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  1. Article ; Online: Mid-regional proadrenomedullin (MR-proADM), C-reactive protein (CRP) and other biomarkers in the early identification of disease progression in patients with COVID-19 in the acute NHS setting.

    Moore, Nathan / Williams, Rebecca / Mori, Matilde / Bertolusso, Beatrice / Vernet, Gabrielle / Lynch, Jessica / Philipson, Pete / Ledgerwood, Thomas / Kidd, Stephen P / Thomas, Claire / Garcia-Arias, Veronica / Young, Michelle / Saeed, Kordo / Gordon, Kirsty / Cortes, Nicholas

    Journal of clinical pathology

    2022  Volume 76, Issue 6, Page(s) 400–406

    Abstract: Aims: There is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), ... ...

    Abstract Aims: There is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), procalcitonin, mid-regional proadrenomedullin (MR-proADM) and white cell count to support prediction of clinical outcomes.
    Methods: 135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via reverse-transcription-qPCR were included. Biomarkers from within 24 hours of presentation were used to predict disease progression by Cox regression and area under the receiver operating characteristic curves. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, critical care admission and non-invasive ventilation (NIV) use.
    Results: Elevated MR-proADM was shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and NIV.
    Conclusions: The measurement of MR-proADM and CRP in patients with confirmed COVID-19 infection on admission shows significant potential to support clinicians in identifying those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions.
    MeSH term(s) Humans ; Adrenomedullin/analysis ; Biomarkers/analysis ; C-Reactive Protein/analysis ; COVID-19/diagnosis ; Disease Progression ; Prognosis
    Chemical Substances Adrenomedullin (148498-78-6) ; Biomarkers ; C-Reactive Protein (9007-41-4) ; proadrenomedullin
    Language English
    Publishing date 2022-01-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 80261-x
    ISSN 1472-4146 ; 0021-9746
    ISSN (online) 1472-4146
    ISSN 0021-9746
    DOI 10.1136/jclinpath-2021-207750
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: C-reactive protein-guided use of procalcitonin in COVID-19.

    Houghton, Rebecca / Moore, Nathan / Williams, Rebecca / El-Bakri, Fatima / Peters, Jonathan / Mori, Matilde / Vernet, Gabrielle / Lynch, Jessica / Lewis, Henry / Tavener, Maryanna / Durham, Tom / Bowyer, Jack / Saeed, Kordo / Pollara, Gabriele

    JAC-antimicrobial resistance

    2021  Volume 3, Issue 4, Page(s) dlab180

    Abstract: Background: A low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein ( ...

    Abstract Background: A low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein (CRP), can be concordant, and predicting low PCT concentrations may avoid costs of redundant tests and support more cost-effective deployment of this diagnostic biomarker.
    Objectives: To explore whether, in COVID-19, low PCT values could be predicted by the presence of low CRP concentrations.
    Methods: Unselected cohort of 224 COVID-19 patients admitted to hospital that underwent daily PCT and CRP measurements as standard care. Both 0.25 ng/mL and 0.5 ng/mL were used as cut-offs for positive PCT test results. Geometric mean was used to define high and low CRP values at each timepoint assessed.
    Results: Admission PCT was <0.25 ng/mL in 160/224 (71.4%), 0.25-0.5 ng/mL in 27 (12.0%) and >0.5 ng/mL in 37 (16.5%). Elevated PCT was associated with increased risk of death (
    Conclusions: CRP-guided PCT testing algorithms can reduce unnecessary PCT measurement and costs, supporting antimicrobial stewardship strategies in COVID-19.
    Language English
    Publishing date 2021-11-28
    Publishing country England
    Document type Journal Article
    ISSN 2632-1823
    ISSN (online) 2632-1823
    DOI 10.1093/jacamr/dlab180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mid-Regional pro-Adrenomedullin (MR-proADM), C-Reactive Protein (CRP) and Other Biomarkers in the Early Identification of Disease Progression in COVID-19 Patients in the Acute NHS Setting

    Moore, Nathan A. / Williams, Rebecca / Mori, Matilde / Bertolusso, Beatrice / Vernet, Gabrielle / Lynch, Jessica / Philipson, Peter / Ledgerwood, Thomas / Kidd, Stephen P. / Thomas, Claire / Garcia-Arias, Veronica / Young, Michelle / Saeed, Kordo / Gordon, Kirsty / Cortes, Nicholas

    medRxiv

    Abstract: Background: There is a lack of biomarkers validated for assessing clinical deterioration in COVID-19 patients upon presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of a range of biomarkers, ... ...

    Abstract Background: There is a lack of biomarkers validated for assessing clinical deterioration in COVID-19 patients upon presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of a range of biomarkers, including C-Reactive Protein (CRP) and Procalcitonin (PCT) and Mid-Regional pro-adrenomedullin (MR-proADM), and White Cell Count to support prediction of clinical outcomes. Methods: Adult patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via RT-qPCR were included. Biomarkers were measured in blood samples taken within 24 hours of admission and logistic regression and area under the receiver operating characteristic (AUROC) curves were used to predict disease progression. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, admission to critical care and non-invasive ventilation (NIV) use. Findings: A total of 135 adult patients were identified. Elevated levels of MR-proADM were shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and non-invasive ventilation, when controlling for covariates. Interpretation: The measurement of biomarkers, particularly MR-proADM and CRP in patients with confirmed COVID-19 infection upon admission to secondary care shows significant potential to support clinicians in the early identification of those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions and treatment.
    Keywords covid19
    Language English
    Publishing date 2021-04-22
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.04.19.21252978
    Database COVID19

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  4. Article ; Online: SARS-CoV-2 within-host diversity and transmission.

    Lythgoe, Katrina A / Hall, Matthew / Ferretti, Luca / de Cesare, Mariateresa / MacIntyre-Cockett, George / Trebes, Amy / Andersson, Monique / Otecko, Newton / Wise, Emma L / Moore, Nathan / Lynch, Jessica / Kidd, Stephen / Cortes, Nicholas / Mori, Matilde / Williams, Rebecca / Vernet, Gabrielle / Justice, Anita / Green, Angie / Nicholls, Samuel M /
    Ansari, M Azim / Abeler-Dörner, Lucie / Moore, Catrin E / Peto, Timothy E A / Eyre, David W / Shaw, Robert / Simmonds, Peter / Buck, David / Todd, John A / Connor, Thomas R / Ashraf, Shirin / da Silva Filipe, Ana / Shepherd, James / Thomson, Emma C / Bonsall, David / Fraser, Christophe / Golubchik, Tanya

    Science (New York, N.Y.)

    2021  Volume 372, Issue 6539

    Abstract: Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant ... ...

    Abstract Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.
    MeSH term(s) COVID-19/immunology ; COVID-19/transmission ; COVID-19/virology ; Coinfection/virology ; Coronavirus Infections/virology ; Coronavirus OC43, Human ; Family Characteristics ; Genetic Variation ; Genome, Viral ; Humans ; Immune Evasion ; Mutation ; Phylogeny ; RNA, Viral/genetics ; RNA-Seq ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Selection, Genetic ; Spike Glycoprotein, Coronavirus/genetics ; United Kingdom ; Viral Load
    Chemical Substances RNA, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-03-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abg0821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Shared SARS-CoV-2 diversity suggests localised transmission of minority variants

    Lythgoe, Katrina A. / Hall, Matthew / Ferretti, Luca / de Cesare, Mariateresa / MacIntyre-Cockett, George / Trebes, Amy / Andersson, Monique / Otecko, Newton / Wise, Emma L. / Moore, Nathan / Lynch, Jessica / Kidd, Stephen / Cortes, Nicholas / Mori, Matilde / Justice, Anita / Green, Angie / Ansari, M. Azim / Abeler-Dörner, Lucie / Moore, Catrin E. /
    Peto, Tim E. A. / Shaw, Robert / Simmonds, Peter / Buck, David / Todd, John A. / Bonsall, David / Fraser, Christophe / Golubchik, Tanya

    bioRxiv

    Abstract: We gratefully acknowledge the UK COVID-19 Genomics Consortium (COG UK) for funding, and Public Health Wales / Cardiff University and MRC-University of Glasgow Centre for Virus Research for making their COG-UK sequence data publicly available. COG-UK is ... ...

    Abstract We gratefully acknowledge the UK COVID-19 Genomics Consortium (COG UK) for funding, and Public Health Wales / Cardiff University and MRC-University of Glasgow Centre for Virus Research for making their COG-UK sequence data publicly available. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. The research was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with funding from the NIHR Oxford BRC. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We are deeply grateful to Robert Esnouf and the BMRC Research Computing team for unfailing assistance with computational infrastructure. We also thank Benjamin Carpenter and James Docker for assistance in the laboratory, and Lorne Lonie, Maria Lopopolo, Chris Allen, John Broxholme and the WHG high-throughput genomics team for sequencing and quality control. The HIV clone p92BR025.8 was obtained through the Centre For AIDS Reagents from Drs Beatrice Hahn and Feng Gao, and the UNAIDS Virus Network (courtesy of the NIH AIDS Research and Reference Reagent Program). KAL is supported by The Wellcome Trust and The Royal Society (107652/Z/15/Z). MH, LF, MdC, GMC, NO, LAD, DB, CF and TG are supported by Li Ka Shing Foundation funding awarded to CF. PS is supported by a Wellcome Investigator Award (WT103767MA). Summary SARS-CoV-2, the causative agent of COVID-19, emerged in late 2019 causing a global pandemic, with the United Kingdom (UK) one of the hardest hit countries. Rapid sequencing and publication of consensus genomes have enabled phylogenetic analysis of the virus, demonstrating SARS-CoV-2 evolves relatively slowly1, but with multiple sites in the genome that appear inconsistent with the overall consensus phylogeny2. To understand these discrepancies, we used veSEQ3, a targeted RNA-seq approach, to quantify minor allele frequencies in 413 clinical samples from two UK locations. We show that SARS-CoV-2 infections are characterised by extensive within-host diversity, which is frequently shared among infected individuals with patterns consistent with geographical structure. These results were reproducible in data from two other sequencing locations in the UK, where we find evidence of mixed infection by major circulating lineages with patterns that cannot readily be explained by artefacts in the data. We conclude that SARS-CoV-2 diversity is transmissible, and propose that geographic patterns are generated by transient co-circulation of distinct viral populations. Co-transmission of mixed populations could open opportunities for resolving clusters of transmission and understanding pathogenesis.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.05.28.118992
    Database COVID19

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  6. Article ; Online: Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

    Volz, Erik / Hill, Verity / McCrone, John T. / Price, Anna / Jorgensen, David / O’Toole, Áine / Southgate, Joel / Johnson, Robert / Jackson, Ben / Nascimento, Fabricia F. / Rey, Sara M. / Nicholls, Samuel M. / Colquhoun, Rachel M. / da Silva Filipe, Ana / Shepherd, James / Pascall, David J. / Shah, Rajiv / Jesudason, Natasha / Li, Kathy /
    Jarrett, Ruth / Pacchiarini, Nicole / Bull, Matthew / Geidelberg, Lily / Siveroni, Igor / Goodfellow, Ian / Loman, Nicholas J. / Pybus, Oliver G. / Robertson, Dave / Thomson, Emma C. / Rambaut, Andrew / Connor, Thomas R. / Koshy, Cherian / Wise, Emma / Cortes, Nick / Lynch, Jessica / Kidd, Stephen / Mori, Matilde / Fairley, Derek J. / Curran, Tanya / McKenna, James P. / Adams, Helen / Fraser, Christophe / Golubchik, Tanya / Bonsall, David / Moore, Catrin / Caddy, Sarah L. / Khokhar, Fahad A. / Wantoch, Michelle / Reynolds, Nicola / Warne, Ben / Maksimovic, Joshua / Spellman, Karla / McCluggage, Kathryn / John, Michaela / Beér, Robert / Afifi, Safiah / Morgan, Siân / Marchbank, Angela / Kitchen, C. / Gulliver, Huw / Merrick, Ian / Guest, Martyn / Munn, Robert / Workman, Trudy / Fuller, William / Bresner, Catherine / Snell, Luke B. / Charalampous, Themoula / Nebbia, Gaia / Batra, Rahul / Edgeworth, Jonathan / Robson, Samuel C. / Beckett, Angela / Loveson, Katie F. / Aanensen, David M. / Underwood, Anthony P. / Yeats, Corin A. / Abudahab, Khalil / Taylor, Ben E.W. / Menegazzo, Mirko / Clark, Gemma / Smith, Wendy / Khakh, Manjinder / Fleming, Vicki M. / Lister, Michelle M. / Howson-Wells, Hannah C. / Berry, Louise / Boswell, Tim / Joseph, Amelia / Willingham, Iona / Bird, Paul / Helmer, Thomas / Fallon, Karlie / Holmes, Christopher / Tang, Julian / Raviprakash, Veena / Campbell, Sharon / Sheriff, Nicola / Loose, Matthew W. / Holmes, Nadine / Moore, Christopher / Carlile, Matthew / Wright, Victoria / Sang, Fei / Debebe, Johnny / Coll, Francesc / Signell, Adrian W. / Betancor, Gilberto / Wilson, Harry D. / Feltwell, Theresa / Houldcroft, Charlotte J. / Eldirdiri, Sahar / Kenyon, Anita / Davis, Thomas / Pybus, Oliver / Du Plessis, L. / Zarebski, Alex / Raghwani, Jayna / Kraemer, Moritz / Francois, Sarah / Attwood, Stephen / Vasylyeva, Tetyana / Török, Estée / Hamilton, William L. / Goodfellow, Ian G. / Hall, Grant / Jahun, Aminu S. / Chaudhry, Yasmin / Hosmillo, Myra / Pinckert, Malte L. / Georgana, Iliana / Yakovleva, Anna / Meredith, Luke W. / Moses, S. / Lowe, Hannah / Ryan, Felicity / Fisher, Chloe L. / Awan, Ali R. / Boyes, John / Breuer, Judith / Harris, Kathryn Ann / Brown, Julianne Rose / Shah, Divya / Atkinson, Laura / Lee, Jack C.D. / Alcolea-Medina, Adela / Moore, Nathan / Cortes, Nicholas / Williams, Rebecca / Chapman, Michael R. / Levett, Lisa J. / Heaney, Judith / Smith, Darren L. / Bashton, Matthew / Young, Gregory R. / Allan, John / Loh, Joshua / Randell, Paul A. / Cox, Ali / Madona, Pinglawathee / Holmes, Alison / Bolt, Frances / Price, James / Mookerjee, Siddharth / Rowan, Aileen / Taylor, Graham P. / Ragonnet-Cronin, Manon / Johnson, Rob / Boyd, Olivia / Volz, Erik M. / Brunker, Kirstyn / Smollett, Katherine L. / Quick, Joshua / McMurray, Claire / Stockton, Joanne / Nicholls, Sam / Rowe, William / Poplawski, Radoslaw / Martinez-Nunez, Rocio T. / Mason, Jenifer / Robinson, Trevor I. / O'Toole, Elaine / Watts, Joanne / Breen, Cassie / Cowell, Angela / Ludden, Catherine / Sluga, Graciela / Machin, Nicholas W. / Ahmad, Shazaad S.Y. / George, Ryan P. / Halstead, Fenella / Sivaprakasam, Venkat / Shepherd, James G. / Asamaphan, Patawee / Niebel, Marc O. / Li, Kathy K. / Shah, Rajiv N. / Jesudason, Natasha G. / Parr, Yasmin A. / Tong, Lily / Broos, Alice / Mair, Daniel / Nichols, Jenna / Carmichael, Stephen N. / Nomikou, Kyriaki / Aranday-Cortes, Elihu / Johnson, NaTasha / Starinskij, Igor / Orton, Richard J. / Hughes, Joseph / Vattipally, Sreenu / Singer, Joshua B. / Hale, Antony D. / Macfarlane-Smith, Louissa R. / Harper, Katherine L. / Taha, Yusri / Payne, Brendan A.I. / Burton-Fanning, Shirelle / Waugh, Sheila / Collins, Jennifer / Eltringham, Gary / Templeton, Kate E. / McHugh, Martin P. / Dewar, Rebecca / Wastenge, Elizabeth / Dervisevic, Samir / Stanley, Rachael / Prakash, Reenesh / Stuart, Claire / Elumogo, Ngozi / Sethi, Dheeraj K. / Meader, Emma J. / Coupland, Lindsay J. / Potter, Will / Graham, Clive / Barton, Edward / Padgett, Debra / Scott, Garren / Swindells, Emma / Greenaway, Jane / Nelson, Andrew / Yew, Wen C. / Resende Silva, Paola C. / Andersson, Monique / Shaw, Robert / Peto, Timothy / Justice, Anita / Eyre, David / Crooke, Derrick / Hoosdally, Sarah / Sloan, Tim J. / Duckworth, Nichola / Walsh, Sarah / Chauhan, Anoop J. / Glaysher, Sharon / Bicknell, Kelly / Wyllie, Sarah / Butcher, Ethan / Elliott, Scott / Lloyd, Allyson / Impey, Robert / Levene, Nick / Monaghan, Lynn / Bradley, Declan T. / Allara, Elias / Pearson, Clare / Muir, Peter / Vipond, Ian B. / Hopes, Richard / Pymont, Hannah M. / Hutchings, Stephanie / Curran, Martin D. / Parmar, Surendra / Lackenby, Angie / Mbisa, Tamyo / Platt, Steven / Miah, Shâhjahân / Bibby, David / Manso, Carmen / Hubb, Jonathan / Chand, Meera / Dabrera, Gavin / Ramsay, Mary / Bradshaw, Daniel / Thornton, Alicia / Myers, Richard / Schaefer, Ulf / Groves, Natalie / Gallagher, Eileen / Lee, David / Williams, David / Ellaby, Nicholas / Harrison, Ian / Hartman, Hassan / Manesis, Nikos / Patel, Vineet / Bishop, Chloe / Chalker, Vicki / Osman, Husam / Bosworth, Andrew / Robinson, Esther / Holden, Matthew T.G. / Shaaban, Sharif / Birchley, Alec / Adams, Alexander / Davies, Alisha / Gaskin, Amy / Plimmer, Amy / Gatica-Wilcox, Bree / McKerr, Caoimhe / Moore, Catherine / Williams, Chris / Heyburn, David / De Lacy, Elen / Hilvers, Ember / Downing, Fatima / Shankar, Giri / Jones, Hannah / Asad, Hibo / Coombes, Jason / Watkins, Joanne / Evans, Johnathan M. / Fina, Laia / Gifford, Laura / Gilbert, Lauren / Graham, Lee / Perry, Malorie / Morgan, Mari / Cronin, Michelle / Craine, Noel / Jones, Rachel / Howe, Robin / Corden, Sally / Rey, Sara / Kumziene-Summerhayes, Sara / Taylor, Sarah / Cottrell, Simon / Jones, Sophie / Edwards, Sue / O’Grady, Justin / Page, Andrew J. / Wain, John / Webber, Mark A. / Mather, Alison E. / Baker, David J. / Rudder, Steven / Yāsir, Muḥammad / Thomson, Nicholas M. / Aydin, Alp / Tedim, Ana P. / Kay, Gemma L. / Trotter, Alexander J. / Gilroy, Rachel A.J. / Alikhan, Nabil-Fareed / de Oliveira Martins, Leonardo / Le-Viet, Thanh / Meadows, Lizzie / Kolyva, Anastasia / Diaz, Maria / Bell, Andrew / Gutierrez, Ana Victoria / Charles, Ian G. / Adriaenssens, Evelien M. / Kingsley, Robert A. / Casey, Anna / Simpson, D. A. / Molnár, Zoltán / Thompson, Thomas / Acheson, Erwan / Masoli, Jane A.H. / Knight, Bridget A. / Hattersley, Andrew / Ellard, Sian / Auckland, Cressida / Mahungu, Tabitha W. / Irish-Tavares, Dianne / Haque, Tanzina / Bourgeois, Yann / Scarlett, Garry P. / Partridge, David G. / Raza, Mohammad / Evans, Cariad / Johnson, Kate / Liggett, Steven / Baker, Paul / Essex, Sarah / Lyons, Ronan A. / Caller, Laura G. / Castellano, Sergi / Williams, Rachel J. / Kristiansen, Mark / Roy, Sunando / Williams, Charlotte A. / Dyal, Patricia L. / Tutill, Helena J. / Panchbhaya, Yasmin N. / Forrest, Leysa M. / Niola, Paola / Findlay, Jacqueline / Brooks, Tony T. / Gavriil, Artemis / Mestek-Boukhibar, Lamia / Weeks, Sam / Pandey, Sarojini / Berry, Lisa / Jones, K. E. / Richter, Alex / Beggs, Andrew / Smith, Colin P. / Bucca, Giselda / Hesketh, Andrew R. / Harrison, Ewan M. / Peacock, Sharon J. / Eser, Sophie / Churcher, Carol M. / Bellis, Katherine L. / Girgis, Sophia T. / Naydenova, Plamena / Blane, Beth / Sridhar, Sushmita / Ruis, Chris / Forrest, Sally / Cormie, Claire / Gill, Harmeet K. / Dias, Joana / Higginson, Ellen E. / Maes, Mailis / Young, Jamie / Kermack, Leanne M. / Hadjirin, Nazreen F. / Aggarwal, Dinesh / Griffith, Luke / Swingler, Tracey / Davidson, Rose K. / Williams, Thomas / Balcazar, Carlos E. / Gallagher, Michael D. / O'Toole, Áine / Rooke, Stefan / Colquhoun, Rachel / Ashworth, Jordan / McCrone, J.T. / Scher, Emily / Yu, Xiaoyu / Williamson, Kathleen A. / Stanton, Thomas D. / Michell, Stephen L. / Bewshea, Claire M. / Temperton, Ben / Michelsen, Michelle L. / Warwick-Dugdale, Joanna / Manley, Robin / Farbos, Audrey / Harrison, James W. / Sambles, Christine M. / Studholme, David J. / Jeffries, Aaron R. / Darby, Alistair C. / Hiscox, Julian A. / Paterson, Steve / Iturriza-Gomara, Miren / Jackson, Kathryn A. / Lucaci, Anita O. / Vamos, Edith E. / Hughes, Margaret / Rainbow, Lucille / Eccles, Richard / Nelson, Charlotte / Whitehead, Mark / Turtle, Lance / Haldenby, Sam T. / Gregory, Richard / Gemmell, Matthew / Kwiatkowski, Dominic / de Silva, Thushan I. / Smith, Nikki / Angyal, Adrienn / Lindsey, Benjamin B. / Groves, Danielle C. / Green, Luke R. / Wang, Dennis / Freeman, Timothy M. / Parker, Matthew D. / Keeley, Alexander J. / Parsons, Paul J. / Tucker, Rachel M. / Brown, Rebecca / Wyles, Matthew / Constantinidou, Chrystala / Unnikrishnan, Meera / Ott, Sascha / Cheng, Jeffrey K.J. / Bridgewater, Hannah E. / Frost, Lucy R. / Taylor-Joyce, Grace / Stark, Richard / Baxter, Laura / Alam, Mohammad T. / Brown, Paul E. / McClure, Patrick C. / Chappell, Joseph G. / Tsoleridis, Theocharis / Ball, Jonathan / Gramatopoulos, Dimitris / Buck, David / Todd, John A. / Green, Angie / Trebes, Amy / MacIntyre-Cockett, George / de Cesare, Mariateresa / Langford, Cordelia / Alderton, Alex / Amato, Roberto / Goncalves, Sonia / Jackson, David K. / Johnston, Ian / Sillitoe, John / Palmer, Steve / Lawniczak, Mara / Berriman, Matt / Danesh, John / Livett, Rich / Shirley, Lesley / Farr, Ben / Quail, Mike / Thurston, Scott / Park, Naomi / Betteridge, Emma / Weldon, Danni / Goodwin, Scott / Nelson, Rachel / Beaver, Charlotte / Letchford, Laura / Jackson, David A. / Foulser, Luke / McMinn, Liz / Prestwood, Liam / Kay, Sally / Kane, Leanne / Dorman, Matthew J. / Martincorena, Inigo / Puethe, Christoph / Keatley, Jon-Paul / Tonkin-Hill, Gerry / Smith, Christen / Jamrozy, Dorota / Beale, Mathew A. / Patel, Minal / Ariani, Cristina / Spencer-Chapman, Michael / Drury, Eleanor / Lo, Stephanie / Rajatileka, Shavanthi / Scott, Carol / James, Keith / Buddenborg, Sarah K. / Berger, Duncan J. / Patel, Gaurang / Garcia-Casado, Maria V. / Dibling, Thomas / McGuigan, Samantha / Rogers, Hazel A. / Hunter, Adam D. / Souster, Emily / Neaverson, Alexandra S.

    Cell. 2021 Jan. 07, v. 184, no. 1 p.64-75.e11

    2021  

    Abstract: Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the ... ...

    Institution COG-UK Consortium
    Abstract Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; data collection ; founder effect ; genetic analysis ; genome ; mortality ; mutation ; pathogenicity ; phylogeny ; viral load ; United Kingdom ; COVID-19 ; SARS-CoV-2 ; evolution ; epidemiology ; spike
    Language English
    Dates of publication 2021-0107
    Size p. 64-75.e11.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note NAL-AP-2-clean
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2020.11.020
    Database NAL-Catalogue (AGRICOLA)

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