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  1. AU="Hassan Hartman"
  2. AU="Song, Mengwei"
  3. AU="Yimin Geng"
  4. AU="Wang, Chang-Sheng"
  5. AU="Doyle, Andrew D"
  6. AU="Redpath, Sophie H A"
  7. AU="Hopman, Maria Te"
  8. AU="Pomputius, William"
  9. AU="Agrawal, Sonali"
  10. AU="Martinez, Luis R"
  11. AU="Passoni, Lorena"
  12. AU="Slimani, Wafa"
  13. AU="Jin, J"
  14. AU="Xia, Hongmin"
  15. AU="Akdemir, İrem"
  16. AU=Ciccone Giovannino

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  1. Artikel ; Online: Surveillance and Stewardship Approaches for COVID-19 Novel Therapeutics in England from 2021 to 2022 (ESPAUR Report)

    Alessandra Løchen / Hanna Squire / Diane Ashiru-Oredope / Kieran S. Hand / Hassan Hartman / Carry Triggs-Hodge / Holly Fountain / Sabine Bou-Antoun / Alicia Demirjian / Sarah M. Gerver

    Medical Sciences Forum, Vol 15, Iss 1, p

    2023  Band 2

    Abstract: The UK Health Security Agency’s (UKHSA) COVID-19 therapeutics programme was commissioned by the Department of Health and Social Care with the remit to evaluate the use and role of COVID-19 treatments. COVID-19 therapeutics data were assessed from two ... ...

    Abstract The UK Health Security Agency’s (UKHSA) COVID-19 therapeutics programme was commissioned by the Department of Health and Social Care with the remit to evaluate the use and role of COVID-19 treatments. COVID-19 therapeutics data were assessed from two main data sources: novel therapy requests via Blueteq and medicines supply data via Rx-info. The five COVID-19 therapies in use in England between 1 October 2021 and 31 March 2022 included nirmatrelvir plus ritonavir, remdesivir, molnupiravir, sotrovimab, and casirivimab with imdevimab. During this time period, treatment requests for novel therapies against COVID-19 were submitted for nearly 52,000 patients in England. The UKHSAs COVID-19 therapeutics programme has been key to supporting the deployment of novel COVID-19 therapies in England by undertaking genomic, virological, and epidemiologic surveillance, through both national surveillance systems and academic collaboration. Effective therapies are particularly important for protecting the health of patients at greater risk of developing severe COVID-19. This national surveillance and stewardship programme was successfully rolled out at pace at the start of the pandemic and leads on work nationally to reduce the development of resistance. These findings were presented at the ESPAUR Report webinar on 23 November 2022.
    Schlagwörter COVID-19 novel therapeutics ; neutralising monoclonal antibodies ; antivirals ; COVID-19 ; antimicrobial stewardship ; Medicine ; R
    Thema/Rubrik (Code) 360
    Sprache Englisch
    Erscheinungsdatum 2023-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: A genome-scale metabolic model of Cupriavidus necator H16 integrated with TraDIS and transcriptomic data reveals metabolic insights for biotechnological applications.

    Nicole Pearcy / Marco Garavaglia / Thomas Millat / James P Gilbert / Yoseb Song / Hassan Hartman / Craig Woods / Claudio Tomi-Andrino / Rajesh Reddy Bommareddy / Byung-Kwan Cho / David A Fell / Mark Poolman / John R King / Klaus Winzer / Jamie Twycross / Nigel P Minton

    PLoS Computational Biology, Vol 18, Iss 5, p e

    2022  Band 1010106

    Abstract: Exploiting biological processes to recycle renewable carbon into high value platform chemicals provides a sustainable and greener alternative to current reliance on petrochemicals. In this regard Cupriavidus necator H16 represents a particularly ... ...

    Abstract Exploiting biological processes to recycle renewable carbon into high value platform chemicals provides a sustainable and greener alternative to current reliance on petrochemicals. In this regard Cupriavidus necator H16 represents a particularly promising microbial chassis due to its ability to grow on a wide range of low-cost feedstocks, including the waste gas carbon dioxide, whilst also naturally producing large quantities of polyhydroxybutyrate (PHB) during nutrient-limited conditions. Understanding the complex metabolic behaviour of this bacterium is a prerequisite for the design of successful engineering strategies for optimising product yields. We present a genome-scale metabolic model (GSM) of C. necator H16 (denoted iCN1361), which is directly constructed from the BioCyc database to improve the readability and reusability of the model. After the initial automated construction, we have performed extensive curation and both theoretical and experimental validation. By carrying out a genome-wide essentiality screening using a Transposon-directed Insertion site Sequencing (TraDIS) approach, we showed that the model could predict gene knockout phenotypes with a high level of accuracy. Importantly, we indicate how experimental and computational predictions can be used to improve model structure and, thus, model accuracy as well as to evaluate potential false positives identified in the experiments. Finally, by integrating transcriptomics data with iCN1361 we create a condition-specific model, which, importantly, better reflects PHB production in C. necator H16. Observed changes in the omics data and in-silico-estimated alterations in fluxes were then used to predict the regulatory control of key cellular processes. The results presented demonstrate that iCN1361 is a valuable tool for unravelling the system-level metabolic behaviour of C. necator H16 and can provide useful insights for designing metabolic engineering strategies.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 670
    Sprache Englisch
    Erscheinungsdatum 2022-05-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

    Manon Ragonnet-Cronin / Rungtiwa Nutalai / Jiandong Huo / Aiste Dijokaite-Guraliuc / Raksha Das / Aekkachai Tuekprakhon / Piyada Supasa / Chang Liu / Muneeswaran Selvaraj / Natalie Groves / Hassan Hartman / Nicholas Ellaby / J. Mark Sutton / Mohammad W. Bahar / Daming Zhou / Elizabeth Fry / Jingshan Ren / Colin Brown / Paul Klenerman /
    Susanna J. Dunachie / Juthathip Mongkolsapaya / Susan Hopkins / Meera Chand / David I. Stuart / Gavin R. Screaton / Sakib Rokadiya

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

    2023  Band 12

    Abstract: Abstract COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies ... ...

    Abstract Abstract COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.
    Schlagwörter Science ; Q
    Thema/Rubrik (Code) 616 ; 570
    Sprache Englisch
    Erscheinungsdatum 2023-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Informal genomic surveillance of regional distribution of Salmonella Typhi genotypes and antimicrobial resistance via returning travellers.

    Danielle J Ingle / Satheesh Nair / Hassan Hartman / Philip M Ashton / Zoe A Dyson / Martin Day / Joanne Freedman / Marie A Chattaway / Kathryn E Holt / Timothy J Dallman

    PLoS Neglected Tropical Diseases, Vol 13, Iss 9, p e

    2019  Band 0007620

    Abstract: Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occurs disproportionately among children in low and middle income countries. ... ...

    Abstract Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occurs disproportionately among children in low and middle income countries. Antimicrobial therapy is the mainstay for treatment, but resistance to multiple agents is common. Here we report genotypes and antimicrobial resistance (AMR) determinants detected from routine whole-genome sequencing (WGS) of 533 S. Typhi isolates referred to Public Health England between April 2014 and March 2017, 488 (92%) of which had accompanying patient travel information obtained via an enhanced surveillance questionnaire. The majority of cases involved S. Typhi 4.3.1 (H58) linked with travel to South Asia (59%). Travel to East and West Africa were associated with genotypes 4.3.1 and 3.3.1, respectively. Point mutations in the quinolone resistance determining region (QRDR), associated with reduced susceptibility to fluoroquinolones, were very common (85% of all cases) but the frequency varied significantly by region of travel: 95% in South Asia, 43% in East Africa, 27% in West Africa. QRDR triple mutants, resistant to ciprofloxacin, were restricted to 4.3.1 lineage II and associated with travel to India, accounting for 23% of cases reporting travel to the country. Overall 24% of isolates were MDR, however the frequency varied significantly by region and country of travel: 27% in West Africa, 52% in East Africa, 55% in Pakistan, 24% in Bangladesh, 3% in India. MDR determinants were plasmid-borne (IncHI1 PST2 plasmids) in S. Typhi 3.1.1 linked to West Africa, but in all other regions MDR was chromosomally integrated in 4.3.1 lineage I. We propose that routine WGS data from travel-associated cases in industrialised countries could serve as informal sentinel AMR genomic surveillance data for countries where WGS is not available or routinely performed.
    Schlagwörter Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Thema/Rubrik (Code) 390
    Sprache Englisch
    Erscheinungsdatum 2019-09-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: The Transformation of Reference Microbiology Methods and Surveillance for Salmonella With the Use of Whole Genome Sequencing in England and Wales

    Marie Anne Chattaway / Timothy J. Dallman / Lesley Larkin / Satheesh Nair / Jacquelyn McCormick / Amy Mikhail / Hassan Hartman / Gauri Godbole / David Powell / Martin Day / Robert Smith / Kathie Grant

    Frontiers in Public Health, Vol

    2019  Band 7

    Abstract: The use of whole genome sequencing (WGS) as a method for supporting outbreak investigations, studying Salmonella microbial populations and improving understanding of pathogenicity has been well-described (1–3). However, performing WGS on a discrete ... ...

    Abstract The use of whole genome sequencing (WGS) as a method for supporting outbreak investigations, studying Salmonella microbial populations and improving understanding of pathogenicity has been well-described (1–3). However, performing WGS on a discrete dataset does not pose the same challenges as implementing WGS as a routine, reference microbiology service for public health surveillance. Challenges include translating WGS data into a useable format for laboratory reporting, clinical case management, Salmonella surveillance, and outbreak investigation as well as meeting the requirement to communicate that information in an understandable and universal language for clinical and public health action. Public Health England have been routinely sequencing all referred presumptive Salmonella isolates since 2014 which has transformed our approach to reference microbiology and surveillance. Here we describe an overview of the integrated methods for cross-disciplinary working, describe the challenges and provide a perspective on how WGS has impacted the laboratory and surveillance processes in England and Wales.
    Schlagwörter WGS ; genomic typing ; molecular epidemiology ; Salmonella ; SNP typing ; Public aspects of medicine ; RA1-1270
    Thema/Rubrik (Code) 306
    Sprache Englisch
    Erscheinungsdatum 2019-11-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Emergence of phylogenetically diverse and fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal Salmonella disease in Ghana.

    Cassandra Aldrich / Hassan Hartman / Nicholas Feasey / Marie Anne Chattaway / Denise Dekker / Hassan M Al-Emran / Lesley Larkin / Jacquelyn McCormick / Nimako Sarpong / Simon Le Hello / Yaw Adu-Sarkodie / Ursula Panzner / Se Eun Park / Justin Im / Florian Marks / Jürgen May / Timothy J Dallman / Daniel Eibach

    PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e

    2019  Band 0007485

    Abstract: Background Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes ...

    Abstract Background Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages. Methodology/principal findings Twenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region. Conclusions/significance Extensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures ...
    Schlagwörter Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2019-06-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Identification of metabolic pathways essential for fitness of Salmonella Typhimurium in vivo.

    Lotte Jelsbak / Hassan Hartman / Casper Schroll / Jesper T Rosenkrantz / Sebastien Lemire / Inke Wallrodt / Line E Thomsen / Mark Poolman / Mogens Kilstrup / Peter R Jensen / John E Olsen

    PLoS ONE, Vol 9, Iss 7, p e

    2014  Band 101869

    Abstract: Bacterial infections remain a threat to human and animal health worldwide, and there is an urgent need to find novel targets for intervention. In the current study we used a computer model of the metabolic network of Salmonella enterica serovar ... ...

    Abstract Bacterial infections remain a threat to human and animal health worldwide, and there is an urgent need to find novel targets for intervention. In the current study we used a computer model of the metabolic network of Salmonella enterica serovar Typhimurium and identified pairs of reactions (cut sets) predicted to be required for growth in vivo. We termed such cut sets synthetic auxotrophic pairs. We tested whether these would reveal possible combined targets for new antibiotics by analyzing the performance of selected single and double mutants in systemic mouse infections. One hundred and two cut sets were identified. Sixty-three of these included only pathways encoded by fully annotated genes, and from this sub-set we selected five cut sets involved in amino acid or polyamine biosynthesis. One cut set (asnA/asnB) demonstrated redundancy in vitro and in vivo and showed that asparagine is essential for S. Typhimurium during infection. trpB/trpA as well as single mutants were attenuated for growth in vitro, while only the double mutant was a cut set in vivo, underlining previous observations that tryptophan is essential for successful outcome of infection. speB/speF,speC was not affected in vitro but was attenuated during infection showing that polyamines are essential for virulence apparently in a growth independent manner. The serA/glyA cut-set was found to be growth attenuated as predicted by the model. However, not only the double mutant, but also the glyA mutant, were found to be attenuated for virulence. This adds glycine production or conversion of glycine to THF to the list of essential reactions during infection. One pair (thrC/kbl) showed true redundancy in vitro but not in vivo demonstrating that threonine is available to the bacterium during infection. These data add to the existing knowledge of available nutrients in the intra-host environment, and have identified possible new targets for antibiotics.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; 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. 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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  Band 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.
    Schlagwörter Public aspects of medicine ; RA1-1270
    Thema/Rubrik (Code) 150
    Sprache Englisch
    Erscheinungsdatum 2021-05-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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