LEE genes, again including known pathogenicity factors, were activated. In E2348/69, where the Ler regulon is clearly growth phase dependent, a number of genes including the plasmid-encoded regulator operon perABC, were found to be negatively regulated by Ler. Negative regulation by Ler of PerC, itself a positive regulator of the ler promoter, suggests a negative feedback loop involving these proteins.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine.

    Nicholas J Loman / Rebecca A Gladstone / Chrystala Constantinidou / Anna S Tocheva / Johanna M C Jefferies / Saul N Faust / Leigh O'Connor / Jacqueline Chan / Mark J Pallen / Stuart C Clarke

    PLoS ONE, Vol 8, Iss 5, p e

    2013  Volume 64731

    Abstract: Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a ... ...

    Abstract Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB.

    Katherine A Abrahams / Jonathan A G Cox / Vickey L Spivey / Nicholas J Loman / Mark J Pallen / Chrystala Constantinidou / Raquel Fernández / Carlos Alemparte / Modesto J Remuiñán / David Barros / Lluis Ballell / Gurdyal S Besra

    PLoS ONE, Vol 7, Iss 12, p e

    2012  Volume 52951

    Abstract: Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. ... ...

    Abstract Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. Through the use of high throughput whole cell screening of an extensive compound library a number of imidazo[1,2-a]pyridine (IP) compounds were obtained as potent lead molecules active against M. tuberculosis and Mycobacterium bovis BCG. The IP inhibitors (1-4) demonstrated minimum inhibitory concentrations (MICs) in the range of 0.03 to 5 µM against a panel of M. tuberculosis strains. M. bovis BCG spontaneous resistant mutants were generated against IP 1, 3, and 4 at 5× MIC and subsequent whole genome sequencing identified a single nucleotide polymorphism (937)ACC>(937)GCC (T313A) in qcrB, which encodes the b subunit of the electron transport ubiquinol cytochrome C reductase. This mutation also conferred cross-resistance against IP 1, 3 and 4 demonstrating a common target. Gene dosage experiments confirmed M. bovis BCG QcrB as the target where over-expression in M. bovis BCG led to an increase in MIC from 0.5 to >8 µM for IP 3. An acute murine model of TB infection established bacteriostatic activity of the IP series, which await further detailed characterization.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3.

    Modesto J Remuiñán / Esther Pérez-Herrán / Joaquín Rullás / Carlos Alemparte / María Martínez-Hoyos / David J Dow / Johnson Afari / Nalini Mehta / Jorge Esquivias / Elena Jiménez / Fátima Ortega-Muro / María Teresa Fraile-Gabaldón / Vickey L Spivey / Nicholas J Loman / Mark J Pallen / Chrystala Constantinidou / Douglas J Minick / Mónica Cacho / María José Rebollo-López /
    Carolina González / Verónica Sousa / Iñigo Angulo-Barturen / Alfonso Mendoza-Losana / David Barros / Gurdyal S Besra / Lluís Ballell / Nicholas Cammack

    PLoS ONE, Vol 8, Iss 4, p e

    2013  Volume 60933

    Abstract: Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As ... ...

    Abstract Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This 'genetic phenotype' was further confirmed by a 'chemical phenotype', whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. 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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