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1. Infection Inspection: using the power of citizen science for image-based prediction of antibiotic resistance in Escherichia coli treated with ciprofloxacin

Author: Alison Farrar, Conor Feehily, Piers Turner, Alexander Zagajewski, Stelios Chatzimichail, Derrick Crook, Monique Andersson, Sarah Oakley, Lucinda Barrett, Hafez El Sayyed, Philip W. Fowler, Christoffer Nellåker, Achillefs N. Kapanidis, and Nicole Stoesser
Subjects: Medicine, Science
Abstract: Abstract Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its threat. This study uses citizen science and image feature analysis to profile the cellular features associated with antibiotic resistance in Escherichia coli. Between February and April 2023, we conducted the Infection Inspection project, in which 5273 volunteers made 1,045,199 classifications of single-cell images from five E. coli strains, labelling them as antibiotic-sensitive or antibiotic-resistant based on their response to the antibiotic ciprofloxacin. User accuracy in image classification reached 66.8 ± 0.1%, lower than our deep learning model's performance at 75.3 ± 0.4%, but both users and the model were more accurate when classifying cells treated at a concentration greater than the strain’s own minimum inhibitory concentration. We used the users’ classifications to elucidate which visual features influence classification decisions, most importantly the degree of DNA compaction and heterogeneity. We paired our classification data with an image feature analysis which showed that most of the incorrect classifications happened when cellular features varied from the expected response. This understanding informs ongoing efforts to enhance the robustness of our diagnostic methodology. Infection Inspection is another demonstration of the potential for public participation in research, specifically increasing public awareness of antibiotic resistance.
Published: 2024
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2. The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies

Author: Samuel Lipworth, William Matlock, Liam Shaw, Karina-Doris Vihta, Gillian Rodger, Kevin Chau, Leanne Barker, Sophie George, James Kavanagh, Timothy Davies, Alison Vaughan, Monique Andersson, Katie Jeffery, Sarah Oakley, Marcus Morgan, Susan Hopkins, Timothy Peto, Derrick Crook, A. Sarah Walker, and Nicole Stoesser
Subjects: Science
Abstract: Abstract Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative ‘backbone’ of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.
Published: 2024
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3. Deep learning and single-cell phenotyping for rapid antimicrobial susceptibility detection in Escherichia coli

Author: Alexander Zagajewski, Piers Turner, Conor Feehily, Hafez El Sayyed, Monique Andersson, Lucinda Barrett, Sarah Oakley, Mathew Stracy, Derrick Crook, Christoffer Nellåker, Nicole Stoesser, and Achillefs N. Kapanidis
Subjects: Biology (General), QH301-705.5
Abstract: Abstract The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current culture-based turnaround times for bacterial identification in clinical samples and antimicrobial susceptibility testing (AST) are typically 18–24 h. We present a novel proof-of-concept methodological advance in susceptibility testing based on the deep-learning of single-cell specific morphological phenotypes directly associated with antimicrobial susceptibility in Escherichia coli. Our models can reliably (80% single-cell accuracy) classify untreated and treated susceptible cells for a lab-reference fully susceptible E. coli strain, across four antibiotics (ciprofloxacin, gentamicin, rifampicin and co-amoxiclav). For ciprofloxacin, we demonstrate our models reveal significant (p
Published: 2023
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4. A consensus statement on dual purpose pathogen surveillance systems: The always on approach.

Author: Helene-Mari van der Westhuizen, Srinidhi Soundararajan, Tamsin Berry, David Agus, Sergio Carmona, Philip Ma, Jessica Davis, Sarah Walker, Jolynne Mokaya, Stephen D Bentley, Nick R Thomson, John Silitoe, Andrew Singer, Ines Hassan, Romina Mariano, Megan Akodu, Gabriel Seidman, Nabihah Sachedina, Jonathan Edgeworth, Reshania Naidoo, Tariro Makadzange, Vladimir Choi, Renuka Gadde, Samuel V Scarpino, Corinna Bull, Kumeren Govender, Belinda Ngongo, Hinda Ruton, Paul Pronyk, Kate Smolina, Henry Li, Dylan Barry, Sven Schaffer, Vanessa Moeder, George Gao, Derrick Crook, and John Bell
Subjects: Public aspects of medicine, RA1-1270
Published: 2024
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5. Author Correction: The plasmidome associated with Gram-negative bloodstream infections: a large-scale observational study using complete plasmid assemblies

Author: Samuel Lipworth, William Matlock, Liam Shaw, Karina-Doris Vihta, Gillian Rodger, Kevin Chau, Leanne Barker, Sophie George, James Kavanagh, Timothy Davies, Alison Vaughan, Monique Andersson, Katie Jeffery, Sarah Oakley, Marcus Morgan, Susan Hopkins, Timothy Peto, Derrick Crook, A. Sarah Walker, and Nicole Stoesser
Subjects: Science
Published: 2024
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6. Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria

Author: Sam Lipworth, Karina-Doris Vihta, Tim Davies, Sarah Wright, Merline Tabirao, Kevin Chau, Alison Vaughan, James Kavanagh, Leanne Barker, Sophie George, Shelley Segal, Stephane Paulus, Lucinda Barrett, Sarah Oakley, Katie Jeffery, Lisa Butcher, Tim Peto, Derrick Crook, Sarah Walker, Seilesh Kadambari, and Nicole Stoesser
Subjects: Medicine
Abstract: Lipworth et al. conduct a molecular epidemiological analysis of Gram-negative bloodstream infections in children in Oxfordshire, England, over a 10-year period. The authors report E. coli as the main causative agent and observe a similar population structure to that seen in adult infections with a stable incidence of antimicrobial resistance.
Published: 2022
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7. Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales

Author: Kalisvar Marimuthu, Indumathi Venkatachalam, Vanessa Koh, Stephan Harbarth, Eli Perencevich, Benjamin Pei Zhi Cherng, Raymond Kok Choon Fong, Surinder Kaur Pada, Say Tat Ooi, Nares Smitasin, Koh Cheng Thoon, Paul Anantharajah Tambyah, Li Yang Hsu, Tse Hsien Koh, Partha Pratim De, Thean Yen Tan, Douglas Chan, Rama Narayana Deepak, Nancy Wen Sim Tee, Andrea Kwa, Yiying Cai, Yik-Ying Teo, Natascha May Thevasagayam, Sai Rama Sridatta Prakki, Weizhen Xu, Wei Xin Khong, David Henderson, Nicole Stoesser, David W. Eyre, Derrick Crook, Michelle Ang, Raymond Tzer Pin Lin, Angela Chow, Alex R. Cook, Jeanette Teo, Oon Tek Ng, and Carbapenemase-Producing Enterobacteriaceae in Singapore (CaPES) Study Group
Subjects: Science
Abstract: Carbapenemase-producing Enterobacterales cause healthcare-associated infections but modes of transmission are not well understood. Here, the authors find evidence of transmission without direct patient contact, indicating presence of undetected environmental reservoirs, whilst half of the transmission events are likely due to plasmid-mediated transmission.
Published: 2022
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8. Antimicrobial resistance in commensal opportunistic pathogens isolated from non-sterile sites can be an effective proxy for surveillance in bloodstream infections

Author: Karina-Doris Vihta, Nicola Claire Gordon, Nicole Stoesser, T. Phuong Quan, Carina S. B. Tyrrell, Manivanh Vongsouvath, Elizabeth A. Ashley, Vilada Chansamouth, Paul Turner, Clare L. Ling, David W. Eyre, Nicholas J. White, Derrick Crook, Tim E. A. Peto, and Ann Sarah Walker
Subjects: Medicine, Science
Abstract: Abstract Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998–2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51–0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004–2017) and three further LMIC hospitals/programmes (6154 isolates, 2008–2019). AMR in commensal opportunistic pathogens cultured from BSIs is strongly associated with AMR in commensal opportunistic pathogens cultured from non-sterile sites over calendar time, suggesting the latter could be used as an effective proxy for AMR surveillance in BSIs.
Published: 2021
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9. Viral detection and identification in 20 min by rapid single-particle fluorescence in-situ hybridization of viral RNA

Author: Christof Hepp, Nicolas Shiaelis, Nicole C. Robb, Alison Vaughan, Philippa C. Matthews, Nicole Stoesser, Derrick Crook, and Achillefs N. Kapanidis
Subjects: Medicine, Science
Abstract: Abstract The increasing risk from viral outbreaks such as the ongoing COVID-19 pandemic exacerbates the need for rapid, affordable and sensitive methods for virus detection, identification and quantification; however, existing methods for detecting virus particles in biological samples usually depend on multistep protocols that take considerable time to yield a result. Here, we introduce a rapid fluorescence in situ hybridization (FISH) protocol capable of detecting influenza virus, avian infectious bronchitis virus and SARS-CoV-2 specifically and quantitatively in approximately 20 min, in virus cultures, combined nasal and throat swabs with added virus and likely patient samples without previous purification. This fast and facile workflow can be adapted both as a lab technique and a future diagnostic tool in enveloped viruses with an accessible genome.
Published: 2021
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10. A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Author: Alain Townsend, Pramila Rijal, Julie Xiao, Tiong Kit Tan, Kuan-Ying A. Huang, Lisa Schimanski, Jiandong Huo, Nimesh Gupta, Rolle Rahikainen, Philippa C. Matthews, Derrick Crook, Sarah Hoosdally, Susanna Dunachie, Eleanor Barnes, Teresa Street, Christopher P. Conlon, John Frater, Carolina V. Arancibia-Cárcamo, Justine Rudkin, Nicole Stoesser, Fredrik Karpe, Matthew Neville, Rutger Ploeg, Marta Oliveira, David J. Roberts, Abigail A. Lamikanra, Hoi Pat Tsang, Abbie Bown, Richard Vipond, Alexander J. Mentzer, Julian C. Knight, Andrew J. Kwok, Gavin R. Screaton, Juthathip Mongkolsapaya, Wanwisa Dejnirattisai, Piyada Supasa, Paul Klenerman, Christina Dold, J. Kenneth Baillie, Shona C. Moore, Peter J. M. Openshaw, Malcolm G. Semple, Lance C. W. Turtle, Mark Ainsworth, Alice Allcock, Sally Beer, Sagida Bibi, Donal Skelly, Lizzy Stafford, Katie Jeffrey, Denise O’Donnell, Elizabeth Clutterbuck, Alexis Espinosa, Maria Mendoza, Dominique Georgiou, Teresa Lockett, Jose Martinez, Elena Perez, Veronica Gallardo Sanchez, Giuseppe Scozzafava, Alberto Sobrinodiaz, Hannah Thraves, and Etienne Joly
Subjects: Science
Abstract: Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.
Published: 2021
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11. Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study

Author: T. Phuong Quan, Berit Muller-Pebody, Nicola Fawcett, Bernadette C. Young, Mehdi Minaji, Jonathan Sandoe, Susan Hopkins, Derrick Crook, Timothy Peto, Alan P. Johnson, and A. Sarah Walker
Subjects: Infective endocarditis, Dental procedures, Antibiotic prophylaxis, Electronic health records, EHR, Medicine
Abstract: Abstract Background Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change. Methods Using national data from Hospital Episode Statistics covering 1998–2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date. Results Infective endocarditis incidence increased markedly over the study (22.2–41.3 per million population in 1998 to 42.0–67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000–May 2003) to May 2015 (March 1999–January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006–April 2010) to August 2015 (September 2013–November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date. Conclusions Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase.
Published: 2020
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12. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Author: Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova, Lidia M. Duncan, Alessandro M. Carabelli, Julia C. Kenyon, Andrew M. Lever, Anna De Marco, Christian Saliba, Katja Culap, Elisabetta Cameroni, Nicholas J. Matheson, Luca Piccoli, Davide Corti, Leo C. James, David L. Robertson, Dalan Bailey, Ravindra K. Gupta, Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally Corden, Ian Johnston, David Bonsall, Colin P. Smith, Ali R. Awan, Giselda Bucca, M. Estee Torok, Kordo Saeed, Jacqui A. Prieto, David K. Jackson, William L. Hamilton, Luke B. Snell, Catherine Moore, Ewan M. Harrison, Sonia Goncalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Rich Livett, Samuel Moses, Roberto Amato, Sam Nicholls, Matthew Bull, Darren L. Smith, Jeff Barrett, David M. Aanensen, Martin D. Curran, Surendra Parmar, Dinesh Aggarwal, James G. Shepherd, Matthew D. Parker, Sharon Glaysher, Matthew Bashton, Anthony P. Underwood, Nicole Pacchiarini, Katie F. Loveson, Kate E. Templeton, Cordelia F. Langford, John Sillitoe, Thushan I. de Silva, Dennis Wang, Dominic Kwiatkowski, Andrew Rambaut, Justin O’Grady, Simon Cottrell, Matthew T.G. Holden, Emma C. Thomson, Husam Osman, Monique Andersson, Anoop J. Chauhan, Mohammed O. Hassan-Ibrahim, Mara Lawniczak, Alex Alderton, Meera Chand, Chrystala Constantinidou, Meera Unnikrishnan, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Inigo Martincorena, Erik M. Volz, Andrew J. Page, Oliver G. Pybus, Andrew R. Bassett, Cristina V. Ariani, Michael H. Spencer Chapman, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yusri Taha, Martin P. McHugh, Rebecca Dewar, Aminu S. Jahun, Claire McMurray, Sarojini Pandey, James P. McKenna, Andrew Nelson, Gregory R. Young, Clare M. McCann, Scott Elliott, Hannah Lowe, Ben Temperton, Sunando Roy, Anna Price, Sara Rey, Matthew Wyles, Stefan Rooke, Sharif Shaaban, Mariateresa de Cesare, Laura Letchford, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Myra Hosmillo, Áine O’Toole, Andrew R. Hesketh, Richard Stark, Louis du Plessis, Chris Ruis, Helen Adams, Yann Bourgeois, Stephen L. Michell, Dimitris Gramatopoulos, Jonathan Edgeworth, Judith Breuer, John A. Todd, Christophe Fraser, David Buck, Michaela John, Gemma L. Kay, Steve Palmer, Sharon J. Peacock, David Heyburn, Danni Weldon, Esther Robinson, Alan McNally, Peter Muir, Ian B. Vipond, John Boyes, Venkat Sivaprakasam, Tranprit Salluja, Samir Dervisevic, Emma J. Meader, Naomi R. Park, Karen Oliver, Aaron R. Jeffries, Sascha Ott, Ana da Silva Filipe, David A. Simpson, Chris Williams, Jane A.H. Masoli, Bridget A. Knight, Christopher R. Jones, Cherian Koshy, Amy Ash, Anna Casey, Andrew Bosworth, Liz Ratcliffe, Li Xu-McCrae, Hannah M. Pymont, Stephanie Hutchings, Lisa Berry, Katie Jones, Fenella Halstead, Thomas Davis, Christopher Holmes, Miren Iturriza-Gomara, Anita O. Lucaci, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Kathryn Ann Harris, Julianne Rose Brown, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Steven Liggett, Clive Graham, Emma Swindells, Jennifer Collins, Gary Eltringham, Sharon Campbell, Patrick C. McClure, Gemma Clark, Tim J. Sloan, Carl Jones, Jessica Lynch, Ben Warne, Steven Leonard, Jillian Durham, Thomas Williams, Sam T. Haldenby, Nathaniel Storey, Nabil-Fareed Alikhan, Nadine Holmes, Christopher Moore, Matthew Carlile, Malorie Perry, Noel Craine, Ronan A. Lyons, Angela H. Beckett, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, Robert Davies, Beth Blane, Sophia T. Girgis, Mathew A. Beale, Katherine L. Bellis, Matthew J. Dorman, Eleanor Drury, Leanne Kane, Sally Kay, Samantha McGuigan, Rachel Nelson, Liam Prestwood, Shavanthi Rajatileka, Rahul Batra, Rachel J. Williams, Mark Kristiansen, Angie Green, Anita Justice, Adhyana I.K. Mahanama, Buddhini Samaraweera, Nazreen F. Hadjirin, Joshua Quick, Radoslaw Poplawski, Leanne M. Kermack, Nicola Reynolds, Grant Hall, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Robin J. Moll, Alicia Thornton, Richard Myers, Joanne Stockton, Charlotte A. Williams, Wen C. Yew, Alexander J. Trotter, Amy Trebes, George MacIntyre-Cockett, Alec Birchley, Alexander Adams, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Ember Hilvers, Hannah Jones, Hibo Asad, Jason Coombes, Johnathan M. Evans, Laia Fina, Lauren Gilbert, Lee Graham, Michelle Cronin, Sara Kumziene-Summerhayes, Sarah Taylor, Sophie Jones, Danielle C. Groves, Peijun Zhang, Marta Gallis, Stavroula F. Louka, Igor Starinskij, Chris Jackson, Marina Gourtovaia, Gerry Tonkin-Hill, Kevin Lewis, Jaime M. Tovar-Corona, Keith James, Laura Baxter, Mohammad T. Alam, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Olivia Boyd, Lily Geidelberg, Alex E. Zarebski, Jayna Raghwani, Moritz U.G. Kraemer, Joel Southgate, Benjamin B. Lindsey, Timothy M. Freeman, Jon-Paul Keatley, Joshua B. Singer, Leonardo de Oliveira Martins, Corin A. Yeats, Khalil Abudahab, Ben E.W. Taylor, Mirko Menegazzo, John Danesh, Wendy Hogsden, Sahar Eldirdiri, Anita Kenyon, Jenifer Mason, Trevor I. Robinson, Alison Holmes, James Price, John A. Hartley, Tanya Curran, Alison E. Mather, Giri Shankar, Rachel Jones, Robin Howe, Sian Morgan, Elizabeth Wastenge, Michael R. Chapman, Siddharth Mookerjee, Rachael Stanley, Wendy Smith, Timothy Peto, David Eyre, Derrick Crook, Gabrielle Vernet, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Declan T. Bradley, Tim Wyatt, Charlotte Beaver, Luke Foulser, Sophie Palmer, Carol M. Churcher, Ellena Brooks, Kim S. Smith, Katerina Galai, Georgina M. McManus, Frances Bolt, Francesc Coll, Lizzie Meadows, Stephen W. Attwood, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Garry P. Scarlett, Sarah Jeremiah, Nikki Smith, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Michelle Wantoch, Dorota Jamrozy, Stephanie Lo, Minal Patel, Verity Hill, Claire M. Bewshea, Sian Ellard, Cressida Auckland, Ian Harrison, Chloe Bishop, Vicki Chalker, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Richard Hopes, Patawee Asamaphan, Marc O. Niebel, Rory N. Gunson, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Holli Carden, Nicholas W. Machin, Kathryn A. Jackson, Shazaad S.Y. Ahmad, Ryan P. George, Lance Turtle, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Adela Alcolea-Medina, Themoula Charalampous, Amita Patel, Lisa J. Levett, Judith Heaney, Aileen Rowan, Graham P. Taylor, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adam P. Westhorpe, Riaz Jannoo, Helen L. Lowe, Angeliki Karamani, Leah Ensell, Wendy Chatterton, Monika Pusok, Ashok Dadrah, Amanda Symmonds, Graciela Sluga, Zoltan Molnar, Paul Baker, Stephen Bonner, Sarah Essex, Edward Barton, Debra Padgett, Garren Scott, Jane Greenaway, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Veena Raviprakash, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Jonathan Moore, Susanne Stonehouse, Louise Smith, Rose K. Davidson, Luke Bedford, Lindsay Coupland, Victoria Wright, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Nichola Duckworth, Sarah Walsh, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Stephen Kidd, Rebecca Williams, Laura Gifford, Kelly Bicknell, Sarah Wyllie, Allyson Lloyd, Robert Impey, Cassandra S. Malone, Benjamin J. Cogger, Nick Levene, Lynn Monaghan, Alexander J. Keeley, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Emma Betteridge, Ben W. Farr, Scott Goodwin, Michael A. Quail, Carol Scott, Lesley Shirley, Scott A.J. Thurston, Diana Rajan, Iraad F. Bronner, Louise Aigrain, Nicholas M. Redshaw, Stefanie V. Lensing, Shane McCarthy, Alex Makunin, Carlos E. Balcazar, Michael D. Gallagher, Kathleen A. Williamson, Thomas D. Stanton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine M. Sambles, David J. Studholme, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Hassan Hartman, Nikos Manesis, Vineet Patel, Juan Ledesma, Katherine A. Twohig, Elias Allara, Clare Pearson, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Paul E. Brown, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Katherine L. Smollett, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Seema Nickbakhsh, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J. Webster, Chloe L. Fisher, Adrian W. Signell, Gilberto Betancor, Harry D. Wilson, Gaia Nebbia, Flavia Flaviani, Alberto C. Cerda, Tammy V. Merrill, Rebekah E. Wilson, Marius Cotic, Nadua Bayzid, Thomas Thompson, Erwan Acheson, Steven Rushton, Sarah O’Brien, David J. Baker, Steven Rudder, Alp Aydin, Fei Sang, Johnny Debebe, Sarah Francois, Tetyana I. Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, Angela Marchbank, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Mari Morgan, Robert Beer, Safiah Afifi, Trudy Workman, William Fuller, Catherine Bresner, Adrienn Angyal, Luke R. Green, Paul J. Parsons, Rachel M. Tucker, Rebecca Brown, Max Whiteley, James Bonfield, Christoph Puethe, Andrew Whitwham, Jennifier Liddle, Will Rowe, Igor Siveroni, Thanh Le-Viet, Amy Gaskin, Rob Johnson, Irina Abnizova, Mozam Ali, Laura Allen, Ralph Anderson, Cristina Ariani, Siobhan Austin-Guest, Sendu Bala, Jeffrey Barrett, Andrew Bassett, Kristina Battleday, James Beal, Mathew Beale, Sam Bellany, Tristram Bellerby, Katie Bellis, Duncan Berger, Matt Berriman, Paul Bevan, Simon Binley, Jason Bishop, Kirsty Blackburn, Nick Boughton, Sam Bowker, Timothy Brendler-Spaeth, Iraad Bronner, Tanya Brooklyn, Sarah Kay Buddenborg, Robert Bush, Catarina Caetano, Alex Cagan, Nicola Carter, Joanna Cartwright, Tiago Carvalho Monteiro, Liz Chapman, Tracey-Jane Chillingworth, Peter Clapham, Richard Clark, Adrian Clarke, Catriona Clarke, Daryl Cole, Elizabeth Cook, Maria Coppola, Linda Cornell, Clare Cornwell, Craig Corton, Abby Crackett, Alison Cranage, Harriet Craven, Sarah Craw, Mark Crawford, Tim Cutts, Monika Dabrowska, Matt Davies, Joseph Dawson, Callum Day, Aiden Densem, Thomas Dibling, Cat Dockree, David Dodd, Sunil Dogga, Matthew Dorman, Gordon Dougan, Martin Dougherty, Alexander Dove, Lucy Drummond, Monika Dudek, Laura Durrant, Elizabeth Easthope, Sabine Eckert, Pete Ellis, Ben Farr, Michael Fenton, Marcella Ferrero, Neil Flack, Howerd Fordham, Grace Forsythe, Matt Francis, Audrey Fraser, Adam Freeman, Anastasia Galvin, Maria Garcia-Casado, Alex Gedny, Sophia Girgis, James Glover, Oliver Gould, Andy Gray, Emma Gray, Coline Griffiths, Yong Gu, Florence Guerin, Will Hamilton, Hannah Hanks, Ewan Harrison, Alexandria Harrott, Edward Harry, Julia Harvison, Paul Heath, Anastasia Hernandez-Koutoucheva, Rhiannon Hobbs, Dave Holland, Sarah Holmes, Gary Hornett, Nicholas Hough, Liz Huckle, Lena Hughes-Hallet, Adam Hunter, Stephen Inglis, Sameena Iqbal, Adam Jackson, David Jackson, Carlos Jimenez Verdejo, Matthew Jones, Kalyan Kallepally, Keely Kay, Jon Keatley, Alan Keith, Alison King, Lucy Kitchin, Matt Kleanthous, Martina Klimekova, Petra Korlevic, Ksenia Krasheninnkova, Greg Lane, Cordelia Langford, Adam Laverack, Katharine Law, Stefanie Lensing, Amanah Lewis-Wade, Jennifer Liddle, Quan Lin, Sarah Lindsay, Sally Linsdell, Rhona Long, Jamie Lovell, Jon Lovell, James Mack, Mark Maddison, Aleksei Makunin, Irfan Mamun, Jenny Mansfield, Neil Marriott, Matt Martin, Matthew Mayho, Jo McClintock, Sandra McHugh, Liz MapcMinn, Carl Meadows, Emily Mobley, Robin Moll, Maria Morra, Leanne Morrow, Kathryn Murie, Sian Nash, Claire Nathwani, Plamena Naydenova, Alexandra Neaverson, Ed Nerou, Jon Nicholson, Tabea Nimz, Guillaume G. Noell, Sarah O’Meara, Valeriu Ohan, Charles Olney, Doug Ormond, Agnes Oszlanczi, Yoke Fei Pang, Barbora Pardubska, Naomi Park, Aaron Parmar, Gaurang Patel, Maggie Payne, Sharon Peacock, Arabella Petersen, Deborah Plowman, Tom Preston, Michael Quail, Richard Rance, Suzannah Rawlings, Nicholas Redshaw, Joe Reynolds, Mark Reynolds, Simon Rice, Matt Richardson, Connor Roberts, Katrina Robinson, Melanie Robinson, David Robinson, Hazel Rogers, Eduardo Martin Rojo, Daljit Roopra, Mark Rose, Luke Rudd, Ramin Sadri, Nicholas Salmon, David Saul, Frank Schwach, Phil Seekings, Alison Simms, Matt Sinnott, Shanthi Sivadasan, Bart Siwek, Dale Sizer, Kenneth Skeldon, Jason Skelton, Joanna Slater-Tunstill, Lisa Sloper, Nathalie Smerdon, Chris Smith, Christen Smith, James Smith, Katie Smith, Michelle Smith, Sean Smith, Tina Smith, Leighton Sneade, Carmen Diaz Soria, Catarina Sousa, Emily Souster, Andrew Sparkes, Michael Spencer-Chapman, Janet Squares, Robert Stanley, Claire Steed, Tim Stickland, Ian Still, Mike Stratton, Michelle Strickland, Allen Swann, Agnieszka Swiatkowska, Neil Sycamore, Emma Swift, Edward Symons, Suzanne Szluha, Emma Taluy, Nunu Tao, Katy Taylor, Sam Taylor, Stacey Thompson, Mark Thompson, Mark Thomson, Nicholas Thomson, Scott Thurston, Dee Toombs, Benjamin Topping, Jaime Tovar-Corona, Daniel Ungureanu, James Uphill, Jana Urbanova, Philip Jansen Van, Valerie Vancollie, Paul Voak, Danielle Walker, Matthew Walker, Matt Waller, Gary Ward, Charlie Weatherhogg, Niki Webb, Alan Wells, Eloise Wells, Luke Westwood, Theo Whipp, Thomas Whiteley, Georgia Whitton, Sara Widaa, Mia Williams, Mark Wilson, and Sean Wright
Subjects: SARS-CoV-2, COVID-19, antibody escape, neutralizing antibodies, infectivity, spike mutation, Biology (General), QH301-705.5
Abstract: Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.
Published: 2021
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13. Antibiotic Review Kit for Hospitals (ARK-Hospital): study protocol for a stepped-wedge cluster-randomised controlled trial

Author: Ann Sarah Walker, Eric Budgell, Magda Laskawiec-Szkonter, Katy Sivyer, Sarah Wordsworth, Jack Quaddy, Marta Santillo, Adele Krusche, Laurence S. J. Roope, Nicole Bright, Fiona Mowbray, Nicola Jones, Kieran Hand, Najib Rahman, Melissa Dobson, Emma Hedley, Derrick Crook, Mike Sharland, Chris Roseveare, F. D. Richard Hobbs, Chris Butler, Louella Vaughan, Susan Hopkins, Lucy Yardley, Timothy E. A. Peto, Martin J. Llewelyn, and on behalf of the ARK trial team
Subjects: Antibiotic prescribing, Hospitals, Antimicrobial stewardship, Medicine (General), R5-920
Abstract: Abstract Background To ensure patients continue to get early access to antibiotics at admission, while also safely reducing antibiotic use in hospitals, one needs to target the continued need for antibiotics as more diagnostic information becomes available. UK Department of Health guidance promotes an initiative called ‘Start Smart then Focus’: early effective antibiotics followed by active ‘review and revision’ 24–72 h later. However in 2017,
Published: 2019
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14. SNP-IT Tool for Identifying Subspecies and Associated Lineages of Mycobacterium tuberculosis Complex

Author: Samuel Lipworth, Rana Jajou, Albert de Neeling, Phelim Bradley, Wim van der Hoek, Gugu Maphalala, Maryline Bonnet, Elizabeth Sanchez-Padilla, Roland Diel, Stefan Niemann, Zamin Iqbal, Grace Smith, Tim Peto, Derrick Crook, Timothy Walker, and Dick van Soolingen
Subjects: tuberculosis, whole genome sequencing, zoonoses, phylogeny, single nucleotide polymorphism, SNP-IT, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: The clinical phenotype of zoonotic tuberculosis and its contribution to the global burden of disease are poorly understood and probably underestimated. This shortcoming is partly because of the inability of currently available laboratory and in silico tools to accurately identify all subspecies of the Mycobacterium tuberculosis complex (MTBC). We present SNPs to Identify TB (SNP-IT), a single-nucleotide polymorphism–based tool to identify all members of MTBC, including animal clades. By applying SNP-IT to a collection of clinical genomes from a UK reference laboratory, we detected an unexpectedly high number of M. orygis isolates. M. orygis is seen at a similar rate to M. bovis, yet M. orygis cases have not been previously described in the United Kingdom. From an international perspective, it is possible that M. orygis is an underestimated zoonosis. Accurate identification will enable study of the clinical phenotype, host range, and transmission mechanisms of all subspecies of MTBC in greater detail.
Published: 2019
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15. Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Author: 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, and Rory N Gunson
Subjects: Public aspects of medicine, RA1-1270
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.
Published: 2021
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16. Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study

Author: Malick M Gibani, D Phil, Christofer Toumazou, ProfPhD, Mohammadreza Sohbati, PhD, Rashmita Sahoo, PhD, Maria Karvela, PhD, Tsz-Kin Hon, PhD, Sara De Mateo, PhD, Alison Burdett, PhD, K Y Felice Leung, PhD, Jake Barnett, MSc, Arman Orbeladze, MSc, Song Luan, PhD, Stavros Pournias, MSc, Jiayang Sun, MSc, Barney Flower, MRCP, Judith Bedzo-Nutakor, BSc, Maisarah Amran, MBBS, Rachael Quinlan, BSc, Keira Skolimowska, PhD, Carolina Herrera, PhD, Aileen Rowan, PhD, Anjna Badhan, PhD, Robert Klaber, MD, Gary Davies, MD, David Muir, FRCPath, Paul Randell, FRCPath, Derrick Crook, ProfFRCPath, Graham P Taylor, ProfDSc, Wendy Barclay, ProfPhD, Nabeela Mughal, FRCPath, Luke S P Moore, PhD, Katie Jeffery, PhD, and Graham S Cooke, ProfFRCP
Subjects: Medicine (General), R5-920, Microbiology, QR1-502
Abstract: Summary: Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86–98) with an overall specificity of 100% (99–100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85–98]; patients in the emergency department 100% [48–100]; and hospital inpatient admissions 100% [29–100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98–100]; patients in the emergency department 100% [69–100]; and hospital inpatient admissions 100% [96–100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20–31] in April, 2020) and low prevalence (3% [95% 1–9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA. Interpretation: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes. Funding: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.
Published: 2020
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17. SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus [version 2; peer review: 2 approved]

Author: Monique I. Andersson, Carolina V. Arancibia-Carcamo, Kathryn Auckland, J. Kenneth Baillie, Eleanor Barnes, Tom Beneke, Sagida Bibi, Tim Brooks, Miles Carroll, Derrick Crook, Kate Dingle, Christina Dold, Louise O. Downs, Laura Dunn, David W. Eyre, Javier Gilbert Jaramillo, Heli Harvala, Sarah Hoosdally, Samreen Ijaz, Tim James, William James, Katie Jeffery, Anita Justice, Paul Klenerman, Julian C. Knight, Michael Knight, Xu Liu, Sheila F. Lumley, Philippa C. Matthews, Anna L. McNaughton, Alexander J. Mentzer, Juthathip Mongkolsapaya, Sarah Oakley, Marta S. Oliveira, Timothy Peto, Rutger J. Ploeg, Jeremy Ratcliff, Melanie J. Robbins, David J. Roberts, Justine Rudkin, Rebecca A. Russell, Gavin Screaton, Malcolm G. Semple, Donal Skelly, Peter Simmonds, Nicole Stoesser, Lance Turtle, Susan Wareing, and Maria Zambon
Subjects: Medicine, Science
Abstract: Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.
Published: 2020
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18. Case Report: Disseminated, rifampicin resistant Mycobacterium bovis (BCG) infection in an immunocompromised child [version 1; peer review: 2 approved]

Author: Simon B. Drysdale, Dominic F. Kelly, Marcus Morgan, Tim Peto, Derrick Crook, Philippa C. Matthews, and Timothy M. Walker
Subjects: Medicine, Science
Abstract: Background: Bacillus Calmette–Guérin (BCG) is a live-attenuated vaccine used world-wide for prevention of tuberculosis disease. In some immunocompromised hosts it has the potential to cause disease. As with other members of the M. tuberculosis complex it has the potential for acquiring drug resistance. Methods: We reviewed 10 years of paediatric clinical BCG strains referred to our clinical microbiology laboratory in Oxford where they underwent whole genome sequencing. We present a case series comparing clinical, pathogen genetic and pathogen phenotypic data, and consider the clinical implications. Results: We identified 15 BCG isolates from 8 children under 16 years old. Only one child had clinical disease with the other seven reported as local inoculation-site reactions. Case 1 suffered disseminated disease secondary to an undiagnosed IL-12/IFNγ receptor defect and the BCG isolates evolved two different rifampicin resistance mutations. Across all 15 isolates, phenotypic resistance to each first line drug was seen. Conclusions: BCG is a safe and effective vaccine in children. Most clinical specimens in our series were not related to disease. However, in the context of rare pathogen-specific immunocompromise, BCG can cause pathology and acquire drug resistance under selection from therapy.
Published: 2020
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19. BugMat and FindNeighbour: command line and server applications for investigating bacterial relatedness

Author: Oriol Mazariegos-Canellas, Trien Do, Tim Peto, David W. Eyre, Anthony Underwood, Derrick Crook, and David H. Wyllie
Subjects: Bacterial genomes, Phylogenetic analysis, Distance matrix, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract: Abstract Background Large scale bacterial sequencing has made the determination of genetic relationships within large sequence collections of bacterial genomes derived from the same microbial species an increasingly common task. Solutions to the problem have application to public health (for example, in the detection of possible disease transmission), and as part of divide-and-conquer strategies selecting groups of similar isolates for computationally intensive methods of phylogenetic inference using (for example) maximal likelihood methods. However, the generation and maintenance of distance matrices is computationally intensive, and rapid methods of doing so are needed to allow translation of microbial genomics into public health actions. Results We developed, tested and deployed three solutions. BugMat is a fast C++ application which generates one-off in-memory distance matrices. FindNeighbour and FindNeighbour2 are server-side applications which build, maintain, and persist either complete (for FindNeighbour) or sparse (for FindNeighbour2) distance matrices given a set of sequences. FindNeighbour and BugMat use a variation model to accelerate computation, while FindNeighbour2 uses reference-based compression. Performance metrics show scalability into tens of thousands of sequences, with options for scaling further. Conclusion Three applications, each with distinct strengths and weaknesses, are available for distance-matrix based analysis of large bacterial collections. Deployed as part of the Public Health England solution for M. tuberculosis genomic processing, they will have wide applicability.
Published: 2017
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20. A curated dataset of complete Enterobacteriaceae plasmids compiled from the NCBI nucleotide database

Author: Alex Orlek, Hang Phan, Anna E. Sheppard, Michel Doumith, Matthew Ellington, Tim Peto, Derrick Crook, A. Sarah Walker, Neil Woodford, Muna F. Anjum, and Nicole Stoesser
Subjects: Plasmids, Sequence data curation, Complete genomes, Enterobacteriaceae family, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract: Thousands of plasmid sequences are now publicly available in the NCBI nucleotide database, but they are not reliably annotated to distinguish complete plasmids from plasmid fragments, such as gene or contig sequences; therefore, retrieving complete plasmids for downstream analyses is challenging. Here we present a curated dataset of complete bacterial plasmids from the clinically relevant Enterobacteriaceae family. The dataset was compiled from the NCBI nucleotide database using curation steps designed to exclude incomplete plasmid sequences, and chromosomal sequences misannotated as plasmids. Over 2000 complete plasmid sequences are included in the curated plasmid dataset. Protein sequences produced from translating each complete plasmid nucleotide sequence in all 6 frames are also provided. Further analysis and discussion of the dataset is presented in an accompanying research article: “Ordering the mob: insights into replicon and MOB typing…” (Orlek et al., 2017) [1]. The curated plasmid sequences are publicly available in the Figshare repository.
Published: 2017
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21. Detection of Viral Pathogens With Multiplex Nanopore MinION Sequencing: Be Careful With Cross-Talk

Author: Yifei Xu, Kuiama Lewandowski, Sheila Lumley, Steven Pullan, Richard Vipond, Miles Carroll, Dona Foster, Philippa C. Matthews, Timothy Peto, and Derrick Crook
Subjects: nanopore sequencing, metagenomics, multiplexing, cross barcode contamination, chimera, Microbiology, QR1-502
Abstract: Metagenomic sequencing with the Oxford Nanopore MinION sequencer offers potential for point-of-care testing of infectious diseases in clinical settings. To improve cost-effectiveness, multiplexing of several, barcoded samples upon a single flow cell will be required during sequencing. We generated a unique sequencing dataset to assess the extent and source of cross barcode contamination caused by multiplex MinION sequencing. Sequencing libraries for three different viruses, including influenza A, dengue, and chikungunya, were prepared separately and sequenced on individual flow cells. We also pooled the respective libraries and performed multiplex sequencing. We identified 0.056% of total reads in the multiplex sequencing data that were assigned to incorrect barcodes. Chimeric reads were the predominant source of this error. Our findings highlight the need for careful filtering of multiplex sequencing data before downstream analysis, and the trade-off between sensitivity and specificity that applies to the barcode demultiplexing methods.
Published: 2018
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22. Using linked electronic health records to report healthcare-associated infections.

Author: T Phuong Quan, Russell Hope, Tiphanie Clarke, Ruth Moroney, Lisa Butcher, Peter Knight, Derrick Crook, Susan Hopkins, Timothy E A Peto, Alan P Johnson, and A Sarah Walker
Subjects: Medicine, Science
Abstract: BACKGROUND:Reporting of strategic healthcare-associated infections (HCAIs) to Public Health England is mandatory for all acute hospital trusts in England, via a web-based HCAI Data Capture System (HCAI-DCS). AIM:Investigate the feasibility of automating the current, manual, HCAI reporting using linked electronic health records (linked-EHR), and assess its level of accuracy. METHODS:All data previously submitted through the HCAI-DCS by the Oxford University Hospitals infection control (IC) team for methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA, MSSA), Clostridium difficile, and Escherichia coli, through March 2017 were downloaded and compared to outputs created from linked-EHR, with detailed comparisons between 2013-2017. FINDINGS:Total MRSA, MSSA, E. coli and C. difficile cases entered by the IC team vs linked-EHR were 428 vs 432, 795 vs 816, 2454 vs 2450 and 3365 vs 3393 respectively. From 2013-2017, most discrepancies (32/37 (86%)) were likely due to IC recording errors. Patient and specimen identifiers were completed for >98% of cases by both methods, with very high agreement (>97%). Fields relating to the patient at the time the specimen was taken were complete to a similarly high level (>99% IC, >97% linked-EHR), and agreement was fairly good (>80%) except for the main and treatment specialties (57% and 54% respectively) and the patient category (55%). Optional, organism-specific data-fields were less complete, by both methods. Where comparisons were possible, agreement was reasonably high (mostly 70-90%). CONCLUSION:Basic factual information, such as demographic data, is almost-certainly better automated, and many other data fields can potentially be populated successfully from linked-EHR. Manual data collection is time-consuming and inefficient; automated electronic data collection would leave healthcare professionals free to focus on clinical rather than administrative work.
Published: 2018
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23. Developing an antimicrobial resistance reference laboratory and surveillance programme in Vietnam

Author: Nguyen Van Kinh, Heiman F L Wertheim, Guy E Thwaite, Luong Ngoc Khue, Cao Hung Thai, Nguyen Trong Khoa, Ngo thi Bich Ha, Nguyen Vu Trung, Derrick Crook, and H Rogier van Doorn
Subjects: Public aspects of medicine, RA1-1270
Published: 2017
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24. Towards Point-of-Care Diagnosis of Pulmonary Tuberculosis and Drug Susceptibility Testing by Whole Genome Sequencing of DNA Isolated from Sputum

Author: Kayzad S. Nilgiriwala, Louise Pankhurst, Ali Vaughan, Zamin Iqbal, Derrick Crook, Anirvan Chatterjee, and Nerges Mistry
Subjects: Biotechnology, TP248.13-248.65
Abstract: Preliminary screening of pulmonary tuberculosis (TB) in India still relies on sputum microscopy, which has low sensitivity leading to high rate of false negatives. Moreover, conventional phenotypic drug susceptibility testing (DST) is conducted over a period of weeks leading to delays in correct treatment. Next generation sequencing technologies (Illumina and Oxford Nanopore) have made it possible to sequence miniscule amount of DNA and generate enough data within a day for detecting specific microbes and their DST profile. Sputum samples from two pulmonary TB patients were processed by decontamination and DNA was isolated from the decontaminated sputum sediments. The isolated DNA was used for sequencing by Illumina and by MinION (Oxford Nanopore Technologies). The sequence data was used to diagnose TB and to determine the DST profiles for the first- and second-line drugs by Mykrobe Predictor. Validation was conducted by sequencing DNA (by Illumina) isolated from pure growth culture from both the samples individually. DNA sequencing data (for both, Ilumina and MinION) from one of the sputum samples indicated the presence of Mycobacterium tuberculosis (M. tb) resistant to streptomycin, isoniazid, rifampicin and ethambutol and its lineage was predicted to be Beijing East Asia. The second sample indicated the presence of M. tb sensitive to the first- and second-line drugs by MinION and showed minor resistance call only to rifampicin by Illumina. Lineage of the second sample was predicted to be East Africa Indian Ocean, whereas Illumina data indicated it to be Delhi Central Asia. The two samples were correctly diagnosed for the presence of M. tb in the sputum DNA. Their DST profiles and lineage were also successfully determined from both the sequencing platforms (with minor discrepancies) paving the way towards diagnosis and DST of TB from DNA isolated from sputum samples at point-of-care. Nanopore sequencing currently requires skilled personnel for DNA processing and is a costly method – these drawbacks need to be addressed for successful implementation of Nanopore as a point-of-care diagnostic method in future.
Published: 2017
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25. Mycobacterium chimaera Isolates from Heater–Cooler Units, United Kingdom

Author: Jessica Hedge, Theresa Lamagni, Ginny Moore, James Walker, Derrick Crook, and Meera Chand
Subjects: tuberculosis and other mycobacteria, nontuberculous mycobacteria, equipment contamination, heater–cooler units, disease outbreaks, cross-infection, Medicine, Infectious and parasitic diseases, RC109-216
Published: 2017
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26. Evaluation of a cluster-randomized controlled trial of a package of community-based maternal and newborn interventions in Mirzapur, Bangladesh.

Author: Gary L Darmstadt, Yoonjoung Choi, Shams E Arifeen, Sanwarul Bari, Syed M Rahman, Ishtiaq Mannan, Habibur Rahman Seraji, Peter J Winch, Samir K Saha, A S M Nawshad Uddin Ahmed, Saifuddin Ahmed, Nazma Begum, Anne C C Lee, Robert E Black, Mathuram Santosham, Derrick Crook, Abdullah H Baqui, and Bangladesh Projahnmo-2 Mirzapur Study Group
Subjects: Medicine, Science
Abstract: BackgroundTo evaluate a delivery strategy for newborn interventions in rural Bangladesh.MethodsA cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality.FindingsA total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80-1.30) at baseline and 0.87 (95% CI: 0.68-1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported.ConclusionLack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management.Trial registrationClinicaltrials.gov NCT00198627.
Published: 2010
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27. Identification of serotype in culture negative pneumococcal meningitis using sequential multiplex PCR: implication for surveillance and vaccine design.

Author: Samir K Saha, Gary L Darmstadt, Abdullah H Baqui, Belal Hossain, Maksuda Islam, Dona Foster, Hassan Al-Emran, Aliya Naheed, Shams El Arifeen, Stephen P Luby, Mathuram Santosham, and Derrick Crook
Subjects: Medicine, Science
Abstract: PCR-based serotyping of Streptococcus pneumoniae has been proposed as a simpler approach than conventional methods, but has not been applied to strains in Asia where serotypes are diverse and different from other part of the world. Furthermore, PCR has not been used to determine serotype distribution in culture-negative meningitis cases.Thirty six serotype-specific primers, 7 newly designed and 29 previously published, were arranged in 7 multiplex PCR sets, each in new hierarchies designed for overall serotype distribution in Bangladesh, and specifically for meningitis and non-meningitis isolates. Culture-negative CSF specimens were then tested directly for serotype-specific sequences using the meningitis-specific set of primers. PCR-based serotyping of 367 strains of 56 known serotypes showed 100% concordance with quellung reaction test. The first 7 multiplex reactions revealed the serotype of 40% of all, and 31% and 48% non-meningitis and meningitis isolates, respectively. By redesigning the multiplex scheme specifically for non-meningitis or meningitis, the quellung reaction of 43% and 48% of respective isolates could be identified. Direct examination of 127 culture-negative CSF specimens, using the meningitis-specific set of primers, yielded serotype for 51 additional cases.This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics.
Published: 2008
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28. Exploring the extent of uncatalogued genetic variation in antimicrobial resistance gene families inEscherichia coli

Author: Samuel Lipworth, Derrick Crook, A. Sarah Walker, Tim Peto, and Nicole Stoesser
Abstract: BackgroundAntimicrobial resistance (AMR) inE. coliis a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to a variants in a curated reference database with an implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study we evaluated the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility-phenotype prediction inE. coli.MethodsWe assembled a global dataset of 9001E. colisequences of which 8586 had linked antibiotic susceptibility data. Raw reads were assembled using Shovill and AMR genes extracted using the NCBI AMRFinder tool. Mash was used to calculate the similarity between extracted genes using Jaccard distances. We empirically reclustered extracted gene sequences into AMR-associated gene families (70% match) and alleles (ARGs, 100% match).ResultsThe performance of the AMRFinder database for genotype-to-phenotype predictions using strict 100% identity and coverage thresholds did not meet FDA thresholds for any of the eight antibiotics evaluated. Relaxing filters to default settings improved sensitivity with a specificity cost. For all antibiotics, a small number of genes explained most resistance although a proportion could not be explained by known ARGs; this ranged from 75.1% for co-amoxiclav to 3.4% for ciprofloxacin. Only 17,177/36,637 (47%) of ARGs detected had a 100% identity and coverage match in the AMRFinder database. After empirically reclassifying genes at 100% nucleotide sequence identity, we identified 1292 unique ARGs of which 158 (12%) were present ≥10 times, 374 (29%) were present 2-9 times and 760 (59%) only once. Simulated accumulation curves revealed that discovery of new (100%-match) ARGs present more than once in the dataset plateaued relatively quickly whereas new singleton ARGs were discovered even after many thousands of isolates had been included. We identified a strong correlation (Spearman coefficient 0.76 (95% CI 0.72-0.79, pblaTEM-1, we demonstrated that uncatalogued variation, including synonymous variation, is associated with potentially important phenotypic differences (e.g. two common, uncataloguedblaTEM-1alleles with only synonymous mutations compared to the known reference were associated with reduced resistance to co-amoxiclav [aOR 0.57, 95%CI 0.34-0.93, p=0.03] and piperacillin-tazobactam [aOR 0.54, 95%CI 0.32-0.87, p=0.01]).ConclusionsOverall we highlight substantial uncatalogued genetic variation with respect to known ARGs, although a relatively small proportion of these alleles are repeatedly observed in a large international dataset suggesting strong selection pressures. The current approach of using fuzzy matching for ARG detection, ignoring the unknown effects of uncatalogued variation, is unlikely to be acceptable for future clinical deployment. The association of synonymous mutations with potentially important phenotypic differences suggests that relying solely on amino acid-based gene detection to predict resistance is unlikely to be sufficient. Finally, the inability to explain all resistance using existing knowledge highlights the importance of new target gene discovery.
Published: 2023
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29. Evaluation of nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis

Author: Michael B Hall, Marie Sylvianne Rabodoarivelo, Anastasia Koch, Anzaan Dippenaar, Sophie George, Melanie Grobbelaar, Robin Warren, Timothy M Walker, Helen Cox, Sebastien Gagneux, Derrick Crook, Tim Peto, Niaina Rakotosamimanana, Simon Grandjean Lapierre, and Zamin Iqbal
Subjects: Microbiology (medical), Infectious Diseases, Virology, Microbiology
Abstract: BACKGROUND: Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis. METHODS: In this genomic analysis, we analysed 151 M tuberculosis isolates from Madagascar, South Africa, and England, which were collected between 2011 and 2018, using phenotypic DST and matched Illumina and Nanopore data. Illumina sequencing was done with the MiSeq, HiSeq 2500, or NextSeq500 platforms and Nanopore sequencing was done on the MinION or GridION platforms. Using highly reliable PacBio sequencing assemblies and pairwise distance correlation between Nanopore and Illumina data, we optimise Nanopore variant filters for detecting single-nucleotide polymorphisms (SNPs; using BCFtools software). We then used those SNPs to compare transmission clusters identified by Nanopore with the currently used UK Health Security Agency Illumina pipeline (COMPASS). We compared Illumina and Nanopore WGS-based DST predictions using the Mykrobe software and mutation catalogue. FINDINGS: The Nanopore BCFtools pipeline identified SNPs with a median precision of 99.3% (IQR 99.1-99.6) and recall of 90.2% (88.1-94.2) compared with a precision of 99.6% (99.4-99.7) and recall of 91.9% (87.6-98.6) using the Illumina COMPASS pipeline. Using a threshold of 12 SNPs for putative transmission clusters, Illumina identified 98 isolates as unrelated and 53 as belonging to 19 distinct clusters (size range 2-7). Nanopore reproduced 15 out of 19 clusters perfectly; two clusters were merged into one cluster, one cluster had a single sample missing, and one cluster had an additional sample adjoined. Illumina-based clusters were also closely replicated using a five SNP threshold and clustering accuracy was maintained using mixed Illumina and Nanopore datasets. Genotyping resistance variants with Nanopore was highly concordant with Illumina, having zero discordant SNPs across more than 3000 SNPs and four insertions or deletions (indels), across 60 000 indels. INTERPRETATION: Illumina and Nanopore technologies can be used independently or together by public health laboratories performing M tuberculosis genotypic DST and outbreak investigations. As a result, clinical and public health institutions making decisions on which sequencing technology to adopt for tuberculosis can base the choice on cost (which varies by country), batching, and turnaround time. FUNDING: Academy for Medical Sciences, Oxford Wellcome Institutional Strategic Support Fund, and the Swiss South Africa Joint Research Award (Swiss National Science Foundation and South African National Research Foundation).
Published: 2023
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30. Deep Learning and Single Cell Phenotyping for Rapid Antimicrobial Susceptibility Testing

Author: Aleksander Zagajewski, Piers Turner, Conor Feehily, Hafez El Sayyed, Monique Andersson, Lucinda Barrett, Sarah Oakley, Mathew Stracy, Derrick Crook, Christoffer Nellåker, Nicole Stoesser, and Achillefs N. Kapanidis
Abstract: The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current gold-standard antimicrobial susceptibility tests (ASTs) are low-throughput and can take up to 48 hours, with implications for patient care. We present advances towards a novel, rapid AST, based on the deep-learning of single-cell specific phenotypes directly associated with antimicrobial susceptibility inEscherichia coli. Our models can reliably (80% single-cell accuracy) classify untreated and treated susceptible cells, across a range of antibiotics and phenotypes - including phenotypes not visually distinct to a trained, human observer. Applying models trained on lab-reference susceptible strains to clinical isolates ofE. colitreated with ciprofloxacin, we demonstrate our models reveal significant (p
Published: 2022
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31. Repeated evolution of bedaquiline resistance inMycobacterium tuberculosisis driven by truncation ofmmpR5

Author: Leah W Roberts, Kerri M Malone, Martin Hunt, Lavania Joseph, Penelope Wintringer, Jeff Knaggs, Derrick Crook, Maha R Farhat, Zamin Iqbal, and Shaheed V Omar
Abstract: The antibiotic Bedaquiline (BDQ) is a key component of new WHO regimens for drug resistant tuberculosis (TB) but predicting BDQ resistance (BDQ-R) from genotypes remains challenging. We analysed a collection (n=505) ofMycobacterium tuberculosisfrom two high prevalence areas in South Africa (Cape Town and Johannesburg, 2019-2020), and found 53 independent acquisitions of 31 different mutations within themmpR5regulatory gene, with a particular enrichment of truncated MmpR5 in BDQ-R isolates by either frameshift or introduction of an insertion element. Truncations occurred across threeM. tuberculosislineages, impacting 66% of BDQ-R isolates. Extending our analysis to 1,961 isolates with minimum inhibitory concentrations (MICs) revealed thatmmpR5-disrupted isolates had a median BDQ MIC of 0.25 mg/L, compared to the wild-type median of 0.06 mg/L. By matchingmmpR5-disrupted isolates with phylogenetically close control isolates without the disruption, we were able to estimate the impact on MIC of individual mutations. In conclusion, as the MIC increase borders the ECOFF threshold for BDQ-R, we recommend the continued use of MICs and detection of MmpR5 truncations to identify modest shifts in BDQ-R.
Published: 2022
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32. Omicron-associated changes in SARS-CoV-2 symptoms in the United Kingdom

Author: Karina Doris, Vihta, Koen B, Pouwels, Tim Ea, Peto, Emma, Pritchard, Thomas, House, Ruth, Studley, Emma, Rourke, Duncan, Cook, Ian, Diamond, Derrick, Crook, David A, Clifton, Philippa C, Matthews, Nicole, Stoesser, David W, Eyre, and Ann Sarah, Walker
Subjects: Microbiology (medical), Infectious Diseases, otorhinolaryngologic diseases
Abstract: BackgroundThe SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses.MethodsIn a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in PCR-positive infection episodes vs. PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1 and BA.2 variants were dominant.ResultsBetween October-2020 and April-2022, 120,995 SARS-CoV-2 PCR-positive episodes occurred in 115,886 participants, with 70,683 (58%) reporting symptoms. The comparator comprised 4,766,366 PCR-negative study visits (483,894 participants); 203,422 (4%) reporting symptoms. Symptom reporting in PCR-positives varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, maintained with BA.2 (44%/45% 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negatives. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negatives. Symptoms were consistently more common in adults aged 18-65 years than in children or older adults.ConclusionsIncreases in sore throat (also common in the general community), and a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies.SummaryIn a UK community study, loss of taste/smell was markedly less commonly reported with Omicron BA.1/BA.2 than Delta SARS-CoV-2 infections, with smaller declines in reported shortness of breath, myalgia and fatigue/weakness, but increases in sore throat, challenging symptom-based testing algorithms.
Published: 2022
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33. Antibiotic Review Kit for Hospitals (ARK-Hospital): a stepped wedge cluster randomised controlled trial

Author: Martin J Llewelyn, Eric P Budgell, Magda Laskawiec-Szkonter, Elizabeth LA Cross, Rebecca Alexander, Stuart Bond, Phil Coles, Geraldine Conlon-Bingham, Samantha Dymond, Morgan Evans, Rosemary Fok, Kevin J Frost, Veronica Garcia-Arias, Stephen Glass, Cairine Gormley, Katherine Gray, Clare Hamson, David Harvey, Tim Hills, Shabnam Iyer, Alison Johnson, Nicola Jones, Parmjit Kang, Gloria Kiapi, Damien Mack, Charlotte Makanga, Damian Mawer, Bernie McCullagh, Mariyam Mirfenderesky, Ruth McEwen, Sath Nag, Aaron Nagar, John Northfield, Jean O’Driscoll, Amanda Pegden, Robert Porter, Neil Powell, David Price, Elizabeth Sheridan, Mandy Slatter, Bruce Stewart, Cassandra Watson, Immo Weichert, Katy Sivyer, Sarah Wordsworth, Jack Quaddy, Marta Santillo, Adele Krusche, Laurence SJ Roope, Fiona Mowbray, Kieran S Hand, Melissa Dobson, Derrick Crook, Louella Vaughan, Susan Hopkins, Lucy Yardley, Timothy EA Peto, and Ann Sarah Walker
Abstract: BackgroundStrategies to reduce antibiotic overuse in hospitals depend on clinicians taking decisions to stop unnecessary antibiotics. There is a lack of evidence on how support clinicians do this effectively. We evaluated a multifaceted behaviour change intervention (ARK) which aims to reduce antibiotic consumption in hospitals by increasing decisions to stop antibiotics at clinical review.MethodsWe performed a stepped-wedge, hospital-level, cluster-randomised controlled trial using computer-generated sequence randomisation of 39 acute hospitals to 7 calendar-time blocks (12/February/2018–01/July/2019). Co-primary outcomes were monthly antibiotic defined-daily-doses (DDD) per acute/medical admission (organisation-level, superiority) and all-cause 30-day mortality (patient-level, non-inferiority, margin 5%). Clusters were eligible if they admitted non-elective medical patients, could identify an intervention “champion” and provide pre-intervention data from February/2016. Sites were followed up for a minimum of 14 months. Intervention effects were assessed using interrupted time series analyses in each cluster. Overall effects were derived through random-effects meta-analysis, using meta-regression to assess heterogeneity in effects across prespecified factors. Trial registration was ISRCTN12674243.FindingsAdjusted estimates showed a year-on-year reduction in antibiotic consumption (−4.8%, 95%CI: -9.1%,-0.2%, p=0.042) following the ARK intervention. Among 7,160,421 acute/medical admissions, we observed a -2.7% (95%CI: -5.7%,+0.3%, p=0.079) immediate and +3.0% (95%CI: - 0.1%,+6.2%, p=0.060) sustained change in adjusted 30-day mortality. This mortality trend was not related to the magnitude of antibiotic reduction achieved (Spearman’s ρ=0.011, p=0.949). Whilst 90-day mortality odds appeared to increase over time (+3.9%, 95%CI:+0.5%,+7.4%, p=0.023), this was not observed among admissions before COVID-19 onset (+3.2%, 95%CI:-1.5%,+8.2%, p=0.182). Length of hospital stay was unaffected.InterpretationThe weak, inconsistent effects of the intervention on mortality are likely to be explained by the COVID-19 pandemic onset during the post-implementation phase. We conclude that the ARK-intervention resulted in sustained, safe reductions in hospital antibiotic use.FundingNIHR Programme Grants for Applied Research, RP-PG-0514-20015.Research in contextEvidence before this studyAcutely ill patients often need to receive antibiotics before full diagnostic information is available. Consequently, reducing overuse of antibiotics in hospitals requires clinicians to review and where appropriate, stop unnecessary antibiotic prescriptions. Evidence-based tools to support clinicians stop unnecessary antibiotics do not exist.We searched PubMed, with no language or date restrictions, on 31/January/2022 for clinical studies focused on improving antibiotic use for hospitalised adults using the terms “anti-bacterial agents therapeutic use” AND “antibiotic stewardship”. Among the 427 studies found, the great majority were uncontrolled evaluations of different approaches to education, decision support and feedback. These included one before-after study, which found no impact of unsupported clinician-led prescription review. Three small, hospital-level cluster-randomised trials were identified. One evaluated different approaches to feedback, one compared different hospital specialties and one found intense feedback to be effective. All were small and none considered clinical outcomes or sustainability. There is a need for research to deliver proven interventions ready for implementation into practice.Added value of this studyWe evaluated a multifaceted “Antibiotic Review Kit” (ARK) intervention to support prescribers to appropriately stop antibiotics at clinical review. ARK comprises a prescription decision-aid supported by a brief online training tool, guidance on implementation (including regular data collection and feedback) and a patient information leaflet. We found that the intervention was associated with a sustained reduction in hospital-level antibiotic use overall and of oral and narrow-spectrum antibiotics specifically. Weak trends were observed for 30-day mortality in opposite directions for immediate and sustained impact. Although there was a sustained increase in 90-day mortality after the intervention, this was only seen when analyses included patients admitted after the start of the COVID-19 pandemic. Taken together we conclude that these mortality effects are unrelated to the intervention.Implications of all available evidenceThe ARK intervention is safe and effective in reducing antibiotic use among adult medical hospital admissions. The tools used are now freely available for adoption into practice.
Published: 2022
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34. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, David Abdo, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Amina Abdulle, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul Amna Abeer Ul Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Sara Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Lisa Adams, Richard Adams, Tim Adams, Kirsty Adcock, Jemaimah Addai, Ade Adebiyi, Ken Adegoke, Vicki Adell, Debo Ademokun, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Dominic Affron, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Penny Agent, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Humayun Ahmad, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Iram Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Sophia Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Giulia Airoldi, Myriam Aissa, Lindianne Aitken, Bini Ajay, Francis Ajeneye, Abdulakeem Ajibode, Ayesha Ajmi, Tahir Akbar, Naim Akhtar, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olajide Akinwumiju, Olugbenro Aktinade, Ahmad Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Karina Al-Asadi, Kyriaki Alatzoglou, Manaf Al-Bayati, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Charlotte Alford, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Hoodo Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sabira Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Allameddine Allameddine, Fiona Allan, Rachel Allan, Alison Allanson, Robert Allcock, Beverley Allen, Eireann Allen, Jess Allen, Kerry Allen, Laura Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Balaal Alyas, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Kenneth Amenyah, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Mariam Ammoun, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Rekha Anand, Samantha Anandappa, Julie Anderson, Kevin Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Susan Andrews, Gregory Andrikopoulos, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, George Apostolides, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Emily Arbon, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Sylvia Armstrong-Fisher, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Sarah Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Andrea Arroyo, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Glen Ashby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Deborah Asher, 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Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Sibel Bafekr Mishamandani, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Stephen Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Sanchia Baines, Vikram Bains, Aimi Baird, David Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Charles Baker, Emma Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Nauman Bakhtiar, Panos Bakoulas, Julie Balaam, Niranjan Balachandran, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Rebekah Baldwin-Jones, James Balfour, Gagan Bali, Sonya Balkee, Ceri Ball, Kasia Ballard, Amy Ballinger, Ismael Balluz, Craig Balmforth, Emese Balogh, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Tanya Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Millie Banerjee, Ritwik Banerjee, Harrison Banks, Lauren Banks, Luke Banks, Paul Banks, Oliver Bannister, Bharat Bansal, Robert Banthorpe, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya Mouli Baral, Desislava Baramova, Alex Barber, Russel Barber, Emma Barbon, Miriam Barbosa, Monica Barbosa, Jamie Barbour, Alexander Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Helen Barker, Joseph Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Matthew Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Joe Barry, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Ayten Basoglu, Gilda Bass, John Bassett, G Bassett, Chris Bassford, Pavinder Bassi, Betsy Bassis, Bengisu Bassoy, Victoria Bastion, Anupam Basumatary, Tristan Bate, Harry J Bateman, Ian Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Donna Batty, Harry Batty, Thomas Batty, Peter Baughan, Miranda Baum, Carina Bautista, Fareha Bawa, Fatima S Bawani, Simon Bax, Lydia Baxter, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Charlotte Baylem, Lee Bayliss, Eileen Bays, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Philip Beak, Andy Beale, Kirk Beard, Jack Bearpark, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Gail Beech, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Jasmine Beharry, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gill Bell, Gillian Bell, Joshua Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer L Bell, Jennifer Bellamu, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Alexander Bennett, Ann Bennett, Caroline Bennett, Christopher Bennett, Gillian Bennett, Ian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Karen Bennion, Vivienne Benson, Jane Benstead, Andrew Bentley, Dionne Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Marnie Berwick, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Sangam Bhandari, Aashutosh Bhanot, Ravina Bhanot, Sruti Bhaskara, Prashanth Bhat, Nikhil Bhatia, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Carron Bilton, Teodirico Binas, Martin Binney, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Jenny Birch, Louann Birch, Janet Birchall, Katherine Birchall, Sam Bird, Sumedha Bird, Charndip Biring, Mark Birt, Raquel Bisa, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Stuart Blackmore, Caroline Blackstock, Loraine Blackwood, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Mary Blanton, Parry Blaxill, Jenny Blaxland, Katie Blaylock, Jane Blazeby, Carol Blears, Natalie Blencowe, Donna Blofield, Ben Bloom, Jack Bloomfield, Angela Bloss, Hannah Bloxham, Louise Blundell, Andrew Blunsum, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Marilyn Boampoaa, Boniface Bobie, Karen Bobruk, Pritesh Bodalia, Neena Bodasing, Tanya Bodenham, Sherin Bodh, Gabriele Boehmer, Marta Boffito, Kristyna Bohmova, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed Owais Bokhari, Ambrose Boles, Sarah Bollington, Sam Bolton, Charlotte Bomken, Charlotte Bond, Hayley Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Wendy Bonnert, Lizzy Bonney, Leigh Boorman, Catherine Booth, Joanne Borbone, Cameron Borhani, Naomi Borman, Rachel Borrell, Mamu Boshir, Fiona Bottrill, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Darren Bowen, Kaye Bowen, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Geoff Bowyer, Helen Bowyer, Carmel Boyd, Jenny Boyd, Laura Boyd, Maxine Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Osman Bozdag, Leanna Brace, David Brack, Charlotte Brackstone, Rob Bradburn, Jodie Bradder, Barry Bradley, Clare Jane Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Sarah 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Nathaniel Broughton, Matt Brouns, Marie Browett, Alison Brown, Ammani Brown, Carly Brown, Catrin Brown, Chloe Brown, Elizabeth Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Rachel Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Wayne Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, David Bruce, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Alan Brunton, Margaret Brunton, Mandy Bryan, Meera Bryant, April Buazon, Maya Buch, Julie Buchan, Ruaridh Buchan, Alexis Buchanan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Matthew Buckland, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, Kathleen Buckmire, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, 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Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Ana Canabarro, Lisa Canclini, Shaula Mae Candido, Janie Candlish, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Anne Capps-Jenner, Thomas Capstick, Ishmael Carboo, Nuria Cardenas, Mary Cardwell, Rachel Carey, Simon Carley, Tammy Carlin, Andrew Carlton, Samantha Carmichael, Mandy Carnahan, Rebecca Carnegie, Charlotte Caroline, Emily Carpenter, Jodi Carpenter, David Carr, Sharon Carr, Anna Carrasco, Samantha Carrington, Zoe Carrington, Paul Carroll, Caroline Carron, Anne Carstairs, Jonathan Carter, Michael Carter, Moira Carter, Paul Carter, Penny Carter, Steven Carter, Simon Carter-Graham, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Sinead Carty, Jaime Carungcong, Carolyn Carveth-Marshall, Susan Casey, Annie Cassells, Barbara Cassimon, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Matthew Caudwell, Jill Caulfield, Anna Cavazza, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin Hui Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Vikki Chandler-Vizard, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Cherry Chang, Yvonne Chang, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Linda Chapple, Amanda Charalambou, Bethan Charles, Dianne Charlton, Sally Charlton, Kevin Chatar, Calvin Chatha, Ritesh Chaube, Muhammad YN Chaudhary, Iram Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi S Chauhan, Vipul Chauhan, Nicola Chavasse, Iknam Chaven, Rosanna Chavez, Vipal Chawla, Maria Cheadle, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Suzanne Cherif, Mary Cherrie, Helen Cheshire, Barry Chesterson, Betty Cheung, Chee Kay Cheung, Elaine Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Zviedzo A Chikwanha, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Karen Chinn, Vashira Chiroma, Heather Chisem, Claire Chisenga, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Vandana Choudhary, Sarah Choudhury, Bing-Lun Chow, Fateha Chowdhury, Mahibbur Chowdhury, Shahid Chowdhury, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Shabs Chucha, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Y Chung, Ben Church, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Nick Ciccone, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Felicity Clark, Gabrielle Clark, James Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Matthew Clark, Patricia Clark, Richard Clark, Thomas Clark, Wendy Clark, Zoe Clark, Andrea Clarke, Heather Clarke, Mark Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sarah Clarke, Sheron Clarke, Tracy Clarke, Andrew Clarkson, Alleyna Claxton, Kate Clay, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Francesca Clemons, Lee Clifford, Lynne Clifford, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Tony Coates, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Carol Cole, Esther Cole, Jade Cole, Joby Cole, Julie Cole, Richard Cole, Sue Cole, Garry Coleman, Matt Coleman, Holly Coles, Rebecca Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Dawn Collier, Heather Collier, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Ryan Colwell, Edward Combes, David Comer, Alison Comerford, Mike Comery, Dónal Concannon, Robin Condliffe, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Mireille Connolly, Emma Connor, Samantha Conran, Antonia Conroy, Veronica Conteh, Rory Convery, Camilla Conway, Francesca Conway, Grainne Conway, Rhiannon Conway, Jo-Anna Conyngham, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Danielle Cooke, Graham Cooke, Katrina Cooke, Soo Cooke, Tim Cooke, Adele Cooper, Alison Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Joanne Cooper, Joshua Cooper, Laura Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Emma Cooperwaite, Thomas Cope, Sinead Corbet, Carolyn Corbett, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Mirella Corredera, Ruth Corrigan, Catherine Corry, Rita Corser, Denise Cosgrove, Tracey Cosier, Patricia Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Alice Cotton, Caroline Cotton, Katy Cotton, Andrew Coull, James Coulson, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Alexander Cowan, Elena Cowan, Ruth Cowburn, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Debra Anne Cox, Ellie Cox, Giles Cox, Karina Cox, Miriam Cox, Karen Coy, Beverly Craig, Victoria Craig, Felicity Craighead, Matthew Cramp, Beverley Crane, Jacolene Crause, Adrian Crawford, Angie Crawford, Emma Crawford, Isobel Crawford, Richard Crawforth, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Ryan Creighton, Joanne Cremona, Saveria Cremona, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Ian Cron, Derrick Crook, Jennifer Crooks, Helen Croot, Harriet Crosby, Sarah Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Helen Crumley, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Donna Cullen, Lorraine Cullen, Gillian Cummings-Fosong, Marie Cundall, Victoria Cunliffe, Lorraine Cunningham, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Debra Curley, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Abi Curtis, Becca Curtis, Jonathan Curtis, Katrina Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Sean Cutler, Marta Czekaj, Patrycja Czylok, Joana da Rocha, Andrew Dagens, Helen Daggett, Phil Daggett, Jacqui Daglish, Sandeep Dahiya, Helen Dakers-Black, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Jolyon Dales, Helen Dalgleish, Nikki Dallas, Helen Dallow, Dermot Dalton, Zoe Daly, Akila Danga, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Sandra Danso-Bamfo, Nimo Daoud, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Tace Darling, Kate Darlington, Tom Darton, Guledew Darylile, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Emily Davenport, Mark Davey, Michelle Davey, Miriam Davey, Molly Davey, Arlene David, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Alison Davies, Amanda Davies, Amy Davies, Angela Davies, Carolyn Davies, Catrin Davies, Cheryl Davies, Drew Davies, Elaine Davies, Ffyon Davies, Helen Davies, James Davies, Jane Davies, Jeni Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa Davies, Mark Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Alison Davis, Gwyneth Davis, Illinos Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Alexander Davison, Sophia Davison, Mark Davy, Christine Dawe, H Dawe, Mark Dawkins, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Susan Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Helena Day, Jacob Day, Jeremy Day, Lynn Day, Jamie D'Costa, Parijat De, Duneesha de Fonseka, Toni de Freitas, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Anthony de Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Alison Deary, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Raji Dehulia, Max Deighton, Manuela Del Forno, Arnold Dela Rosa, Lisa Delaney, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Randle Derbyshire, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Brendan Devine, Sirjana Devkota, Nicola Dewland, Prakash Dey, Vishal Dey, Rogin Deylami, Jazz Dhaliwal, Kevin Dhaliwal, Jas Dhalliwal, Mandeep Dhanda, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Devesh Dhasmana, Aman Dhesi, Ekanjali Dhillon, Reiss Dhillon, Pamela Diamond, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Debbie Dickerson, Pamela Dicks, Stuart Dickson, Julie Dijo, Sean Dillane, Sarah Diment, Paul Dimitri, Maria Dineen, ThaiHa Dinh, Tri Dinh, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Caroline Dixon, Giles Dixon, Stephen Dixon-Mould, Brice Djeugam, Petr Dlouhy, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Joanne Donnachie, Christopher Donnelly, Eilish Donnelly, Ronan Donnelly, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Sinead Donton, Emma Dooks, Grainne Doran, Kane Dorey, Sharon Dorgan, Amanda Dornan, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Katie Douglas, Jonathan Douse, Lucy Dowden, Michelle Dower, Kerry Dowling, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Philippa Downey, Robert Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragomir, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Nikki Drogman, Graham Drummond, Ronald Druyeh, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Ophias Dube, Stephen Duberley, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Sam Duff-Miller, Helen Duffy, Lionel Dufour, Annette Duggan, Helen Duggan, Parveen Dugh, Janice Duignan, Mick Duley, Simon Dummer, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, Stephanie Dundas, Alessia Dunn, Charlotte Dunn, Damian Dunn, Laura Dunn, Paul Dunn, Charlene Dunne, Karen Dunne, Fiona Dunning, Aidan Dunphy, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Steve Durgacharan, Natalie Duric, Alison Durie, Emily Durie, Hannah Durrington, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Lee Dyble, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Laura 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Elliott, Toby Elliott, Annie Ellis, Ann-Marie Ellis, Christine Ellis, Kay Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Megan Ellison, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed Elmi, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Robert Elshaw, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Helen Escreet, Peter Eskander, Hanif Esmail, Lise Estcourt, Amy Evans, Brynach Evans, Chris Evans, Daren Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lisa Evans, Lynn Evans, Margaret Evans, Michelle Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Ryan Evans, Teriann Evans, Terry John Evans, Tony Eve, Caroline Everden, Serenydd Everden, Hayley Evison, Lynsey Evison, Penny Eyton-Jones, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, Jonathan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Qayyum Farah, Novin Fard, Amr Farg, Margaret Farinto, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Karen Farrar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Maria Faulkner, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Kelly Feane, Simon Fearby, Alex Feben, Federico Fedel, Daria Fedorova, James Feely-Henderson, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Stephanie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Callum Jeevan Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari Gersogamo, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Len Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Sarah Finbow, Debbie Finch, Joanne Finch, Laurie Finch, Joanne Finden, Natalie Fineman, Lauren Finlayson, Adam Finn, Joanne Finn, Clare Finney, Sofia Fiouni, Jo Fiquet, Dani Fisher, Emily Fisher, James Fisher, Neil Fisher, Meadow Fisher Crisp, Daniel Fishman, Krystofer Fishwick, Lorraine Fitzgerald, Chloe Fitzpatrick-Creamer, Jan Flaherty, Michael Flanagan, Charles Flanders, Cathy Flatters, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Karen Flewitt, Christopher Flood, Ian Floodgate, Vincent Florence, Sharon Floyd, Kelly Flynn, Rachel Flynn, Sara Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Claire Foley, Paul Foley, Linda Folkes, Daniela Mock Font, Evodian Fonyonga, Aiwyne Foo, Jane Foo, Andrew Foot, Jayne Foot, Jane Forbes, Jamie Ford, Kathy Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Theodora Foukanelli, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Daniel Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Yasin Fozdar, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Jason Frankcam, Helen Frankland, Gayle Franklin, Jessica Franklin, Darron Franks, Catherine Fraser, Laura Fraser, Sharon Frayling, Martyn Fredlund, Matthew Free, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Ian Freestone, Eleanor French, Matthew Frise, Renate Fromson, Claire Froneman, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Jake Fryer, Janet Fu, Bridget Fuller, Liz Fuller, Neil Fuller, Tracy Fuller, Duncan Fullerton, Jenny Fullthorpe, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Charlene Furtado, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Diana Gabriel, Hadiza Gachi, Rose Gad, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Zacharoula Galani, Christopher Gale, Hugo Gale, Rebecca Gale, Swetha Gali, Karen Galilee, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Jill Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Justin Garner, Lucie Garner, Zoe Garner, Kimberley Garnett, Robert Garney, Rosaline Garr, Michael Garstka, Peter Gartan, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Noha Gasmalseed, Michaela Gaspar, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Alison Geddis, Ian Gedge, Sarah Gee, Minerva Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Susan Gent, Natalie Geoghegan, Chloe George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Hisham Ghanayem, Amardeep Ghattaoraya, Anca Gherman, Alison Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Andrew Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Joanne Gilbert, Kayleigh Gilbert, Sean Gilchrist, Benjamin Giles, Mandy Gill, Rose Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Matt Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Gillian Godding, Emma Godson, Gerry Gogarty, Sukanya Gogoi, Aiky Goh, Rebeca Goiriz, Sriya Gokaraju, Philip Gold, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Bob Goodenough, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Sharif Goolam-Hossen, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Peter Gordon, Sally Gordon, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Diana Gorog, Jan Gorry, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Amanda Gould, Angela Gould, Susan Gould, Lysander Gourbault, Anna Gouveia, Abha Govind, Sharon Gowans, Girish Gowda, Rohit Gowda, Pauline Gowdy, Hannah Gower, Thomas Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Beverley Graham, Clive Graham, Jane Graham, Jonathan Graham, Justin Graham, Libby Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Harriet Gray, Ingrid Gray, Jackie Gray, Karen Gray, Nicola Gray, Sebastian Gray, Alan Grayson, Patricia Grealish, Fiona Greaves, Jack Greaves, Paul Greaves, Charlotte Green, Christopher Green, David Green, Frederick Green, Grace Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Teresa Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Maraneka Greenslade, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, James Gregson, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Amy Gribble, Beverley Grice, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Alexandra Griffiths, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sarah Griffiths, Sharon Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Stephen Grist, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Sharazeq Guettari, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Malin Gunawardena, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Rishi Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Victoria Guratsky, Alvyda Gureviciute, Sambasivarao Gurram, Bhawana Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Berkin Hack, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Nikolaos Hadjisavvas, Leah Hadzik, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Javed Hafsa, Samantha Hagan, Jack W Hague, Rosemary Hague, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Writaja Halder, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Emma Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Bill Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Becky-Lee Halls, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Nicola Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Sara Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, Elizabeth Hampson, Jude Hampson, Lucy Hampson, Ozan Hanci, Ian Hancock, Sadiyah Hand, Jasmine Handford, Soran Handrean, Sarah Haney, Sheharyar Hanif, E Hanison, Alison Hanlon, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Anita Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Helen Hanwell, Mazhar Ul Haq, Ala Haqiqi, Monjurul Haque, Lesley Harden, Zoe Harding, Simon Hardman, Joanna Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, Emily Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Sandra Harlow, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Fiona Harper, Heather Harper, Melanie Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Naomi Harris, Nichola Harris, Sophie Harris, Alex Harrison, David Harrison, Julie Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Heli Harvala, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Sarah Haskins, Zena Haslam, Adil Hassan, Ali Hassan, Wagae UI Hassan, Waqar Ul Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Stephanie Hatch, Jonathan Hatton, Sheryl Haviland, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Annie Hawkins, Catherine Hawkins, Nancy Hawkins, Tanya Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Tamsin Haydon, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Vanessa Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Sarah Haysom, James Hayward, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Gemma Hector, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, Ulla Hemmila, Cassie Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Jennifer Henderson, Steven Henderson, Lee Hennen, Kathryn Hennessy, Natalie Hennesy, Carol Ann Henry, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Mike Herbert, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Emma Heron, Kay Heron, William Herrington, Emilia Heselden, Peta Heslop, Sharnie Beth Hesson, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Jacqueline Hewitson, Claire Hewitt, Davina Hewitt, Richard Hewitt, Robert Heyderman, Nicolette Heydon, Mathis Heydtmann, Joseph Heys, Jonathan Heywood, Gareth Heywood-Beldon, Meg Hibbert, John Hickey, Naomi Hickey, Peter Hickey, Alex Hicks, Jenny Hicks, Rosie Hicks, Scott Rory Hicks, Daniel Higbee, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Alison Hill, Amanda Hill, Helen Hill, Joanne Hill, Lisa Hill, Martin Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Elizabeth Hillerby, Catherine Hillman-Cooper, Elisabeth Hilton, Zoe Hilton, Sarah Hinch, Marcus Hinde, Andrew Hindle, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Alison Hirst, Jemma Hives, Benson Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Renate Hodge, Simon Hodge, Lesley Hodgen, Holly Hodgkins, Louise Hodgkinson, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Catherine Holbrook, Catherine Holden, Melinda Holden, Thomas Holder, Niels Holdhof, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Marie Hollands, Elizabeth Holliday, Nina Holling, Gillian Hollis, Laszlo Hollos, Linda Holloway, Simon Holloway, Marcus Hollyer, Amy Holman, Ann Holmes, Benjamin Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Caroline Holt, Lyndsey Holt, Siobhan Holt, Susie Holt, Alexandra Holyome, Marie Home, Toni Home, Renate Homewood, Kate Hong, Laura Hontoria del Hoyo, Clare Hooper, Sarah Hoosdally, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Zoey Horne, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Nicola Horton-Turner, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Leanne Hostler, Maxine Hough, Sarah Hough, Brittany Houghton, Catherine Houghton, Iain Houghton, Kathryn Houghton, Rebecca Houlihan, Angela Houston, Hamish Houston, Tawedzegwa Hove, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Alison Howarth, Diane Howarth, Serena Howe, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Joanne Hoyle, Josh Hrycaiczuk, Naing Zaya Htoon, Su Htwe, Ying Hu, Chiang Ooi Huah Huah, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Alex Hudson, Cara Hudson, Heather Hudson, Peter Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Eithne Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Laura Humber, Megan Hume, Charlotte Humphrey, Ismay Humphreys, Alasdair Humphries, Joanne Humphries, Lena Hunold, Fiona Hunt, Kristen Hunt, Luke Hunt, Sophie Hunt, Al Hunter, Alexandra Hunter, Isobel Hunter, Karl Hunter, Neil Hunter, George Huntington, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Yusra Husaini, Coralie Huson, Afreen Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Wasim Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Raheem Hussein, Rebecca Hussey, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Mohamed Ibrahim, Monzeer Ibrahim, Wadah Ibrahim, Adetokunbo I Idowu, Muhammad Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Alison Imtiaz, Haider Imtiaz, Claire Ingall, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian P Iordanov, Anil Ipe, Adil Iqbal, Madiha Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Jane Ireland, Robert Irons, Mohannad Irshad, Muhammad S Irshad, Janice Irvine, Val Irvine, Pamela Irving, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Ali Issa, Monica Ivan, Catrina Ivel, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Anthony Jackson, Ben Jackson, Beth Jackson, Douglas Jackson, Ella Jackson, Hayley Jackson, Helen Jackson, Jane Jackson, Julie Jackson, Karin Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Sharon Jackson, Nikita Jacob, Patricia Jacob, Reni Jacob, Nicola Jacques, Terri-Lisa Jacques-Brown, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, Sam Jaggard, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Zeba Jamal, Yasmin Jameel, Albie James, Christie James, Kate James, Lee James, Linda James, Mark James, Nicholas James, Olivia James, Rebecca James, Ruth James, Tracy James, Jack Jameson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Sabrina Jansz, Deepa Japp, Lorraine Jappy, Victor Jardim, Catherine Jardine, Emma Jarnell, Ellie Jarvie, Ann Jarvis, Claire Jarvis, Lisa Jarvis, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Mays Jawad, Lona Jawaheer, Kauky Jawaid, Anu Jayachandran, Dinakaran Jayachandran, Angelina Jayakumar, Deepak Jayaram, Ravi Jayaram, Geeshath Jayasekera, Thilina Jayatilleke, Abi Jayebalan, Saman Jeddi, Vandana Jeebun, Mohammad S Jeelani, Zeynab Jeewa, Emma Jefferson, Katie Jeffery, Helen Jeffrey, Jenni Jeffrey, Rachel Jeffrey, Sue Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, Christopher Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Jacqui Jennings, Louise Jennings, Rebecca Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge Antonio Jesus Silva, Champa Jetha, Kishan Jethwa, Jeby Jeyachandran, Visuvanathan Jeyakumar, Dharshana Jeyapalan, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Navin John, Sarah John, Emma Johns, Margaret Johns, Anne-Marie Johnson, Antoinette Johnson, David Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Tracy Johnson, Zoe Johnson, Claire Johnston, Janet Johnston, Laura Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Hazel Jones, Jac Jones, James Jones, Jamie Jones, Jessica Jones, Jonathon Jones, Julie Jones, Karen Jones, Kate E Jones, Kevin Jones, Laura Jones, Laura M Jones, Lorna Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Annette Jose, Sanal Jose, Anna Joseph, Joseph Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Revati Joshi, Benz Josiah, Tiffany Joyce, Adriel Ju Wen Kwek, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Katarina Kacinova, Nikhil Kadam, Rebecca Kahari, Gail Kakoullis, Azad Kala Bhushan, Richard JK Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Seika Kalsoom, Elisa Kam, John Kamara, Mohamed Kamara, Ajay Kamath, Prakash Kamath, Ravindra Kamath, Siddharth Arun Kamerkar, Nick Kametas, Musaiwale Kamfose, Arul Kandaswamy, Leia Kane, Osei Kankam, Thogulava Kannan, Abhinav Kant, Vikas Kapil, Ritoo Kapoor, Sonal Kapoor, Sourjya Kar, Janaka Kara, Vasita Kara, Marina Karakantza, Rona Kark, Nicholas Karunaratne, Natashja Kasianczuk, Vidya Kasipandian, Rizwan Kassam, Janarth Kathirgamachelvam, Victoria Katsande, Kulbinder Kaul, Daljit Kaur, Dervinder Kaur, Jasmin Kaur, Jaspreet Kaur, Satvinder Kaur, Zunaira Kausar, Mohammad AA Kawser, Andrea Kay, Sarah Kay, Jossy N Kayappurathu, Callum Kaye, Ahemd Kazeem, Naved Kazi, Sharon Kaznica, Samantha Kearley, Rachel Kearns, Nichola Kearsley, Joanne Keating, John Keating, Liza Keating, Elizabeth Keddie-Gray, Katie Keen, Natalie Keenan, Jonathan Kefas, Stephen Kegg, Laura Keith, Uzoamaka Keke, Tosin Kelani, Joanne Kellett, Jeremy Kellington, Alison Kelly, Conor Kelly, David Kelly, Diane Kelly, Dominic Kelly, Emma Kelly, Laura Kelly, Martin Kelly, Michael Kelly, Rosalind Kelly, Sinead Kelly, Stephen Kelly, Thomas Kelly, Mary Kelly-Baxter, Marketa Keltos, Timothy Kemp, Kelly Kemsley, Alexandra Kendall-Smith, Sarah Kennard, Ann Kennedy, Caroline Kennedy, James Kennedy, Sophie Kennedy-Hay, Julia 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Korcierz, James Korolewicz, George Koshy, Chris Kosmidis, Jalpa Kotecha, Easwari Kothandaraman, Leonidas Koukouflis, Koushan Kouranloo, Rukhsana Kousar'c, Margarita Kousteni, Maja Kovac, Alex Kozak Eskenazia, Kestutis Krasauskas, Raghu Krishnamurthy, Vinodh Krishnamurthy, Manju Krishnan, Hari Krishnan, Suzanne Krizak, Sean Krupej, Agnieszka Kubisz-Pudelko, Soren Kudsk-Iversen, Aurimas Kudzinskas, Chirag Kukadiya, Nainesha Kulkarni, Aditi Kumar, Mayur Kumar, Ramesh Kumar, Ravi Kumar, Rita Kumar, Rupa Kumar, Satish Kumar, Vimal Kumar, Arun Kundu, Heinke Kunst, Amit Kurani, Mohammed Kurdy, Rincy Kurian, Vimal Kurmars, Cameron Kuronen-Stewart, Ranganai S Kusangaya, Vlad Kushakovsky, Mandy Kuunal, Apexa Kuverji, Amma Kyei-Mensah, Thyra Kyere-Diabour, Moe Kyi, Nyan M Kyi, Laura Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Emma Laing, Robert Laing, Inez Laing-Faiers, Emily Laity, Michelle Lake, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Nick Lambe, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Abigail Lamikanra, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Rebecca Lanaway, Ivone Lancona-Malcolm, Julia Lancut, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emily Langthorne, Taiya Large, Wojciech Lason, Anna Last, Scott Latham, John Latham-Mollart, Afzal Latheef, Darren Latimer, Nang Latt, Carly-Jane Lattimore, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jennifer Law, Jessica Law, Penny Law, Richard Law, Colin Lawler, Mark Lawley, Emma Lawrence, Jo Lawrence, Neil Lawrence, Ryan Lawrie, Jemima Lawson, Joanne Lawson, Louise Lawson, Rebecca Lawton, Michael Lay, Christine Laycock, Reina Layug, Maria Lazo, Vietland Le, Amelia Lea, William Lea, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna 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Yates, David Yates, Edward Yates, Helen Yates, Julie Yates, Mark Yates, Charlotte Yearwood Martin, Andrew Yeatman, Khin Yein, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Richard Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Raisa Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Lynn Zarb, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Marian Zelman, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Veronica Zindonda, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Roslin Zuha, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Will Zuurbier, Sheba Zyengi, and University of St Andrews. School of Medicine
Subjects: Male, Convalescent plasma, medicine.medical_treatment, 030204 cardiovascular system & hematology, Antibodies, Viral, Rate ratio, 0302 clinical medicine, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Medicine, Hospital Mortality, 030212 general & internal medicine, 11 Medical and Health Sciences, Aged, 80 and over, Medicine(all), Mortality rate, Covid19, Articles, 3rd-DAS, General Medicine, Middle Aged, Hospitals, Treatment Outcome, Female, Open label, Coronavirus Infections, Life Sciences & Biomedicine, RM, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Humans, In patient, Pandemics, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, SARS-CoV-2, business.industry, Significant difference, Immunization, Passive, COVID-19, Length of Stay, NIS, R1, Respiration, Artificial, United Kingdom, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, business
Abstract: Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Published: 2021
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35. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

Author: Daniel Mair, Adrian Signell, Daniel Laydon, Nadua Bayzid, Clare M McCann, Flavia Flaviani, Thomas Connor, Samir Bhatt, Catherine Moore, Dr Benjamin Lindsey, Malte Pinckert, Jane Masoli, Rachel Blacow, Jacqui Prieto, Ian Harrison, Scott Thurston, Lance Turtle, Thushan De Silva, Gregory Young, Natalie Groves, Andrew Nelson, Angie Lackenby, Lily Geidelberg, Mili Estee Torok, Brendan Payne, Katy Gaythorpe, Sonia Goncalves, Ewan Harrison, Andrew Rambaut, Angela Beckett, David Partridge, Swapnil Mishra, Dimitris Grammatopoulos, Judith Breuer, Jenna Nichols, Erik Volz, Sharon Glaysher, Harry David Wilson, Jack Lee, Marta Gallis, Christophe Fraser, Susan Hopkins, Patrick McClure, Derrick Crook, Juan Ledesma, Theocharis Tsoleridis, Natasha Palmalux, Matthew Dorman, Helen Lowe, Kordo Saeed, Oliver Ratmann, Darren Smith, Gilberto Betancor Quintana, Alan McNally, Matthew Bashton, Steven Rudder, Dennis Wang, Joseph Chappell, Elias Allara, Volz, Erik [0000-0001-6268-8937], Mishra, Swapnil [0000-0002-8759-5902], Geidelberg, Lily [0000-0002-8057-1844], Laydon, Daniel J [0000-0003-4270-3321], Jackson, Ben [0000-0002-9981-0649], Gaythorpe, Katy [0000-0003-3734-9081], Kwiatkowski, Dominic P [0000-0002-5023-0176], Flaxman, Seth [0000-0002-2477-4217], Gandy, Axel [0000-0002-6777-0451], Rambaut, Andrew [0000-0003-4337-3707], Ferguson, Neil M [0000-0002-1154-8093], Apollo - University of Cambridge Repository, Medical Research Council, Bill & Melinda Gates Foundation, and Medical Research Council (MRC)
Subjects: The COVID-19 Genomics UK (COG-UK) consortium, Adult, 0301 basic medicine, Time Factors, Adolescent, General Science & Technology, Lineage (evolution), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Basic Reproduction Number, Population genetics, Genome, Viral, Biology, law.invention, Evolution, Molecular, Young Adult, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, law, Phylogenetics, Humans, 030212 general & internal medicine, Child, Phylogeny, Aged, Aged, 80 and over, COVID-19 Genomics UK (COG-UK) consortium, Science & Technology, Multidisciplinary, Generation time, SARS-CoV-2, Infant, Newborn, COVID-19, Infant, Middle Aged, Transmissibility (vibration), 3. Good health, Multidisciplinary Sciences, 030104 developmental biology, Transmission (mechanics), England, Evolutionary biology, Child, Preschool, Spike Glycoprotein, Coronavirus, Science & Technology - Other Topics, Basic reproduction number
Abstract: The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.
Published: 2021
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36. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

Author: Stephanie Hatch, Alexander Mentzer, Aisling M. Curtis, Philippa Matthews, David Eyre, Robert Shaw, Thomas Ritter, Timothy Walker, Gavin Screaton, Ahmed Alhussni, Rebecca Jurdon, Sarah Hoosdally, Nicole Stoesser, Seren Waite, Rebecca Conway-Jones, Greg Howgego, Angus Livingstone, Benjamin Holloway, Koen Pouwels, Matthew Wedlich, Mark Campbell, Laura Wilkins, Afrah Shibu, Liam Peck, Hayleah Pickford, Charlotte Lee, Susan Hopkins, Derrick Crook, Zoe De Toledo, Tariq Ahmed-Firani, Donal Skelly, Joseph Cutteridge, Philip Fowler, Andrey Nezhentsev, Imogen Vorley, Maria Pikoula, Gillian Rodger, and Sheila Lumley
Subjects: Adult, Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Adolescent, Health Personnel, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, Antibodies, Viral, Polymerase Chain Reaction, COVID-19 Serological Testing, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Health care, Epidemiology, Coronavirus Nucleocapsid Proteins, Humans, Medicine, Longitudinal Studies, 030212 general & internal medicine, Seroconversion, Young adult, Aged, Aged, 80 and over, biology, SARS-CoV-2, business.industry, Incidence, Incidence (epidemiology), COVID-19, virus diseases, General Medicine, Middle Aged, United Kingdom, COVID-19 Nucleic Acid Testing, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Female, Original Article, Antibody, business
Abstract: Background The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. Methods We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time. Results A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status. Conclusions The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.)
Published: 2021
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37. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Author: Aekkachai Tuekprakhon, Rungtiwa Nutalai, Aiste Dijokaite-Guraliuc, Daming Zhou, Helen M. Ginn, Muneeswaran Selvaraj, Chang Liu, Alexander J. Mentzer, Piyada Supasa, Helen M.E. Duyvesteyn, Raksha Das, Donal Skelly, Thomas G. Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede Constantinides, Hermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Jiandong Huo, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, and Consortium, OPTIC
Subjects: QR355, South Africa, Neutralization Tests, SARS-CoV-2, COVID-19, Humans, Viral Vaccines, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology
Abstract: The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
Published: 2022

38. Comparison of R9.4.1/Kit10 and R10/Kit12 Oxford Nanopore flowcells and chemistries in bacterial genome reconstruction

Author: Nicholas Sanderson, Natalia Kapel, Gillian Rodger, Hermione Webster, Samuel Lipworth, Teresa street, Tim Peto, Derrick Crook, and Nicole Stoesser
Subjects: General Medicine
Abstract: 2.AbstractComplete, accurate, cost-effective, and high-throughput reconstruction of bacterial genomes for large-scale genomic epidemiological studies is currently only possible with hybrid assembly, combining long- (typically using nanopore sequencing) and short-read (Illumina) datasets. Being able to utilise nanopore-only data would be a significant advance. Oxford Nanopore Technologies (ONT) have recently released a new flowcell (R10.4) and chemistry (Kit12), which reportedly generate per-read accuracies rivalling those of Illumina data. To evaluate this, we sequenced DNA extracts from four commonly studied bacterial pathogens, namely Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus, using Illumina and ONT’s R9.4.1/Kit10, R10.3/Kit12, R10.4/Kit12 flowcells/chemistries. We compared raw read accuracy and assembly accuracy for each modality, considering the impact of different nanopore basecalling models, commonly used assemblers, sequencing depth, and the use of duplex versus simplex reads. “Super accuracy” (sup) basecalled R10.4 reads - in particular duplex reads - have high per-read accuracies and could be used to robustly reconstruct bacterial genomes without the use of Illumina data. However, the per-run yield of duplex reads generated in our hands with standard sequencing protocols was low (typically 3.Impact statementOur understanding of microbes has been greatly enhanced by the capacity to evaluate their genetic make-up using a technology known as whole genome sequencing. Sequencers represent microbial genomes as stretches of shorter sequence known as ‘reads’, which are then assembled using computational algorithms. Different types of sequencing approach have advantages and disadvantages with respect to the accuracy and length of the reads they generate; this in turn affects how reliably genomes can be assembled.Currently, to completely reconstruct bacterial genomes in a high-throughput and cost-effective manner, researchers tend to use two different types of sequencing data, namely Illumina (short-read) and nanopore (long-read) data. Illumina data are highly accurate; nanopore data are much longer, and this combination facilitates accurate and complete bacterial genomes in a so-called “hybrid assembly”. However, new developments in nanopore sequencing have reportedly greatly improved the accuracy of nanopore data, hinting at the possibility of requiring only a single sequencing approach for bacterial genomics.Here we evaluate these improvements in nanopore sequencing in the reconstruction of four bacterial reference strains, where the true sequence is already known. We show that although these improvements are extremely promising, for high-throughput, low-cost complete reconstruction of bacterial genomes hybrid assembly currently remains the optimal approach.4.Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article, through supplementary data files, or in publicly accessible repositories.Nanopore fast5 and fastq data are available in the ENA under project accession: PRJEB51164.Assemblies have been made available at: https://figshare.com/articles/online_resource/q20_comparison_genome_assemblies/196838 67.Code and analysis outputs are available at: https://gitlab.com/ModernisingMedicalMicrobiology/assembly_comparison_analysis/-/tree/main (tagged version v0.5.5).
Published: 2022
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39. The mobilome associated with Gram-negative bloodstream infections: A large-scale observational hybrid sequencing based study

Author: Samuel Lipworth, Willam Matlock, Liam Shaw, Karina-Doris Vihta, Gillian Rodger, Kevin Chau, Leanne Barker, Sophie George, James Kavanagh, Timothy Davies, Alison Vaughan, Monique Andersson, Katie Jeffery, Sarah Oakley, Marcus Morgan, Susan Hopkins, Timothy Peto, Derrick Crook, A. Sarah Walker, and Nicole Stoesser
Abstract: Plasmids carry genes conferring antimicrobial resistance (AMR), and other clinically important traits; their ability to move within and between species may provide the machinery for rapid dissemination of such genes. Existing studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to those carrying particularly antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections (BSI) in 2009 (194 isolates) and 2018 (368 isolates) in Oxfordshire, UK, plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative ‘backbone’ of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.
Published: 2022
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40. The bacteriology of pleural infection using next generation sequencing: The Oxford Pleural Infection Metagenomics Studies (TORPIDS)

Author: Nikolaos I. Kanellakis, John Wrightson, Stephen Gerry, Nicholas Ilott, John Corcoran, Eihab Bedawi, Rachelle Asciak, Andrey Nezhentsev, Anand Sundaralingam, Rob Hallifax, Greta Economides, Lucy Bland, Elizabeth Daly, Xuan Yao, Nick Maskell, Robert Miller, Derrick Crook, Timothy Hinks, Tao Dong, Ioannis Psallidas, and Najib Rahman
Published: 2022
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41. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul-Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Richard Adams, Tim Adams, Krishma Adatia, Kirsty Adcock, Ade Adebiyi, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Binay Adhikari, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olugbenro Aktinade, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Fiona Allan, Alison Allanson, Robert Allcock, Eireann Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Ayesha Ashfaq, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Arshia Aslam, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Brygitta Atraskiewicz, Abdul A Attia, Paula Aubrey, Avinash Aujayeb, Aye CT Aung, Hnin Aung, Kyaw T Aung, Yin Aung, Zaw M Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Gabriel Awadzi, Atia Awan, Aszad Aya, Eman Ayaz, Amanda Ayers, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Nauman Bakhtiar, Panos Bakoulas, Niranjan Balachandran, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Rebekah Baldwin-Jones, James Balfour, Matthew Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Harrison Banks, Luke Banks, Paul Banks, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Desislava Baramova, Russel Barber, Emma Barbon, Miriam Barbosa, Monica Barbosa, Jamie Barbour, Alexander Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Helen Barker, Joseph Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Buddha Basnyat, Ayten Basoglu, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Philip Beak, Andy Beale, Jack Bearpark, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Gail Beech, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer L Bell, Jennifer Bellamu, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Ann Bennett, Caroline Bennett, Gillian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Karen Bennion, Vivienne Benson, Andrew Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Sangam Bhandari, Aashutosh Bhanot, Ravina Bhanot, Prashanth Bhat, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Mark Birt, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Parry Blaxill, Katie Blaylock, Jane Blazeby, Natalie Blencowe, Ben Bloom, Jack Bloomfield, Angela Bloss, Hannah Bloxham, Louise Blundell, Andrew Blunsum, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Marilyn Boampoaa, Boniface Bobie, Karen Bobruk, Pritesh N Bodalia, Neena Bodasing, Tanya Bodenham, Gabriele Boehmer, Marta Boffito, Kristyna Bohmova, Niamh Bohnacker, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed O Bokhari, Ambrose Boles, Charlotte Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Lizzy Bonney, Sarah Boot, Joanne Borbone, Naomi Borman, Mamu Boshir, Fiona Bottrill, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Helen Bowyer, Aileen Boyd, Jenny Boyd, Laura Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Denise Braganza, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Sophie Brattan, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Giovanna Bretland, Chris Brewer, Gavin Bridgwood, Sara Brigham, John Bright, Chris Brightling, Lutece Brimfield, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Mary Brodsky, Fiona Brogan, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity 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Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Richard Burgess, Sophia Burgess, Adrian Burman, Sara Burnard, Caroline Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Daniel Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Matthew Burton, Deborah Butcher, Aaron Butler, Jessica Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Mohammad M Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Amanda Cabandugama, Ruth Cade, Anthony Cadwgan, Ajeng Cahyareny, Donna Cairney, James Calderwood, Darren Caldow, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sarah Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Lisa Canclini, Shaula M Candido, Janie Candlish, Cielito Caneja, Alexandra Cann, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Thomas Capstick, Mary Cardwell, Rachel Carey, Simon Carley, Tammy Carlin, Samantha Carmichael, Mandy Carnahan, Charlotte Caroline, Jodi Carpenter, Sharon Carr, Anna Carrasco, Zoe Carrington, Amy Carroll, Paul Carroll, Jonathan Carter, Michael Carter, Paul Carter, Penny Carter, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Jaime Carungcong, Susan Casey, Annie Cassells, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Matthew Caudwell, Anna Cavazza, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, Bimal Chalise, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin Hui S Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Yvonne Chang, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy C Chappell, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Kevin Chatar, Calvin Chatha, Ritesh Chaube, Muhammad Y N Chaudhary, Iram Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi Singh Chauhan, Nicola Chavasse, Vipal Chawla, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Floria Cheng, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Mary Cherrie, Helen Cheshire, Chee Kay Cheung, Elaine Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Zviedzo A Chikwanha, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Heather Chisem, Claire Chisenga, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Vandana Choudhary, Sarah Choudhury, Bing-Lun Chow, Mahibbur Chowdhury, Shahid Chowdhury, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona 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Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Alison Davis, Gwyneth Davis, Illinos Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Alexander Davison, Christine Dawe, H Dawe, Mark Dawkins, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Susan Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy N Day, Jamie D'Costa, Parijat De, Duneesha de Fonseka, Toni de Freitas, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Anthony De Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Alison Deary, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig 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Elfar, Mayy M Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura N Ellerton, Lucy Elliot, Amy Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Annie Ellis, Christine Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Peter Eskander, Hanif Esmail, Lise Estcourt, Brynach Evans, Chris Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Jolanta Evans, Lisa Evans, Lynn Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Teriann Evans, Terry J Evans, Caroline Everden, Serenydd Everden, Hayley Evison, Lynsey Evison, David Eyre, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Qayyum Farah, Nowin Z Fard, Leila Fares, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Maria Faulkner, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Simon Fearby, Alex Feben, Federico Fedel, Daria Fedorova, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil 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Linda Folkes, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Jayne Foot, Jane Forbes, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Sasha Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Catherine Fraser, Sharon Frayling, Martyn Fredlund, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Bridget Fuller, Liz Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Zoë Gabriel, Hadiza Gachi, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Christopher Gale, Hugo Gale, Rebecca Gale, Swetha Gali, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Justin Garner, Lucie Garner, Zoe Garner, Rosaline Garr, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Ian Gedge, Sarah Gee, Minerva Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Susan Gent, Natalie Geoghegan, Sam George, Tina George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Hisham Ghanayem, Anca Gherman, Alison Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Franciscus Ginting, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Deborah Glowski, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Emma Godson, Sukanya Gogoi, Aiky Goh, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Bob Goodenough, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Sally Gordon, Robin Gore, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Diana Gorog, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Susan Gould, Lysander Gourbault, Abha Govind, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Clive Graham, Jonathan Graham, Justin Graham, Libby Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Jackie Gray, Karen Gray, Nicola Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Charlotte Green, Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sarah Griffiths, Yvonne Griffiths, Sofia 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Fiona McGill, Sarah McGinnity, Hannah McGivern, Neil McGlinchey, Phil McGlone, Deborah McGlynn, Claire McGoldrick, Clare McGoldrick, Elizabeth McGough, Brendan McGrath, Amanda McGregor, Annemarie McGregor, Heather McGuinness, Sean McGuire, Tara McHugh, Caroline McInnes, Neil McInnes, Karen McIntyre, Mhairi McIntyre, Lorna McKay, Conor P McKeag, Madeleine McKee, Joseph McKeever, Shirley McKenna, Donogh McKeogh, Caroline McKerr, Anthony M McKie, Laura Mckie, Gerard McKnight, Heather McLachlan, Andrew McLaren, Barbara McLaren, Nicola McLarty, Maria McLaughlin, James McLay, Mary McLeish, Tina McLennan, Stewart McLure, Anne-Marie McMahon, Genevieve McMahon, Mike McMahon, Stephen McMahon, Terence McManus, Moyra McMaster, Paddy McMaster, Samuel McMeekin, Nicola McMillan, Jason McMinn, Liam McMorrow, Helen McNally, Fiona McNeela, Lynne McNeil, Claire McNeill, Shea McNeill, Una McNelis, Melanie McNulty, Roisin McNulty, Christopher McParland, Mark McPhail, Alison McQueen, Anna McSkeane, Denise 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Abdelrahman Mohamed, Arez Mohamed, Osab Mohamed, Waheed Mohammad, Aliabdulla Mohammed, Omer Mohammed, Yaser N S Mohammed, Bilal A Mohamud, Amr Moharram, Hoi-Ping Mok, Jonathan Mok, Christine Moller-Christensen, Mateus Mollet, Malid Molloholli, Aoife Molloy, Linda Molloy, Andrew Molyneux, Tasnim Momoniat, Holly Monaghan, Krista Monaghan, Shiva Mongolu, Tesha Monika, Katelyn Monsell, Mahmoud Montasser, Alan Montgomery, Hugh Montgomery, Prebashan Moodley, Margaret Moody, Nick Moody, Angela Moon, James Moon, Ji-Hye Moon, Maria Moon, May Moonan, Parvez Moondi, Alex Moore, Christopher Moore, David A J Moore, Faye Moore, Judith Moore, Laura Moore, Sally Moore, Sonia Moore, Rachel Moores, Ed Morab, Jose Morales, Nuria Moramorell, Louise Moran, Grishma Moray, Jeronimo Moreno-Cuesta, Amy Morgan, Caitlin Morgan, Christine Morgan, Colin Morgan, Lauren Morgan, Leila Morgan, Matthew Morgan, Patrick Morgan, Katie Morgan-Jones, Emily Morgan-Smith, Anna Morley, Thomas Morley, Wendy Morley, Anna Morris, 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Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Sri Nallapareddy, Soum Nallapeta, Arumugan Nallasivan, Uttam Nanda, Aarti Nandani, Ali Raza Naqvi, Asadullah Naqvi, Sara Naqvi, Sophia Nasa, Dominic Nash, Nader Nasheed, Abdul Nasimudeen, Umer Nasir, Tahir Nasser, Anuja Natarajan, Geetha Natarajan, Nalin Natarajan, Nikhila Natarajan, Rajkumar Natarajan, Noel Nathaniel, Mala Nathvani, Priyan Nathwani, George Nava, Neena Navaneetham, Jeya Navaratnam, Helen Navarra, Sadaf Naveed, John Navin, Khuteja Nawaz, Sarfaraz Nawaz, Shasta Nawaz, Bonilla Nayar, Suzanne Naylor, Moez Nayyar, Farrah Naz, Mobeena Naz, Babak Nazari, S Nazir, Sehar Nazir, Dumisani Ncomanzi, Onyine Ndefo, Alan Neal, Elaine Neary, Mostafa Negmeldin, Paula Neill, Hector E Neils, Avideah Nejad, Louise Nel, Marie Nelson, Richard Nelson, Scott Nelson, Erni Nelwan, Rajesh Nemane, Samiksha Nepal, Daniel Nethercott, Kimberley Netherton, Kimberley Nettleton, Alison Newby, Angela Newby, David Newby, Tracy Newcombe, Diana Newman, Julie Newman, Oscar Newman, Tabitha Newman, Thomas Newman, Rachel Newport, Maria Newton, Anthony Y K C Ng, Ka Wing Ng, Maxine Ng, Sarah Ng, Wee Jin Ng, Thomas Ngan, Gabriel CE Ngui, Alice Ngumo, Caoimhe Nic Fhogartaigh, Nathalie Nicholas, Philip Nicholas, Donna Nicholls, Lisa Nicholls, Alice Nicholson, Anne Nicholson, Annette Nicholson, Ian Nickson, Eileen Nicol, Elizabeth Nicol, Rebecca Nicol, Pantelis Nicola, Antony Nicoll, Pantzaris Nikolaos, Georgii Nikonovich, Annette Nilsson, Kofi Nimako, Louise Nimako, Camus Nimmo, Preethy Ninan, Mahesh Nirmalan, Muhammad Nisar, Toby Nisbett, Aksinya Nisha James, Sabaahat Nishat, Tomoko Nishiyama, Sara Nix, Jennifer Nixon, Maxine Nixon, Khwaja Nizam Ud Din, Maria Nizami, Lyrics Noba, Harriet Noble, Hsu M Noe, Jerry Nolan, Zahid Noor, Zaid Noori, Louis Norman, Rachel Norman, Karen Norris, Lillian Norris, Sally Ann Nortcliffe, Fiona North, Julie North, Thomas North, John Northfield, Samantha 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Snehal Shah, Suraj Shah, Syed Shah, Wajid Shah, Saarma Shahad, Sousan Shahi, Sipan Shahnazari, Muhammad Shahzeb, Aisha Shaibu, Zara Shaida, Amina Y Shaikh, Maliha Shaikh, Rajit Shail, Mariya Shaji, Muhammad Shakeel, Korah Shalan, Nadia Shamim, Kazi Shams, Thomas Shanahan, Hamed Sharaf, Asir Sharif, Ajay Sharma, Ash Sharma, Bhawna Sharma, Mona Sharma, Ojasvi Sharma, Poonam Sharma, Rajeev Sharma, Sanjeev Sharma, Sarkhara Sharma, Shriv Sharma, Sonal Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Paula Sharratt, Phoebe Sharratt, Katherine Sharrocks, Serene Shashaa, Christopher Shaw, Daisy Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathon Shaw, Lisa Shaw, Tomos G Shaw, Anna Shawcross, Jill Shawe, Lou Shayler, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, Noorann Sheikh, Benjamin Shelley, Sarah Shelton, Anil Shenoy, Julie Shenton, Amy Shepherd, Kate Shepherd, Lorna Shepherd, Scott Shepherd, Rhian Sheppeard, Helen Sheridan, Ray Sheridan, Samuel 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Louise Zammit, Marie Zammit-Mangion, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Sheba Zyengi, Apollo - University of Cambridge Repository, Group, RECOVERY Collaborative, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division
Subjects: Male, Antiviral agents/adverse effects, Drug therapy, combination, Antibodies, Monoclonal, Humanized, Antibodies, Viral, COVID-19/drug therapy, Antiviral Agents, SARS-CoV-2/immunology, SDG 3 - Good Health and Well-being, General & Internal Medicine, Infusions, intravenous, Humans, QR180 Immunology, Treatment outcome, Infusions, Intravenous, 11 Medical and Health Sciences, Aged, MCC, Medicine(all), Aged, 80 and over, SARS-CoV-2, Antibodies, monoclonal, humanized/adverse effects, COVID-19, General Medicine, 3rd-DAS, Antibodies, viral/blood, COVID-19 Drug Treatment, RECOVERY Collaborative Group, Hospitalization, Treatment Outcome, QR180, Drug Therapy, Combination, Female
Abstract: The RECOVERY trial is supported by grants to the University of Oxford (Oxford, UK) from UK Research and Innovation (UKRI; Medical Research Council) and the National Institute of Health Research (NIHR; MC_PC_19056), the Wellcome Trust (222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). Background : Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods : RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings : Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (
Published: 2022
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42. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Author: Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiří Zahradník, Piyada Supasa, Chang Liu, Helen M.E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J.M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra S. Deeks, John Frater, Lisa Frending, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Lucy Rothwell, Lizzie Stafford, J Kenneth Baillie, Peter JM. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christoper A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Shona C. Moore, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L. Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, AA Roger Thompson, Emma C. Thomson, Ryan S. Thwaites, Lance CW. Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Lisa Norman, Riinu Pius, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Sarah McCafferty, Richard Clark, Angie Fawkes, Kirstie Morrice, Alan Maclean, Nicola Wrobel, Lorna Donnelly, Audrey Coutts, Katarzyna Hafezi, Louise MacGillivray, Tammy Gilchrist, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O’Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, UK Research and Innovation, UKRI MRC COVID-19 Rapid Response Call, University of Oxford, Northwestern Polytechnical University (NPU), Charles University [Prague] (CU), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, University of Dayton, Universiteit Gent = Ghent University (UGENT), Computational & Applied Vegetation Ecology (CAVElab), Nanjing University of Science and Technology (NJUST), Weizmann Institute of Science [Rehovot, Israël], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, and Apollo - University of Cambridge Repository
Subjects: variants, receptor interaction, Omicron, SARS-CoV-2, [SDV]Life Sciences [q-bio], OPTIC Consortium, Spike, vaccines, 06 Biological Sciences, Article, General Biochemistry, Genetics and Molecular Biology, RBD, ISARIC4C Consortium, 11 Medical and Health Sciences, immune evasion, Developmental Biology
Abstract: On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses., A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.
Published: 2022
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43. Monitoring populations at increased risk for SARS-CoV-2 infection in the community using population-level demographic and behavioural surveillance

Author: Emma Pritchard, Joel Jones, Karina-Doris Vihta, Nicole Stoesser, Prof Philippa C. Matthews, David W. Eyre, Thomas House, John I Bell, Prof John N Newton, Jeremy Farrar, Prof Derrick Crook, Susan Hopkins, Duncan Cook, Emma Rourke, Ruth Studley, Prof Ian Diamond, Prof Tim Peto, Koen B. Pouwels, Prof A. Sarah Walker, and Team, COVID-19 Infection Survey
Subjects: monitoring, Oncology, SARS-CoV-2, Health Policy, Internal Medicine, community, Public aspects of medicine, RA1-1270, Article
Abstract: Background The COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy. Methods To develop a real-time screening process, we included results from nose and throat swabs and questionnaires taken 19 July 2020-17 July 2021 in the UK's national COVID-19 Infection Survey. Fortnightly, associations between SARS-CoV-2 positivity and 60 demographic and behavioural characteristics were estimated using logistic regression models adjusted for potential confounders, considering multiple testing, collinearity, and reverse causality. Findings Of 4,091,537 RT-PCR results from 482,677 individuals, 29,903 (0·73%) were positive. As positivity rose September-November 2020, rates were independently higher in younger ages, and those living in Northern England, major urban conurbations, more deprived areas, and larger households. Rates were also higher in those returning from abroad, and working in healthcare or outside of home. When positivity peaked December 2020-January 2021 (Alpha), high positivity shifted to southern geographical regions. With national vaccine roll-out from December 2020, positivity reduced in vaccinated individuals. Associations attenuated as rates decreased between February-May 2021. Rising positivity rates in June-July 2021 (Delta) were independently higher in younger, male, and unvaccinated groups. Few factors were consistently associated with positivity. 25/45 (56%) confirmed associations would have been detected later using 28-day rather than 14-day periods. Interpretation Population-level demographic and behavioural surveillance can be a valuable tool in identifying the varying characteristics driving current SARS-CoV-2 positivity, allowing monitoring to inform public health policy. Funding Department of Health and Social Care (UK), Welsh Government, Department of Health (on behalf of the Northern Ireland Government), Scottish Government, National Institute for Health Research.
Published: 2021

44. Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria

Author: Sam Lipworth, Karina-Doris Vihta, Tim Davies, Sarah Wright, Merline Tabirao, Kevin Chau, Alison Vaughan, James Kavanagh, Leanne Barker, Sophie George, Shelley Segal, Stephane Paulus, Lucinda Barrett, Sarah Oakley, Katie Jeffery, Lisa Butcher, Tim Peto, Derrick Crook, Sarah Walker, Seilesh Kadambari, and Nicole Stoesser
Abstract: Background Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population. Methods We perform an epidemiological and sequencing based analysis of Gram-negative bloodstream infections (327 isolates (296 successfully sequenced) from 287 patients) in children Results Here we show that the burden of infection lies predominantly in neonates and that most infections are caused by Escherichia coli, Klebsiella spp. and Enterobacter hormaechei. There is no evidence in our setting that the proportion of antimicrobial resistant isolates is increasing in the paediatric population although we identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of E. coli BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportions of O-antigen serotypes. In most cases in our setting there is no evidence of transmission/point-source acquisition and we demonstrate the utility of whole genome sequencing to refute a previously suspected outbreak. Conclusions Our findings support continued use of current empirical treatment guidelines and suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis.
Published: 2021

45. Genome-wide association studies of global Mycobacterium tuberculosis resistance to thirteen antimicrobials in 10,228 genomes

Author: Zamin Iqbal, Daniel Wilson, Pénélope Wintringer, Kerri M Malone, Derrick Crook, and Samaneh Kouchaki
Subjects: Genetics, Whole genome sequencing, Genome-wide association study, Biology, biology.organism_classification, Genome, Clofazimine, Mycobacterium tuberculosis, chemistry.chemical_compound, Minimum inhibitory concentration, chemistry, 23S ribosomal RNA, Linezolid, medicine, medicine.drug
Abstract: The emergence of drug resistant tuberculosis is a major global public health concern that threatens the ability to control the disease. Whole genome sequencing as a tool to rapidly diagnose resistant infections can transform patient treatment and clinical practice. While resistance mechanisms are well understood for some drugs, there are likely many mechanisms yet to be uncovered, particularly for new and repurposed drugs. We sequenced 10,228 Mycobacterium tuberculosis (MTB) isolates worldwide and determined the minimum inhibitory concentration (MIC) on a grid of twofold concentration dilutions for 13 antimicrobials using quantitative microtiter plate assays. We performed oligopeptide- and oligonucleotide-based genome-wide association studies using linear mixed models to discover resistance-conferring mechanisms not currently catalogued. Use of MIC over binary resistance phenotypes increased heritability for the new and repurposed drugs by 26-37%, increasing our ability to detect novel associations. For all drugs, we discovered uncatalogued variants associated with MIC, including in the Rv1218c promoter binding site of the transcriptional repressor Rv1219c (isoniazid), upstream of the vapBC20 operon that cleaves 23S rRNA (linezolid) and in the region encoding an α-helix lining the active site of Cyp142 (clofazimine, all p-7.7). We observed that artefactual signals of cross resistance could be unravelled based on the relative effect size on MIC. Our study demonstrates the ability of very large-scale studies to substantially improve our knowledge of genetic variants associated with antimicrobial resistance in M. tuberculosis.
Published: 2021
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46. Quantitative drug susceptibility testing for M. tuberculosis using unassembled sequencing data and machine learning

Author: Zamin Iqbal, Daniel Wilson, Kerri M Malone, Derrick Crook, Sarah Earle, Samaneh Kouchaki, Irena Arandjelović, and Michael Inouye
Subjects: Tuberculosis, business.industry, Machine learning, computer.software_genre, medicine.disease, Clofazimine, Multiple drug resistance, chemistry.chemical_compound, chemistry, Linezolid, medicine, Ethionamide, Artificial intelligence, Delamanid, Bedaquiline, business, computer, Ethambutol, medicine.drug
Abstract: There remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs. We trained, validated and tested the system on 10,859 isolates from the CRyPTIC dataset. Essential agreement rates (predicted MIC within one doubling dilution of observed MIC) were above 92% for first-line drugs, 91% for fluoroquinolones and aminoglycosides, and 90% for new and repurposed drugs, albeit with a significant drop in performance for the very few phenotypically resistant isolates in the latter group. To further validate the model in the absence of external MIC datasets, we predicted MIC and converted values to binary for an external set of 15,239 isolates with binary phenotypes, and compare their performance against a previously validated mutation catalogue, the expected performance of existing molecular assays, and World Health Organization Target Product Profiles. The sensitivity of the model on the external dataset was greater than 90% for all drugs except ethionamide, clofazimine and linezolid. Specificity was greater than 95% for all drugs except ethambutol, ethionamide, bedaquiline, delamanid and clofazimine. The proposed system can provide quantitative susceptibility phenotyping to help guide antimicrobial therapy, although further data collection and validation are required before machine learning can be used clinically for all drugs.
Published: 2021
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47. Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

Author: Derrick Crook, Joshua Carter, Samaneh Kouchaki, and Daniel Wilson
Subjects: Whole genome sequencing, Tuberculosis, biology, business.industry, Drug resistance, Computational biology, Molecular diagnostics, biology.organism_classification, medicine.disease, Mycobacterium tuberculosis, Minimum inhibitory concentration, Antibiotic resistance, medicine, Personalized medicine, business
Abstract: The World Health Organization goal of universal drug susceptibility testing for patients with tuberculosis is most likely to be achieved through molecular diagnostics; however, to date these have focused largely on first-line drugs, and always on predicting binary susceptibilities. Here, we used whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration in 15,211 Mycobacterium tuberculosis patient isolates from 27 countries across five continents.This work identifies 449 unique MIC-elevating genetic determinants across thirteen drugs, as well as 91 mutations resulting in hypersensitivity for eleven drugs. Our results provide a guide for further implementation of personalized medicine for the treatment of tuberculosis using genetics-based diagnostics and can serve as a training set for novel approaches to predict drug resistance.
Published: 2021
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48. A data compendium of Mycobacterium tuberculosis antibiotic resistance

Author: Zamin Iqbal, Brice Letcher, Pénélope Wintringer, Kerri M Malone, Derrick Crook, Alice Brankin, and Samaneh Kouchaki
Subjects: Genetics, Tuberculosis, Biology, medicine.disease, biology.organism_classification, Mycobacterium tuberculosis, Clofazimine, chemistry.chemical_compound, Antibiotic resistance, chemistry, Linezolid, medicine, Delamanid, Bedaquiline, Rifampicin, medicine.drug
Abstract: The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a compendium of 15,211 Mycobacterium tuberculosis global clinical isolates, all of which have undergone whole genome sequencing (WGS) and have had their minimum inhibitory concentrations to 13 antitubercular drugs measured in a single assay. It is the largest matched phenotypic and genotypic dataset for M. tuberculosis to date. Here, we provide a summary detailing the breadth of data collected, along with a description of how the isolates were collected and uniformly processed in CRyPTIC partner laboratories across 23 countries. The compendium contains 6,814 isolates resistant to at least one drug, including 2,129 samples that fully satisfy the clinical definitions of rifampicin resistant (RR), multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) or extensively drug resistant (XDR). Accurate prediction of resistance status (sensitive/resistant) to eight antitubercular drugs by using a genetic mutation catalogue is presented along with the presence of suspected resistance-conferring mutations for isolates resistant to the newly introduced drugs bedaquiline, clofazimine, delamanid and linezolid. Finally, a case study of rifampicin mono-resistance demonstrates how this compendium could be used to advance our genetic understanding of rare resistance phenotypes. The compendium is fully open-source and it is hoped that the dataset will facilitate and inspire future research for years to come.
Published: 2021
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49. Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

Author: Rungtiwa Nutalai, Daming Zhou, Aekkachai Tuekprakhon, Helen M. Ginn, Piyada Supasa, Chang Liu, Jiandong Huo, Alexander J. Mentzer, Helen M.E. Duyvesteyn, Aiste Dijokaite-Guraliuc, Donal Skelly, Thomas G. Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede Constantinides, Hermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, Neil G. Paterson, Mark A. Williams, David R. Hall, Juthathip Mongkolsapaya, Elizabeth E. Fry, Wanwisa Dejnirattisai, Jingshan Ren, David I. Stuart, Gavin R. Screaton, consortium, OPTIC, and consortium, ISARIC4C
Subjects: QR355, Epitopes, COVID-19 Vaccines, Neutralization Tests, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Antibodies, Monoclonal, COVID-19, Humans, Angiotensin-Converting Enzyme 2, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology
Abstract: Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.
Published: 2022
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50. Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales

Author: Kalisvar, Marimuthu, Indumathi, Venkatachalam, Vanessa, Koh, Stephan, Harbarth, Eli, Perencevich, Benjamin Pei Zhi, Cherng, Raymond Kok Choon, Fong, Surinder Kaur, Pada, Say Tat, Ooi, Nares, Smitasin, Koh Cheng, Thoon, Paul Anantharajah, Tambyah, Li Yang, Hsu, Tse Hsien, Koh, Partha Pratim, De, Thean Yen, Tan, Douglas, Chan, Rama Narayana, Deepak, Nancy Wen Sim, Tee, Andrea, Kwa, Yiying, Cai, Yik-Ying, Teo, Natascha May, Thevasagayam, Sai Rama Sridatta, Prakki, Weizhen, Xu, Wei Xin, Khong, David, Henderson, Nicole, Stoesser, David W, Eyre, Derrick, Crook, Michelle, Ang, Raymond Tzer Pin, Lin, Angela, Chow, Alex R, Cook, Jeanette, Teo, and Oon Tek, Ng
Subjects: Multidisciplinary, Bacterial Proteins, Whole Genome Sequencing, Enterobacteriaceae Infections, General Physics and Astronomy, Humans, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Gammaproteobacteria, beta-Lactamases, Retrospective Studies
Abstract: Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients’ admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.
Published: 2021

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