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1. Infectious disease surveillance needs for the United States: lessons from Covid-19

Author: Marc Lipsitch, Mary T. Bassett, John S. Brownstein, Paul Elliott, David Eyre, M. Kate Grabowski, James A. Hay, Michael A. Johansson, Stephen M. Kissler, Daniel B. Larremore, Jennifer E. Layden, Justin Lessler, Ruth Lynfield, Duncan MacCannell, Lawrence C. Madoff, C. Jessica E. Metcalf, Lauren A. Meyers, Sylvia K. Ofori, Celia Quinn, Ana I. Bento, Nicholas G. Reich, Steven Riley, Roni Rosenfeld, Matthew H. Samore, Rangarajan Sampath, Rachel B. Slayton, David L. Swerdlow, Shaun Truelove, Jay K. Varma, and Yonatan H. Grad
Subjects: pandemic, COVID-19, surveillance and forecast system, public health, infectious diseases, mathematical model, Public aspects of medicine, RA1-1270
Abstract: The COVID-19 pandemic has highlighted the need to upgrade systems for infectious disease surveillance and forecasting and modeling of the spread of infection, both of which inform evidence-based public health guidance and policies. Here, we discuss requirements for an effective surveillance system to support decision making during a pandemic, drawing on the lessons of COVID-19 in the U.S., while looking to jurisdictions in the U.S. and beyond to learn lessons about the value of specific data types. In this report, we define the range of decisions for which surveillance data are required, the data elements needed to inform these decisions and to calibrate inputs and outputs of transmission-dynamic models, and the types of data needed to inform decisions by state, territorial, local, and tribal health authorities. We define actions needed to ensure that such data will be available and consider the contribution of such efforts to improving health equity.
Published: 2024
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2. SARS-CoV-2, influenza A/B and respiratory syncytial virus positivity and association with influenza-like illness and self-reported symptoms, over the 2022/23 winter season in the UK: a longitudinal surveillance cohort

Author: Elisabeth Dietz, Emma Pritchard, Koen Pouwels, Muhammad Ehsaan, Joshua Blake, Charlotte Gaughan, Eric Haduli, Hugh Boothe, Karina-Doris Vihta, Tim Peto, Nicole Stoesser, Philippa Matthews, Nick Taylor, Ian Diamond, Ruth Studley, Emma Rourke, Paul Birrell, Daniela De Angelis, Tom Fowler, Conall Watson, David Eyre, Thomas House, and Ann Sarah Walker
Subjects: SARS-CoV-2, Respiratory syncytial virus, Influenza a/b, Influenza-like illness, Surveillance, Symptoms, Medicine
Abstract: Abstract Background Syndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses. Methods We estimated the positivity and incidence of SARS-CoV-2, influenza A/B, and RSV, and trends in self-reported symptoms including influenza-like illness (ILI), over the 2022/23 winter season in a broadly representative UK community cohort (COVID-19 Infection Survey), using negative-binomial generalised additive models. We estimated associations between test positivity and each of the symptoms and influenza vaccination, using adjusted logistic and multinomial models. Results Swabs taken at 32,937/1,352,979 (2.4%) assessments tested positive for SARS-CoV-2, 181/14,939 (1.2%) for RSV and 130/14,939 (0.9%) for influenza A/B, varying by age over time. Positivity and incidence peaks were earliest for RSV, then influenza A/B, then SARS-CoV-2, and were highest for RSV in the youngest and for SARS-CoV-2 in the oldest age groups. Many test positives did not report key symptoms: middle-aged participants were generally more symptomatic than older or younger participants, but still, only ~ 25% reported ILI-WHO and ~ 60% ILI-ECDC. Most symptomatic participants did not test positive for any of the three viruses. Influenza A/B-positivity was lower in participants reporting influenza vaccination in the current and previous seasons (odds ratio = 0.55 (95% CI 0.32, 0.95)) versus neither season. Conclusions Symptom profiles varied little by aetiology, making distinguishing SARS-CoV-2, influenza and RSV using symptoms challenging. Most symptoms were not explained by these viruses, indicating the importance of other pathogens in syndromic surveillance. Influenza vaccination was associated with lower rates of community influenza test positivity.
Published: 2024
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3. Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.

Author: Ronit Marom, Bo Zhang, Megan E Washington, I-Wen Song, Lindsay C Burrage, Vittoria C Rossi, Ava S Berrier, Anika Lindsey, Jacob Lesinski, Michael L Nonet, Jian Chen, Dustin Baldridge, Gary A Silverman, V Reid Sutton, Jill A Rosenfeld, Alyssa A Tran, M John Hicks, David R Murdock, Hongzheng Dai, MaryAnn Weis, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, Richard Caswell, Carrie Pottinger, Deirdre Cilliers, Karen Stals, Undiagnosed Diseases Network, David Eyre, Deborah Krakow, Tim Schedl, Stephen C Pak, and Brendan H Lee
Subjects: Genetics, QH426-470
Abstract: BackgroundKinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.MethodsTo understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, unc-116, at the corresponding position (Thr90Ile) by CRISPR/Cas9 editing and performed functional analysis. Next, we studied the cellular and molecular consequences of the recurrent p.Thr87Ile variant by microscopy, RNA and protein analysis in NIH3T3 cells, primary human fibroblasts and bone biopsy.ResultsC. elegans heterozygous for the unc-116 Thr90Ile variant displayed abnormal body length and motility phenotypes that were suppressed by additional copies of the wild type allele, consistent with a dominant negative mechanism. Time-lapse imaging of GFP-tagged mitochondria showed defective mitochondria transport in unc-116 Thr90Ile neurons providing strong evidence for disrupted kinesin motor function. Microscopy studies in human cells showed dilated endoplasmic reticulum, multiple intracellular vacuoles, and abnormal distribution of the Golgi complex, supporting an intracellular trafficking defect. RNA sequencing, proteomic analysis, and bone immunohistochemistry demonstrated down regulation of the mTOR signaling pathway that was partially rescued with leucine supplementation in patient cells.ConclusionWe report dominant negative variants in the KIF5B kinesin motor domain in individuals with osteogenesis imperfecta. This study expands the spectrum of kinesin-related disorders and identifies dysregulated signaling targets for KIF5B in skeletal development.
Published: 2023
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4. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O’Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan de Silva, David Eyre, Sheila Lumley, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, Chris P. Conlon, Katie Jeffery, Simon Travis, Philip Goulder, John Frater, Alex J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie
Subjects: Science
Abstract: The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.
Published: 2022
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5. A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study

Author: Emily Jefferson, Christian Cole, Shahzad Mumtaz, Samuel Cox, Thomas Charles Giles, Sam Adejumo, Esmond Urwin, Daniel Lea, Calum Macdonald, Joseph Best, Erum Masood, Gordon Milligan, Jenny Johnston, Scott Horban, Ipek Birced, Christopher Hall, Aaron S Jackson, Clare Collins, Sam Rising, Charlotte Dodsley, Jill Hampton, Andrew Hadfield, Roberto Santos, Simon Tarr, Vasiliki Panagi, Joseph Lavagna, Tracy Jackson, Antony Chuter, Jillian Beggs, Magdalena Martinez-Queipo, Helen Ward, Julie von Ziegenweidt, Frances Burns, Joanne Martin, Neil Sebire, Carole Morris, Declan Bradley, Rob Baxter, Anni Ahonen-Bishopp, Paul Smith, Amelia Shoemark, Ana M Valdes, Benjamin Ollivere, Charlotte Manisty, David Eyre, Stephanie Gallant, George Joy, Andrew McAuley, David Connell, Kate Northstone, Katie Jeffery, Emanuele Di Angelantonio, Amy McMahon, Mat Walker, Malcolm Gracie Semple, Jessica Mai Sims, Emma Lawrence, Bethan Davies, John Kenneth Baillie, Ming Tang, Gary Leeming, Linda Power, Thomas Breeze, Duncan Murray, Chris Orton, Iain Pierce, Ian Hall, Shamez Ladhani, Natalie Gillson, Matthew Whitaker, Laura Shallcross, David Seymour, Susheel Varma, Gerry Reilly, Andrew Morris, Susan Hopkins, Aziz Sheikh, and Philip Quinlan
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract: BackgroundCOVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom’s response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. ObjectiveWe aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). MethodsA federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners’ pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers’ secure environments, and to support federated cohort discovery queries and meta-analysis. ResultsA total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. ConclusionsCO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.
Published: 2022
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6. SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study

Author: Eleanor Barnes, David Eyre, Katie Jeffery, Jia Wei, Victoria Ward, William Gordon, Susie Dunachie, and Anne-Marie O’Donnell
Subjects: Medicine
Abstract: Objectives To examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.Design Cohort study.Setting Oxford University Hospitals in the United Kingdom.Participants Healthcare workers who had SARS-CoV-2 serological data available and received two SARS-CoV- 2 vaccinations.Primary outcome Peak SARS-CoV-2 anti-spike IgG responses after the second vaccination and associations with underlying health conditions and the estimated risk of severe COVID-19 using an occupational health risk assessment tool.Methods We used univariable and multivariable linear regression models to investigate associations between antibody levels and demographics (age, sex, ethnicity), healthcare role, body mass index, underlying health conditions, vaccination status, prior infection and the Association of Local Authority Medical Advisors COVID-age risk score.Results 1635 HCWs had anti-spike IgG measurements 14–84 days after second vaccination and data on any underlying health conditions. Only five HCWs (0.3%), all on immunosuppressive treatment, (including four organ transplant recipients), did not seroconvert after second vaccination. Antibody levels were independently lower with older age, diabetes, immunosuppression, respiratory disorders other than asthma and markedly so in organ transplant recipients. Levels were independently lower in ChAdOx1 versus BNT162b2 recipients and higher following previous infection. HCWs with ‘very high’ COVID-age risk scores had lower median antibody levels than those with ‘low’, ‘medium’ or ‘high’ risk scores; 4379 AU/mL, compared with 12 337 AU/mL, 9430 AU/mL and 10 524 AU/mL, respectively.Conclusions Two vaccine doses are effective in generating antibody responses among HCWs, including those with a high occupational risk. However, HCWs with underlying health conditions, especially diabetes, immunosuppression and organ transplant, had lower antibody levels, and vaccine response monitoring may be needed.
Published: 2022
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7. T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author: Ane Ogbe, Barbara Kronsteiner, Donal T. Skelly, Matthew Pace, Anthony Brown, Emily Adland, Kareena Adair, Hossain Delowar Akhter, Mohammad Ali, Serat-E Ali, Adrienn Angyal, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Helen Brown, Senthil Chinnakannan, Christopher Conlon, Catherine de Lara, Thushan de Silva, Christina Dold, Tao Dong, Timothy Donnison, David Eyre, Amy Flaxman, Helen Fletcher, Joshua Gardner, James T. Grist, Carl-Philipp Hackstein, Kanoot Jaruthamsophon, Katie Jeffery, Teresa Lambe, Lian Lee, Wenqin Li, Nicholas Lim, Philippa C. Matthews, Alexander J. Mentzer, Shona C. Moore, Dean J. Naisbitt, Monday Ogese, Graham Ogg, Peter Openshaw, Munir Pirmohamed, Andrew J. Pollard, Narayan Ramamurthy, Patpong Rongkard, Sarah Rowland-Jones, Oliver Sampson, Gavin Screaton, Alessandro Sette, Lizzie Stafford, Craig Thompson, Paul J. Thomson, Ryan Thwaites, Vinicius Vieira, Daniela Weiskopf, Panagiota Zacharopoulou, Oxford Immunology Network Covid-19 Response T Cell Consortium, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, Lance Turtle, Paul Klenerman, Philip Goulder, John Frater, Eleanor Barnes, and Susanna Dunachie
Subjects: Science
Abstract: Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.
Published: 2021
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8. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author: Adrienn Angyal, PhD, Stephanie Longet, PhD, Shona C Moore, PhD, Rebecca P Payne, DPhil, Adam Harding, MSc, Tom Tipton, PhD, Patpong Rongkard, MSc, Mohammad Ali, MD, Luisa M Hering, MSc, Naomi Meardon, MBChB, James Austin, PhD, Rebecca Brown, PhD, Donal Skelly, PhD, Natalie Gillson, BSc, Sue L Dobson, MSc, Andrew Cross, PhD, Gurjinder Sandhar, MSc, Jonathan A Kilby, MSc, Jessica K Tyerman, BSc, Alexander R Nicols, MSc, Jarmila S Spegarova, PhD, Hema Mehta, DPhil, Hailey Hornsby, MSc, Rachel Whitham, MSc, Christopher P Conlon, ProfPhD, Katie Jeffery, PhD, Philip Goulder, ProfDPhil, John Frater, ProfPhD, Christina Dold, PhD, Matthew Pace, PhD, Ane Ogbe, PhD, Helen Brown, BSc, M Azim Ansari, DPhil, Emily Adland, PhD, Anthony Brown, BSc, Meera Chand, FRCPath, Adrian Shields, PhD, Philippa C Matthews, PhD, Susan Hopkins, PhD, Victoria Hall, PhD, William James, ProfDPhil, Sarah L Rowland-Jones, ProfDM, Paul Klenerman, ProfPhD, Susanna Dunachie, ProfPhD, Alex Richter, ProfPhD, Christopher J A Duncan, DPhil, Eleanor Barnes, ProfPhD, Miles Carroll, ProfPhD, Lance Turtle, PhD, Thushan I de Silva, PhD, Adam Harding, Adam Watson, Adrian Shields, Adrienn Angyal, Ahmed Alhussni, Alex Richter, Alexander Nicols, Alexandra Deeks, Alice Webb-Bridges, Andrew Cross, Ane Ogbe, Anni Jämsén, Anthony Brown, Anu Chawla, Christina Dold, Christopher Duncan, Christopher Conlon, Donal Skelly, Denise O'Donnell, Eleanor Barnes, Emily Adland, Esme Weeks, Gurjinder Sandhar, Hailey Hornsby, Helen Brown, Hema Mehta, Hibatullah Abuelgasim, Huiyuan Xiao, James Austin, Jarmila Spegarova, Jennifer Holmes, Jenny Haworth, Jessica Tyerman, John Frater, Jonathan Kilby, Joseph Cutteridge, Katie Jeffery, Katy Lillie, Lance Turtle, Leigh Romaniuk, Lucy Denly, Luisa Hering, M. Azim Ansari, Matthew Pace, Meera Chand, Miles Carroll, Mohammad Ali, Mwila Kasanyinga, Naomi Meardon, Natalie Gillson, Patpong Rongkard, Paul Klenerman, Philip Goulder, Philippa Matthews, Rachel Whitham, Rebecca Brown, Rebecca Payne, Robert Wilson, Sarah Rowland-Jones, Sarah Thomas, Shona Moore, Siobhan Gardiner, Stephanie Longet, Stephanie Tucker, Sue Dobson, Susan Hopkins, Susanna Dunachie, Syed Adlou, Thushan de Silva, Tom Tipton, Victoria Hall, William James, Allan Lawrie, Nikki Smith, Helena Turton, Amira Zawia, Martin Bayley, Alex Fairman, Kate Harrington, Rosemary Kirk, Louise Marsh, Lisa Watson, Steven Wood, Benjamin Diffey, Chris Jones, Lauren Lett, Gareth Platt, Krishanthi Subramaniam, Daniel Wootton, Brendan Payne, Sophie Hambleton, Sinead Kelly, Judith Marston, Sonia Poolan, Dianne Turner, Muzlifah Haniffa, Emily Stephenson, Sandra Adele, Hossain Delowar Akhter, Senthil Chinnakannan, Catherine de Lara, Timothy Donnison, Carl-Philipp Hackstein, Lian Lee, Nicholas Lim, Tom Malone, Eloise Phillips, Narayan Ramamurthy, Nichola Robinson, Oliver Sampson, David Eyre, Beatrice Simmons, Lizzie Stafford, Alexander Mentzer, Ali Amini, Carolina Arancibia-Cárcamo, Nicholas Provine, Simon Travis, Stavros Dimitriadis, Sile Johnson, Sarah Foulkes, Jameel Khawam, Edgar Wellington, Javier Gilbert-Jaramillo, Michael Knight, Maeva Dupont, Emily Horner, James Thaventhiran, and Jeremy Chalk
Subjects: Medicine (General), R5-920, Microbiology, QR1-502
Abstract: Summary: Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. Methods: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3–4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. Findings: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232–285). At 28 days (IQR 27–33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150–461] vs 55 [IQR 24–132] spot-forming units [SFUs] per 106 PBMCs; p
Published: 2022
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9. 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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10. 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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11. The global challenge of Candida auris in the intensive care unit

Author: Andrea Cortegiani, Giovanni Misseri, Antonino Giarratano, Matteo Bassetti, and David Eyre
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2019
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12. Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure.

Author: Marco Maccarana, René B Svensson, Anki Knutsson, Antonis Giannopoulos, Mea Pelkonen, MaryAnn Weis, David Eyre, Matthew Warman, and Sebastian Kalamajski
Subjects: Medicine, Science
Abstract: The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn-/- mice (not statistically significant). Several matrix genes were upregulated, including collagens (Col1a1, Col1a2, Col3a1), matrix metalloproteinases (Mmp2, Mmp3) and lysyl oxidases (Lox, Loxl2), while lysyl hydroxylase (Plod2) was downregulated. Intriguingly no differences were observed in collagen protein content or in collagen cross-linking-related lysine oxidation or hydroxylation. The glycosaminoglycan content and structure in Aspn-/- skin was profoundly altered: chondroitin/dermatan sulfate was more than doubled and had an altered composition, while heparan sulfate was halved and had a decreased sulfation. Also, decorin and biglycan were doubled in Aspn-/- skin. Overall, asporin deficiency changes skin glycosaminoglycan composition, and decorin and biglycan content, which may explain the changes in skin mechanical properties.
Published: 2017
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13. Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.

Author: Erica P Homan, Caressa Lietman, Ingo Grafe, Jennifer Lennington, Roy Morello, Dobrawa Napierala, Ming-Ming Jiang, Elda M Munivez, Brian Dawson, Terry K Bertin, Yuqing Chen, Rhonald Lua, Olivier Lichtarge, John Hicks, Mary Ann Weis, David Eyre, and Brendan H L Lee
Subjects: Genetics, QH426-470
Abstract: Mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1) were the first identified causes of recessive Osteogenesis Imperfecta (OI). These proteins, together with cyclophilin B (encoded by PPIB), form a complex that 3-hydroxylates a single proline residue on the α1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A) ). This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I) and α1(II) collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity versus complete ablation of the prolyl 3-hydroxylation complex.
Published: 2014
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14. New Zealand’s New Road Safety Strategy

Author: David Eyre
Subjects: Transportation and communications, HE1-9990
Abstract: In March this year, Transport Minister Steven Joyce launched a new strategy for reducing the impact of road crashes over the next decade. Safer journeys: New Zealand’s road safety strategy 2010-2020 proposes significant changes to help improve New Zealand’s road safety. These include raising the driving age from 15 to 16, introducing a zero drink drive limit for under 20s, changing the give way rules for turning traffic and reconsidering the adult drink drive limit. The initiatives in Safer journeys are underpinned by a Safe System approach to road safety, which focuses on actions across the entire road system: roads and roadsides, speeds, vehicles and road use. The strategy also aims to address a number of road safety priorities, such as the safety of young drivers and the impact of drugs and alcohol on road safety. The strategy was developed by the National Road Safety Committee (NRSC). The NRSC is led by the Ministry of Transport and includes the New Zealand Police, the NZ Transport Agency, the Accident Compensation Corporation and Local Government New Zealand. From the start, public consultation has been a key part of the strategy. We have aimed to strike a balance between feedback received, resources available to implement change, and the evidence and research. This recognises the importance of both research and public support for road safety actions.
Published: 2010

15. Infectious disease surveillance needs for the United States: lessons from COVID-19.

Author: Marc Lipsitch, Mary T. Bassett, John S. Brownstein, Paul Elliott, David Eyre, M. Kate Grabowski, James A. Hay, Michael A. Johansson, Stephen M. Kissler, Daniel B. Larremore, Jennifer Layden, Justin Lessler, Ruth Lynfield, Duncan MacCannell, Lawrence C. Madoff, C. Jessica E. Metcalf, Lauren Ancel Meyers, Sylvia K. Ofori, Celia Quinn, Ana I. Ramos Bento, Nick Reich, Steven Riley, Roni Rosenfeld, Matthew H. Samore, Rangarajan Sampath, Rachel B. Slayton, David L. Swerdlow, Shaun Truelove, Jay K. Varma, and Yonatan H. Grad
Published: 2023
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16. Mode Connections For Clinical Incremental Learning: Lessons From The COVID-19 Pandemic

Author: Anshul Thakur, Chenyang Wang, Taha Ceritli, David Clifton, and David Eyre
Abstract: Dynamic distribution shifts caused by evolving diseases and demographic changes require domain-incremental adaptation of clinical deep learning models. However, this process of adaptation is often accompanied bycatastrophic forgetting, and even the most sophisticated methods are not good enough for clinical applications. This paper studies incremental learning from the perspective ofmode connections, that is, the low-loss paths connecting the minimisers of neural architectures (modes or trained weights) in the parameter space. The paper argues for learning the low-loss paths originating from an existing mode and exploring the learned paths to find an acceptable mode for the new domain. The learned paths, and hence the new domain mode, are afunctionof the existing mode. As a result, unlike traditional incremental learning, the proposed approach is able to exploit information from a deployed model without changing its weights. Pre-COVID and COVID-19 data collected in Oxford University hospitals are used as a case study to demonstrate the need for domain-incremental learning and the advantages of the proposed approach.
Published: 2023

17. Performance of antigen lateral flow devices in the United Kingdom during the Alpha, Delta, and Omicron waves of the SARS-CoV-2 pandemic

Author: David Eyre, Matthias Futschik, Sarah Tunkel, Jia Wei, Joanna Cole-Hamilton, Rida Saquib, Nick Germanacos, Andrew R Dodgson, Paul E Klapper, Malur Sudhanva, Chris Kenny, Peter Marks, Edward Blandford, Susan Hopkins, Tim Peto, and Tom Fowler
Abstract: BackgroundAntigen lateral flow devices (LFDs) have been widely used to control SARS-CoV-2. Changes in LFD sensitivity and detection of infectious individuals during the pandemic with successive variants, vaccination, and changes in LFD use are incompletely understood.MethodsPaired LFD and PCR tests were collected from asymptomatic and symptomatic participants, across multiple settings in the UK between 04-November-2020 and 21-March-2022. Multivariable logistic regression was used to analyse LFD sensitivity and specificity, adjusting for viral load, LFD manufacturer, setting, age, sex, assistance, symptoms, vaccination, and variant. National contact tracing data were used to estimate the proportion of transmitting index cases (with ≥1 PCR/LFD-positive contact) potentially detectable by LFDs over time, accounting for viral load, variant, and symptom status.Findings4131/75,382 (5.5%) participants were PCR-positive. Sensitivity vs. PCR was 63.2% (95%CI 61.7-64.6%) and specificity 99.71% (99.66-99.74%). Increased viral load was independently associated with being LFD-positive. There was no evidence LFD sensitivity differed between Delta vs. Alpha/pre-Alpha infections, but Omicron infections were more likely to be LFD positive. Sensitivity was higher in symptomatic participants, 68.7% (66.9-70.4%) than in asymptomatic participants, 52.8% (50.1-55.4%). 79.4% (68.6-81.3%) of index cases resulting in probable onward transmission with were estimated to have been detectable using LFDs, this proportion was relatively stable over time/variants, but lower in asymptomatic vs. symptomatic cases.InterpretationLFDs remained able to detect most SARS-CoV-2 infections throughout vaccine roll-out and different variants. LFDs can potentially detect most infections that transmit to others and reduce risks. However, performance is lower in asymptomatic compared to symptomatic individuals.FundingUK Government.Research in contextEvidence before this studyLateral flow devices (LFDs; i.e. rapid antigen detection devices) have been widely used for SARS-CoV-2 testing. However, due to their imperfect sensitivity when compared to PCR and a lack of a widely available gold standard proxy for infectiousness, the performance and use of LFDs has been a source of debate. We conducted a literature review in PubMed and bioRxiv/medRxiv for all studies examining the performance of lateral flow devices between 01 January 2020 and 31 October 2022. We used the search terms ‘SARS-CoV-2’/’COVID-19’ and ‘antigen’/’lateral flow test’/’lateral flow device’. Multiple studies have examined the sensitivity and specificity of LFDs, including several systematic reviews. However, the majority of the studies are based on pre-Alpha infections. Large studies examining the test accuracy for different variants, including Delta and Omicron, and following vaccination are limited.Added value of this studyIn this large national LFD evaluation programme, we compared the performance of three different LFDs relative to PCR in various settings. Compared to PCR testing, sensitivity was 63.2% (95%CI 61.7-64.6%) overall, and 71.6% (95%CI 69.8-73.4%) in unselected communitybased testing. Specificity was 99.71% (99.66-99.74%). LFDs were more likely to be positive as viral loads increased. LFD sensitivity was similar during Alpha/pre-Alpha and Delta periods but increased during the Omicron period. There was no association between sensitivity and vaccination status. Sensitivity was higher in symptomatic participants, 68.7% (66.9-70.4%) than in asymptomatic participants, 52.8% (50.1-55.4%). Using national contact tracing data, we estimated that 79.4% (68.6-81.3%) of index cases resulting in probable onward transmission (i.e. with ≥1 PCR/LFD-positive contact) were detectable using LFDs. Symptomatic index cases were more likely to be detected than asymptomatic index cases due to higher viral loads and better LFD performance at a given viral load. The proportion of index cases detected remained relatively stable over time and with successive variants, with a slight increase in the proportion of asymptomatic index cases detected during Omicron.Implications of all the available evidenceOur data show that LFDs detect most SARS-CoV-2 infections, with findings broadly similar to those summarised in previous meta-analyses. We show that LFD performance has been relatively consistent throughout different variant-dominant phases of the pandemic and following the roll-out of vaccination. LFDs can detect most infections that transmit to others and can therefore be used as part of a risk reduction strategy. However, performance is lower in asymptomatic compared to symptomatic individuals and this needs to be considered when designing testing programmes.
Published: 2022

18. Benchmarking taxonomic classifiers with Illumina and Nanopore sequence data for clinical metagenomic diagnostic applications

Author: David Eyre and Kumeren Govender
Subjects: Nanopores, Benchmarking, Nucleotides, Humans, High-Throughput Nucleotide Sequencing, General Medicine, Metagenomics
Abstract: Culture-independent metagenomic detection of microbial species has the potential to provide rapid and precise real-time diagnostic results. However, it is potentially limited by sequencing and classification errors. We use simulated and real-world data to benchmark rates of species misclassification using 100 reference genomes for each of ten common bloodstream pathogens and six frequent blood culture contaminants (n=1600). Simulating both with and without sequencing error for both the Illumina and Oxford Nanopore platforms, we evaluated commonly used classification tools including Kraken2, Bracken, and Centrifuge, utilising mini (8GB) and standard (30-50GB) databases. Bracken with the standard database performed best, the median percentage of reads across both sequencing platforms identified correctly to the species level was 98.46% (IQR 93.0:99.3) [range 57.1:100]. For Kraken2 with a mini database, a commonly used combination, median species-level identification was 79.3% (IQR 39.1:88.8) [range 11.2:100]. Classification performance varied by species, with E. coli being more challenging to classify correctly (59.4% to 96.4% reads with correct species, varying by tool used). By filtering out shorter Nanopore reads (ImportanceMetagenomics may transform clinical microbiology by enabling more rapid species detection in a potentially unbiased manner and reducing reliance on culture-based approaches. However, it is still limited by ongoing challenges such as sequencing and classification software errors. In this study, we use simulated and real-world data to define the intrinsic rates of species misclassification that occur using Illumina and Oxford Nanopore sequencing platforms with commonly used taxonomic classification tools and databases. We quantify the extent of “bioinformatic contamination” arising from the classification process. This enables us to identify the best performing tools that maximize classification accuracy, and to suggest how taxonomic misclassification can be formally accounted for in clinical diagnostic workflows. Specifically, we specify thresholds for identifying or excluding polymicrobial infections in metagenomic samples, based on rates of misclassification of similar species, which might have clinical implications when treating infection.
Published: 2022

19. RapiD_AI: A framework for Rapidly Deployable AI for novel disease & pandemic preparedness

Author: Alexey Youssef, Tingting Zhu, Anshul Thakur, Peter Watkinson, Peter Horby, David Eyre, and David Clifton
Abstract: COVID-19 is unlikely to be the last pandemic that we face. According to an analysis of a global dataset of historical pandemics from 1600 to the present, the risk of a COVID-like pandemic has been estimated as 2.63% annually or a 38% lifetime probability. This rate may double over the coming decades. While we may be unable to prevent future pandemics, we can reduce their impact by investing in preparedness. In this study, we propose RapiD AI : a framework to guide the use of pretrained neural network models as a pandemic preparedness tool to enable healthcare system resilience and effective use of ML during future pandemics. The RapiD AI framework allows us to build highperforming ML models using data collected in the first weeks of the pandemic and provides an approach to adapt the models to the local populations and healthcare needs. The motivation is to enable healthcare systems to overcome data limitations that prevent the development of effective ML in the context of novel diseases. We digitally recreated the first 20 weeks of the COVID-19 pandemic and experimentally demonstrated the RapiD AI framework using domain adaptation and inductive transfer. We (i) pretrain two neural network models (Deep Neural Network and TabNet) on a large Electronic Health Records dataset representative of a general in-patient population in Oxford, UK, (ii) fine-tune using data from the first weeks of the pandemic, and (iii) simulate local deployment by testing the performance of the models on a held-out test dataset of COVID-19 patients. Our approach has demonstrated an average relative/absolute gain of 4.92/4.21% AUC compared to an XGBoost benchmark model trained on COVID-19 data only. Moreover, we show our ability to identify the most useful historical pretraining samples through clustering and to expand the task of deployed models through inductive transfer to meet the emerging needs of a healthcare system without access to large historical pretraining datasets.
Published: 2022

20. Detecting changes in population trends in infection surveillance using community SARS-CoV-2 prevalence as an exemplar

Author: Philippa Matthews, David Eyre, Emma Pritchard, Brent Brown, and Nicole Stoesser
Abstract: BackgroundMonitoring infection trends is vital to informing public health strategy. Detecting and quantifying changes in growth rates can inform policymakers’ rationale for implementing or continuing interventions aimed at reducing impact. Substantial changes in SARS-CoV-2 prevalence with emergence of variants provides opportunity to investigate different methods to do this.MethodsWe included PCR results from all participants in the UK’s COVID-19 Infection Survey between 1 August 2020-30 June 2022. Change-points for growth rates were identified using iterative sequential regression (ISR) and second derivatives of generalised additive models (GAMs).Consistency between methods and timeliness of detection were compared.FindingsOf 8,799,079 visits, 147,278 (1·7%) were PCR-positive. Over the time period, change-points associated with emergence of major variants were estimated to occur a median 4 days earlier (IQR 0-8) in GAMs versus ISR, with only 2/48 change-points identified by only one method. Estimating recent change-points using successive data periods, four change-points (4/96) identified by GAMs were not found when adding later data or by ISR; 77% (74/96) of change-points identified by successive GAMs were identified by ISR. Change-points were detected 3-5 weeks after they occurred in both methods but could be detected earlier within specific subgroups.InterpretationChange-points in growth rates of SARS-CoV-2 can be detected in near real-time using ISR and second derivatives of GAMs. To increase certainty about changes in epidemic trajectories both methods could be run in parallel. Running either method in near real-time on different infection surveillance data streams could provide timely warnings of changing underlying epidemiology.FundingUK Health Security Agency, 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: 2022

21. 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

22. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Adriana, Tomic, Donal T, Skelly, Ane, Ogbe, Daniel, O'Connor, Matthew, Pace, Emily, Adland, Frances, Alexander, Mohammad, Ali, Kirk, Allott, M, Azim Ansari, Sandra, Belij-Rammerstorfer, Sagida, Bibi, Luke, Blackwell, Anthony, Brown, Helen, Brown, Breeze, Cavell, Elizabeth A, Clutterbuck, Thushan, de Silva, David, Eyre, Sheila, Lumley, Amy, Flaxman, James, Grist, Carl-Philipp, Hackstein, Rachel, Halkerston, Adam C, Harding, Jennifer, Hill, Tim, James, Cecilia, Jay, Síle A, Johnson, Barbara, Kronsteiner, Yolanda, Lie, Aline, Linder, Stephanie, Longet, Spyridoula, Marinou, Philippa C, Matthews, Jack, Mellors, Christos, Petropoulos, Patpong, Rongkard, Cynthia, Sedik, Laura, Silva-Reyes, Holly, Smith, Lisa, Stockdale, Stephen, Taylor, Stephen, Thomas, Timothy, Tipoe, Lance, Turtle, Vinicius Adriano, Vieira, Terri, Wrin, Andrew J, Pollard, Teresa, Lambe, Chris P, Conlon, Katie, Jeffery, Simon, Travis, Philip, Goulder, John, Frater, Alex J, Mentzer, Lizzie, Stafford, Miles W, Carroll, William S, James, Paul, Klenerman, Eleanor, Barnes, Christina, Dold, Nick P, Talbot, Group, OPTIC Clinical, and Group, PITCH Study
Subjects: Multidisciplinary, SARS-CoV-2, Spike Glycoprotein, Coronavirus, COVID-19, Humans, General Physics and Astronomy, Longitudinal Studies, General Chemistry, Antibodies, Viral, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology
Abstract: The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
Published: 2022

23. 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 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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, 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Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael Eze Chukwu, Izu Chukwulobelu, Chi Yee Chung, 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, Zoe Clark, Andrea Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Kate Clay, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Francesca Clemons, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Michelle 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Patrycja Czylok, Silvia D'Arcangelo, Joana da Rocha, Andrew Dagens, Helen Daggett, Jacqui Daglish, Sandeep Dahiya, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Jolyon Dales, Helen Dalgleish, Helen Dallow, Dermot Dalton, Zoe Daly, Eleanor Damm, Akila Danga, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Sandra Danso-Bamfo, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Kate Darlington, Sarah Darnell, Tom Darton, Guledew Darylile, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Vaishali Dave, Emily Davenport, Mark Davey, Miriam Davey, Molly Davey, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Amanda Davies, Amy Davies, Angela Davies, Carolyn Davies, Catrin Davies, Drew Davies, Elaine Davies, Ffyon Davies, Helen Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa 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, 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 Denmade, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Usha Devkota, Prakash Dey, Vishal Dey, Rogin Deylami, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Meghnath Dhimal, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Debbie Dickerson, Pamela Dicks, Stuart Dickson, J Digby, Sean Dillane, Sarah Diment, Paul Dimitri, Thai Ha Dinh, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Caroline Dixon, Giles Dixon, Brice Djeugam, Petr Dlouhy, Andrea D'Mello, Paul Dmitri, 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 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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, Natalie Duric, Alison Durie, Emily Durie, Hannah Durrington, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Laura Eagles, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Amy Easthope, Fraser Easton, Ruth Eatough, Oluwadamilola Ebigbola, Daniel Ebner, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Jenny Eedle, Dawn Egginton, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Diana Eleanor, Ibrahim Eletu, Eman 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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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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 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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 Grigoriadou, Steph Grigsby, 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, Anju Gurung, Bhawana Gurung, Shraddha Gurung, Hazel Guth, Pradip Gyanwali, Ruth Habibi, Berkin Hack, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Nikolaos Hadjisavvas, 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, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Raph Hamers, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, Jude Hampson, Lucy Hampson, Ozan Hanci, Sadiyah Hand, Jasmine Handford, Soran Handrean, Sarah Haney, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Anita Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Mazhar Ul Haq, Ala Haqiqi, Monjurul Haque, Lesley Harden, Zoe Harding, Simon Hardman, Joanna Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward 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Val Irvine, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Samsul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Monica Ivan, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Ben Jackson, Beth Jackson, Ella Jackson, Helen Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Patricia Jacob, Reni Jacob, Nicola Jacques, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, 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, Deepa Japp, Victor Jardim, Catherine Jardine, Emma 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Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Claire Johnston, Janet 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, Jac Jones, James Jones, Jonathon Jones, Julie Jones, Kate E Jones, Laura Jones, Laura M 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, Sanal Jose, Anna Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi 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, Nikhil 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Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Teresa Maria Pfyl, Victor Mariano, Ashleigh Maric, Grace Markham, Maria Marks, P Marks, Elisabeth Marouzet, Arran Marriott, Cheryl Marriott, Nemonie Marriott, Brian Marsden, Christopher Marsden, Karen Marsden, Paul Marsden, Sarah Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, Jenna Marshall, Nicola Marshall, Riley Marshall, Jennifer Marshall, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Kate Martin, Laila Martin, Michael Martin, Noelia Martin, Tim Martin, Winston Martin, Sarah Martin, Tim Martindale, Marcus Martineau, Lauren Martinez, Jose C Martinez Garrido, Juan Martin-Lazaro, Lucas Martins Ferreira, Vijay K Maruthamuthu, Gemma Maryan, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Al Mashta, Izhaq Masih, Sanna Masih, Nick Maskell, Perry Maskell, Matthew Masoli, Rebecca Mason, Richard Mason, Ruth Mason, Claire Mason, Mohammad Masood, Mohammad T Masood, Syed S M E Masood, Aaqib Masud, Lear Matapure, Cristina Matei, Ropafadzo Matewe, Manraj Matharu, Stephy Mathen, Alex Mather, Nicole Mather, Jonathan Mathers, Joanna Matheson, Amal Mathew, Anna Mathew, Moncy Mathew, Verghese Mathew, Jesha Mathews, Kate Mathias, Alexander Mathioudakis, Darwin Matila, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Jaysankar Mattappillil, Alison J Matthews, Heather Matthews, Helen Matthews, Fiona Maxton, Adam Maxwell, Veronica Maxwell, James May, Joanne May, Philippa May, Irving Mayanagao, Matthew Maycock, Graham Mayers, Victoria Maynard, Shelley Mayor, Ibreaheim Mazen, Andrea Mazzella, Nyambura Mburu, Eleanor McAleese, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, Claire McBrearty, Erin McBride, Michael 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Michael, Shery Michael, Natalia Michalak, Loredana Michalca-Mason, Janet Middle, Hayley Middleton, Jennifer T Middleton, Maeve Middleton, Sophie Middleton, Shelley Mieres, Loredana Mihalca-Mason, Theresia Mikolasch, Sarah Milgate, Colin Millar, Jonathan Millar, James Millard, David Miller, Johnathan Miller, Lucy Miller, Rachel Miller, Naomi Miller-Biot, Alex Miller-Fik, Louise Millett, Hazel Milligan, Iain Milligan, Caitlin Milliken, Katherine Millington, Samuel Millington, Helen Mills, Janet Mills, Helen Millward, Sebastian Millward, Rebecca Miln, Alice Milne, Charlotte Milne, Louise Milne, Joanne Milner, Zayar Min, Samuel Mindel, Chrissie Minnis, Paul Minnis, Jane Minton, Frederico Miranda, Taimur Mirza, Anjum Misbahuddin, Aseem Mishra, Biswa Mishra, Eleanor Mishra, Ritu Mishra, Sannidhya Misra, Deena Mistry, Heena Mistry, Dushyant Mital, Sarah Mitchard, Ben Mitchell, Piers Mitchell, Philip Mitchelmore, Andrew Mitra, Atideb Mitra, Sandip Mitra, Emma Moakes, Emma Moatt, Gita Modgil, 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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McDonald Mupudzi, Arshid Murad, Oluwatosin H Muraina, Koteshwara Muralidhara, Mhairi Murdoch, Jennifer Murira, Alison Murphy, Carl Murphy, Gail Murphy, Peter Murphy, Sheenagh Murphy, Simon Murphy, Clare Murray, David Murray, Eleanor Murray, Katie Murray, Kenneth Murray, Lisa Murray, Lorna Murray, Tracey Murray, Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Omaisa Mushtaq, Ahmed M M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Zhain Mustufvi, Callum Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, Khin Swe Myint, Yadee Myint, Libor Myslivecek, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Thapas Nagarajan, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, 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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Declan Ryan-Wakeling, M Saad, Javeson Sabale, Suganya Sabaretnam, Noman Sadiq, Emma Sadler, Ashiq Saffy, Beth Sage, Harkiran Sagoo, Sobia Sagrir, Rajnish Saha, Sian Saha, Nikhil Sahdev, Sarvjit Sahedra, Jagdeep Sahota, Nooria Said, Sreekanth Sakthi, Hikari Sakuri, Murthy Saladi, Abdul Salam, Armorel Salberg, Erika Salciute, Gina Saleeb, Mumtaz Saleh, Hizni Salih, Laylan Salih, Sarah Salisbury, SiteEneye Saliu, Rustam Salman, Jenny Salmon, Dario Salutous, Mfon Sam, Sally Sam, Tinashe Samakomva, Razan Saman, Sakeena Samar, Renaldo Samlal, Emily Sammons, David Sammut, Mark Sammut, Sunitha Sampath, Claire Sampson, Julia Sampson, Aashna Samson, Anda Samson, Johnson Samuel, Merna Samuel, Reena Samuel, Thomas D L Samuel, Younan Samuel, Theo Samuels, Joanna Samways, Manjula Samyraju, Ilves Sana, Veronica Sanchez, Amada Sanchez Gonzalez, Alina Sanda-Gomez, Peter Sandercock, Amy Sanderson, Tom Sanderson, Prabowo Sandhi, Kuljinder Sandhu, Loveleen Sandhu, Sam Sandow, Victoria Sandrey, Sarah Sands, Mirriam Sangombe, Mathew Sanju, Lakshmi Sankaran, Filipa Santos, Rojy Santosh, Jayanta Sanyal, Aureo F Sanz-Cepero, Dan Saragih, Dinesh Saralaya, Arun Saraswatula, Joshua Sarella, Avishay Sarfatti, Rebecca Sargent, Beatrix Sari, Diah Sari, Khatija Sarkar, Rahuldeb Sarkar, Sruthi Sarma, Zainab Sarwar, Thea Sass, Sonia Sathe, Sobitha Sathianandan, Abilash Sathyanarayanan, Lavanya S J P Sathyanarayanan, Thozhukat Sathyapalan, Prakash Satodia, Vera Saulite, Andrew Saunders, Rachel Saunders, Samantha Saunders, Anne Saunderson, Heather Savill, Karishma Savlani, Gauri Saxena, Matthew Saxton, Amrinder Sayan, Diane Scaletta, Deborah Scanlon, Jeremy Scanlon, Lyndsay Scarratt, Sean Scattergood, Alvin Schadenberg, Jenna Schafers, Wendy Schneblen, Rebecca Schofield, Samuel Schofield, David Scholes, Karen Scholes, Alex Schoolmeesters, Natasha Schumacher, Nicola Schunke, Martin Schuster Bruce, Karin Schwarz, Antonia Scobie, Tim Scorrer, A. 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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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Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Thin Wan, Junita Wanda, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Joanna Ward, Luke Ward, Nicola Ward, Rachael Ward, Thomas Ward, Tom Ward, Scott A Warden, Steve Wardle, Hassan Wardy, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Adilia Warris, Gill Warwick, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Abigail Watson, Adam J R Watson, Ekaterina Watson, Eleanor Watson, J G R Watson, Paul Watson, Rebecca Watson, Robert Watson, Malcolm Watters, 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White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Sophie Whiteley, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, 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Francesca Wright, Imogen Wright, Lianne Wright, Rachel Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Zhongyang Xia, Huiyuan Xiao, Masseh Yakubi, May Yan, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Peter Yew, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise 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, Shakir Zaman, Julie Zamikula, 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

24. Comparison of two T cell assays to evaluate T cell responses to SARS-CoV-2 following vaccination in naïve and convalescent healthcare workers

Author: David Eyre, Ashley Otter, Susanna Dunachie, Christopher Duncan, Lizzie Stafford, Lance Turtle, Thushan De Silva, Alexandra Deeks, Eloise Phillips, Donal Skelly, Susan Dobson, Eleanor Barnes, and Sandra Adele
Abstract: BackgroundT cell responses to SARS-CoV-2 following infection and vaccination are less characterised than antibody responses, due to a more complex experimental pathway.MethodsWe measured T cell responses in 108 healthcare workers (HCWs) in an observational cohort study, using the commercialised Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay (OI T-SPOT) and the PITCH ELISpot protocol established for academic research settings.ResultsBoth assays detected T cell responses to SARS-CoV-2 spike, membrane and nucleocapsid proteins. Responses were significantly lower when reported by OI T-SPOT than by PITCH ELISpot. Four weeks after two doses of either Pfizer/BioNTech BNT162b or ChAdOx1 nCoV-19 AZD1222 vaccine, the responder rate was 63% for OI T-SPOT Panels1+2 (peptides representing SARS-CoV-2 spike protein excluding regions present in seasonal coronaviruses), 69% for OI T-SPOT Panel 14 (peptides representing the entire SARS-CoV-2 spike), and 94% for the PITCH ELISpot assay. The two OI T-SPOT panels correlated strongly with each other showing that either readout quantifies spike-specific T cell responses, although the correlation between the OI T-SPOT panels and the PITCH ELISpot was moderate.ConclusionThe standardisation, relative scalability and longer interval between blood acquisition and processing are advantages of the commercial OI T-SPOT assay. However, the OI T-SPOT assay measures T cell responses at a significantly lower magnitude compared to the PITCH ELISpot assay, detecting T cell responses in a lower proportion of vaccinees. This has implications for the reporting of low-level T cell responses that may be observed in patient populations and for the assessment of T cell durability after vaccination.
Published: 2022

25. Comparison of two T-cell assays to evaluate T-cell responses to SARS-CoV-2 following vaccination in naïve and convalescent healthcare workers

Author: Eloise, Phillips, Sandra, Adele, Tom, Malone, Alexandra, Deeks, Lizzie, Stafford, Susan L, Dobson, Ali, Amini, Donal, Skelly, David, Eyre, Katie, Jeffery, Christopher P, Conlon, Christina, Dold, Ashley, Otter, Silvia, D'Arcangelo, Lance, Turtle, Paul, Klenerman, Eleanor, Barnes, and Dan, Wootton
Subjects: SARS-CoV-2, ChAdOx1 nCoV-19, Health Personnel, T-Lymphocytes, Immunology, Spike Glycoprotein, Coronavirus, Vaccination, Immunology and Allergy, COVID-19, Humans, Antibodies, Viral, Peptides, BNT162 Vaccine
Abstract: T-cell responses to SARS-CoV-2 following infection and vaccination are less characterized than antibody responses, due to a more complex experimental pathway. We measured T-cell responses in 108 healthcare workers (HCWs) using the commercialized Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay service (OI T-SPOT) and the PITCH ELISpot protocol established for academic research settings. Both assays detected T-cell responses to SARS-CoV-2 spike, membrane, and nucleocapsid proteins. Responses were significantly lower when reported by OI T-SPOT than by PITCH ELISpot. Four weeks after two doses of either Pfizer/BioNTech BNT162b or ChAdOx1 nCoV-19 AZD1222 vaccine, the responder rate was 63% for OI T-SPOT Panels 1 + 2 (peptides representing SARS-CoV-2 spike protein excluding regions present in seasonal coronaviruses), 69% for OI T-SPOT Panel 14 (peptides representing the entire SARS-CoV-2 spike), and 94% for the PITCH ELISpot total spike. The two OI T-SPOT panels correlated strongly with each other showing that either readout quantifies spike-specific T-cell responses, although the correlation between the OI T-SPOT panels and the PITCH ELISpot total spike was moderate. The standardization, relative scalability, and longer interval between blood acquisition and processing are advantages of the commercial OI T-SPOT assay. However, the OI T-SPOT assay measures T-cell responses at a significantly lower magnitude compared to the PITCH ELISpot assay, detecting T-cell responses in a lower proportion of vaccinees. This has implications for the reporting of low-level T-cell responses that may be observed in patient populations and for the assessment of T-cell durability after vaccination.
Published: 2022

26. The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination

Author: Philippa Matthews, David Eyre, Brent Brown, Nicole Stoesser, Koen Pouwels, Jia Wei, and John Newton
Abstract: Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single dose of ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults who received at least one vaccination, 13,404 (13.3%) had serological and/or PCR evidence of prior infection. Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations. In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose. Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.
Published: 2021

27. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Author: Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie, Hibatullah Abuelgasim, Emily Adland, Syed Adlou, Hossain Delowar Akther, Ahmed Alhussni, Mohammad Ali, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Martin Bayley, Helen Brown, Jeremy Chalk, Meera Chand, Anu Chawla, Senthil Chinnakannan, Joseph Cutteridge, Catherine de Lara, Lucy Denly, Ben Diffey, Stavros Dimitriadis, Thomas M. Drake, Timothy Donnison, Maeva Dupont, David Eyre, Alex Fairman, Siobhan Gardiner, Javier Gilbert-Jarmillo, Philip Goulder, Carl-Philipp Hackstein, Sophie Hambleton, Muzlifah Haniffa, Jenny Haworth, Jennifer Holmes, Emily Horner, Anni Jämsén, Chris Jones, Mwila Kasanyinga, Sinead Kelly, Rosemary Kirk, Michael L. Knight, Allan Lawrie, Lian Lee, Lauren Lett, Katy Lillie, Nicholas Lim, Hema Mehta, Alexander J. Mentzer, Denise O’Donnell, Ane Ogbe, Matthew Pace, Brendan A.I. Payne, Gareth Platt, Sonia Poolan, Nicholas Provine, Narayan Ramamurthy, Nichola Robinson, Leigh Romaniuk, Patpong Rongkard, Oliver L. Sampson, Beatrice Simmons, Jarmila S. Spegarova, Emily Stephenson, Kris Subramaniam, James Thaventhiran, Sarah Thomas, Simon Travis, Stephanie Tucker, Helena Turton, Adam Watson, Lisa Watson, Esme Weeks, Robert Wilson, Steven Wood, Rachel Wright, Huiyuan Xiao, Amira A.T. Zawia, and Consortium, PITCH
Subjects: Adult, Male, COVID-19 Vaccines, T-Lymphocytes, Population, Dose-Response Relationship, Immunologic, Antibodies, Viral, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, Cross-Priming, Immunity, Ethnicity, medicine, Humans, Dosing, education, Neutralizing antibody, BNT162 Vaccine, B cell, Aged, Vaccines, Synthetic, education.field_of_study, biology, SARS-CoV-2, Immunogenicity, COVID-19, Middle Aged, Reference Standards, Antibodies, Neutralizing, Regimen, Treatment Outcome, medicine.anatomical_structure, Immunoglobulin G, Immunology, Linear Models, biology.protein, Female, Antibody
Abstract: Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a sub-study of 589 individuals, we show that this single dose induces SARS-CoV-2 neutralizing antibody (NAb) responses and a sustained B and T cell response to spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by enrichment of CD4+ T cells expressing IL2. Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol., After giving a primary dose, delaying administration of a second dose of BNT162b2 COVID-19 vaccine up to 6-14 weeks continues to provide strong protection and contributes to favorable antibody, B cell, and T cell responses.
Published: 2021

28. SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study

Author: Victoria Ward, Jia Wei, William Gordon, Eleanor Barnes, Susie Dunachie, Katie Jeffery, David Eyre, and Anne-Marie O’Donnell
Subjects: Cohort Studies, SARS-CoV-2, Health Personnel, Immunoglobulin G, Antibody Formation, Vaccination, Humans, COVID-19, General Medicine, Antibodies, Viral, BNT162 Vaccine
Abstract: ObjectivesTo examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.DesignCohort study.SettingOxford University Hospitals in the United Kingdom.ParticipantsHealthcare workers who had SARS-CoV-2 serological data available and received two SARS-CoV- 2 vaccinations.Primary outcomePeak SARS-CoV-2 anti-spike IgG responses after the second vaccination and associations with underlying health conditions and the estimated risk of severe COVID-19 using an occupational health risk assessment tool.MethodsWe used univariable and multivariable linear regression models to investigate associations between antibody levels and demographics (age, sex, ethnicity), healthcare role, body mass index, underlying health conditions, vaccination status, prior infection and the Association of Local Authority Medical Advisors COVID-age risk score.Results1635 HCWs had anti-spike IgG measurements 14–84 days after second vaccination and data on any underlying health conditions. Only five HCWs (0.3%), all on immunosuppressive treatment, (including four organ transplant recipients), did not seroconvert after second vaccination. Antibody levels were independently lower with older age, diabetes, immunosuppression, respiratory disorders other than asthma and markedly so in organ transplant recipients. Levels were independently lower in ChAdOx1 versus BNT162b2 recipients and higher following previous infection. HCWs with ‘very high’ COVID-age risk scores had lower median antibody levels than those with ‘low’, ‘medium’ or ‘high’ risk scores; 4379 AU/mL, compared with 12 337 AU/mL, 9430 AU/mL and 10 524 AU/mL, respectively.ConclusionsTwo vaccine doses are effective in generating antibody responses among HCWs, including those with a high occupational risk. However, HCWs with underlying health conditions, especially diabetes, immunosuppression and organ transplant, had lower antibody levels, and vaccine response monitoring may be needed.
Published: 2022

29. Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

Author: Thomas Perkmann, Thomas Koller, Nicole Perkmann-Nagele, Maria Ozsvar-Kozma, David Eyre, Philippa Matthews, Abbie Bown, Nicole Stoesser, Marie-Kathrin Breyer, Robab Breyer-Kohansal, Otto C Burghuber, Slyvia Hartl, Daniel Aletaha, Daniela Sieghart, Peter Quehenberger, Rodrig Marculescu, Patrick Mucher, Astrid Radakovics, Miriam Klausberger, Mark Duerkop, Barba Holzer, Boris Hartmann, Robert Strassl, Gerda Leitner, Florian Grebien, Wilhelm Gerner, Reingard Grabherr, Oswald F Wagner, Christoph J Binder, and Helmuth Haslacher
Subjects: General Medicine, Pathology and Forensic Medicine
Abstract: BackgroundSerological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the ‘sensitivity improved two-test’ or ‘SIT²’ algorithm.MethodsSIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives).ResultsThe specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24–0.65) or 1.60% (0.94–2.38) at both 5% or 20% seroprevalence.ConclusionFor SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.
Published: 2022

30. Divergent trajectories of antiviral memory after SARS-Cov-2 infection

Author: Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O'Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, null Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan I de Silva, David Eyre, null Amy Flaxman, James Grist, Carl-Philipp Hackstein, null Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, null Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, null Cynthia Sedik, Laura Silva-Reyes, Holly Smith, null Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, null Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, null Christopher P. Conlon, Katie Jeffery, Simon Travis, Philip J. Goulder, John Frater, Alexander J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie
Subjects: biology, business.industry, ELISPOT, T cell, Antiviral antibody, Acquired immune system, Vaccination, Immune system, medicine.anatomical_structure, Immunity, Immunology, biology.protein, medicine, Antibody, business
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important public health implications - is not fully understood. To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination. We observed a highly variable range of responses, some of which - T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable. In such cohorts, antiviral antibody has been linked to protection against re-infection. We used integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation. These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity. Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta). Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.* These authors contributed equally.# These authors jointly supervised this work and contributed equally.Corresponding authors: Eleanor Barnes, email: ellie.barnes@ndm.ox.ac.ukand Adriana Tomic, email: 19info@adrianatomic.com
Published: 2021

31. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

Author: Erik Volz, Verity Hill, John T. McCrone, Anna Price, David Jorgensen, Áine O’Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabricia F. Nascimento, Sara M. Rey, Samuel M. Nicholls, Rachel M. Colquhoun, Ana da Silva Filipe, James Shepherd, David J. Pascall, Rajiv Shah, Natasha Jesudason, Kathy Li, Ruth Jarrett, Nicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Ian Goodfellow, Nicholas J. Loman, Oliver G. Pybus, David L. Robertson, Emma C. Thomson, Andrew Rambaut, Thomas R. Connor, Cherian Koshy, Emma Wise, Nick Cortes, Jessica Lynch, Stephen Kidd, Matilde Mori, Derek J. Fairley, Tanya Curran, James P. McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Catrin Moore, Sarah L. Caddy, Fahad A. Khokhar, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Safiah Afifi, Sian Morgan, Angela Marchbank, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Trudy Workman, William Fuller, Catherine Bresner, Luke B. Snell, Themoula Charalampous, Gaia Nebbia, Rahul Batra, Jonathan Edgeworth, Samuel C. Robson, Angela Beckett, Katie F. Loveson, David M. Aanensen, Anthony P. Underwood, Corin A. Yeats, Khalil Abudahab, Ben E.W. 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, Paul Bird, Thomas Helmer, Karlie Fallon, Christopher Holmes, Julian Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, 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, Theresa Feltwell, Charlotte J. Houldcroft, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver Pybus, Louis du Plessis, Alex Zarebski, Jayna Raghwani, Moritz Kraemer, Sarah Francois, Stephen Attwood, Tetyana Vasylyeva, M. Estee Torok, William L. Hamilton, Ian G. Goodfellow, Grant Hall, Aminu S. Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L. Pinckert, Iliana Georgana, Anna Yakovleva, Luke W. Meredith, Samuel Moses, Hannah Lowe, Felicity Ryan, Chloe L. Fisher, Ali R. Awan, John Boyes, Judith Breuer, Kathryn Ann Harris, Julianne Rose Brown, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adela Alcolea-Medina, Nathan Moore, Nicholas Cortes, Rebecca Williams, Michael R. Chapman, Lisa J. Levett, Judith Heaney, Darren L. Smith, Matthew Bashton, Gregory R. Young, John Allan, Joshua Loh, Paul A. Randell, Alison Cox, Pinglawathee Madona, Alison Holmes, Frances Bolt, James Price, Siddharth Mookerjee, Aileen Rowan, Graham P. Taylor, Manon Ragonnet-Cronin, Rob Johnson, Olivia Boyd, Erik M. Volz, Kirstyn Brunker, Katherine L. Smollett, Joshua Quick, Claire McMurray, Joanne Stockton, Sam Nicholls, Will Rowe, Radoslaw Poplawski, Rocio T. Martinez-Nunez, Jenifer Mason, Trevor I. Robinson, Elaine O'Toole, Joanne Watts, Cassie Breen, Angela Cowell, Catherine Ludden, Graciela Sluga, Nicholas W. Machin, Shazaad S.Y. Ahmad, Ryan P. George, Fenella Halstead, Venkat Sivaprakasam, James G. Shepherd, Patawee Asamaphan, Marc O. Niebel, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yasmin A. Parr, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Igor Starinskij, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Joshua B. Singer, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Yusri Taha, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer Collins, Gary Eltringham, Kate E. Templeton, Martin P. McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Reenesh Prakash, Claire Stuart, Ngozi Elumogo, Dheeraj K. Sethi, Emma J. Meader, Lindsay J. Coupland, Will Potter, Clive Graham, Edward Barton, Debra Padgett, Garren Scott, Emma Swindells, Jane Greenaway, Andrew Nelson, Wen C. Yew, Paola C. Resende Silva, Monique Andersson, Robert Shaw, Timothy Peto, Anita Justice, David Eyre, Derrick Crooke, Sarah Hoosdally, Tim J. Sloan, Nichola Duckworth, Sarah Walsh, Anoop J. Chauhan, Sharon Glaysher, Kelly Bicknell, Sarah Wyllie, Ethan Butcher, Scott Elliott, Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan T. Bradley, Elias Allara, Clare Pearson, 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, Husam Osman, Andrew Bosworth, Esther Robinson, 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, Michelle Cronin, 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, John Wain, Mark A. Webber, Alison E. Mather, David J. Baker, Steven Rudder, Muhammad Yasir, Nicholas M. Thomson, Alp Aydin, Ana P. Tedim, Gemma L. Kay, Alexander J. Trotter, Rachel A.J. Gilroy, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins, Thanh Le-Viet, Lizzie Meadows, Anastasia Kolyva, Maria Diaz, Andrew Bell, Ana Victoria Gutierrez, Ian G. Charles, Evelien M. Adriaenssens, Robert A. Kingsley, Anna Casey, David A. Simpson, Zoltan Molnar, Thomas Thompson, Erwan Acheson, Jane A.H. Masoli, Bridget A. Knight, Andrew Hattersley, Sian Ellard, Cressida Auckland, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Yann Bourgeois, Garry P. Scarlett, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Steven Liggett, Paul Baker, Sarah Essex, Ronan A. Lyons, Laura G. Caller, Sergi Castellano, Rachel J. Williams, Mark Kristiansen, Sunando Roy, Charlotte A. Williams, Patricia L. Dyal, Helena J. Tutill, Yasmin N. Panchbhaya, Leysa M. Forrest, Paola Niola, Jacqueline Findlay, Tony T. Brooks, Artemis Gavriil, Lamia Mestek-Boukhibar, Sam Weeks, Sarojini Pandey, Lisa Berry, Katie Jones, Alex Richter, Andrew Beggs, Colin P. Smith, Giselda Bucca, Andrew R. Hesketh, Ewan M. Harrison, Sharon J. Peacock, Sophie Palmer, Carol M. Churcher, Katherine L. Bellis, Sophia T. Girgis, Plamena Naydenova, Beth Blane, Sushmita Sridhar, Chris Ruis, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Leanne M. Kermack, Nazreen F. Hadjirin, Dinesh Aggarwal, Luke Griffith, Tracey Swingler, Rose K. Davidson, Thomas Williams, Carlos E. Balcazar, Michael D. Gallagher, Áine O'Toole, Stefan Rooke, Rachel Colquhoun, Jordan Ashworth, J.T. McCrone, Emily Scher, Xiaoyu Yu, 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, Dominic Kwiatkowski, 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, 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, Patrick C. McClure, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Dimitris Grammatopoulos, David Buck, John A. Todd, Angie Green, Amy Trebes, George MacIntyre-Cockett, Mariateresa de Cesare, Cordelia Langford, Alex Alderton, Roberto Amato, Sonia Goncalves, David K. Jackson, Ian Johnston, John Sillitoe, Steve Palmer, Mara Lawniczak, Matt Berriman, John Danesh, Rich Livett, Lesley Shirley, Ben Farr, Mike Quail, Scott Thurston, Naomi Park, Emma Betteridge, Danni Weldon, Scott Goodwin, Rachel Nelson, Charlotte Beaver, Laura Letchford, David A. Jackson, Luke Foulser, Liz McMinn, Liam Prestwood, Sally Kay, Leanne Kane, Matthew J. Dorman, Inigo Martincorena, Christoph Puethe, Jon-Paul Keatley, Gerry Tonkin-Hill, Christen Smith, Dorota Jamrozy, Mathew A. Beale, Minal Patel, Cristina Ariani, Michael Spencer-Chapman, Eleanor Drury, Stephanie Lo, Shavanthi Rajatileka, Carol Scott, Keith James, Sarah K. Buddenborg, Duncan J. Berger, Gaurang Patel, Maria V. Garcia-Casado, Thomas Dibling, Samantha McGuigan, Hazel A. Rogers, Adam D. Hunter, Emily Souster, Alexandra S. Neaverson, Medical Research Council (MRC), Pascall, David [0000-0002-7543-0860], and Apollo - University of Cambridge Repository
Subjects: Genome, Genetic analysis, 0302 clinical medicine, Clade, 11 Medical and Health Sciences, Genetics, 0303 health sciences, education.field_of_study, Phylogenetic tree, Virulence, C500, COG-UK Consortium, C700, Transmissibility (vibration), 3. Good health, founder effect, Spike Glycoprotein, Coronavirus, epidemiology, Viral load, Population, Glycine, B100, Genomics, Genome, Viral, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, evolution, Humans, education, 030304 developmental biology, Aspartic Acid, Whole Genome Sequencing, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2, COVID-19, spike, The COVID-19 Genomics UK Consortium, A300, 06 Biological Sciences, United Kingdom, Amino Acid Substitution, Evolutionary biology, Mutation, Biological dispersal, 030217 neurology & neurosurgery, Founder effect, Developmental Biology
Abstract: Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant., Graphical Abstract, Highlights • Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage • Phylodynamic analyses do not show significantly different growth of D614G clusters • There is no association of D614G replacement with greater severity of infection • The D614G replacement is associated with higher viral loads and younger patient age, Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.
Published: 2021

32. Community prevalence of SARS-CoV-2 in England from April to November, 2020: results from the ONS Coronavirus Infection Survey

Author: Koen B Pouwels, Thomas House, Emma Pritchard, Julie V Robotham, Paul J Birrell, Andrew Gelman, Karina-Doris Vihta, Nikola Bowers, Ian Boreham, Heledd Thomas, James Lewis, Iain Bell, John I Bell, John N Newton, Jeremy Farrar, Ian Diamond, Pete Benton, Ann Sarah Walker, Koen B. Pouwels, A. Sarah Walker, Derrick Crook, Philippa C. Matthews, Tim Peto, Nicole Stoesser, Alison Howarth, George Doherty, James Kavanagh, Kevin K. Chau, Stephanie B. Hatch, Daniel Ebner, Lucas Martins Ferreira, Thomas Christott, Brian D. Marsden, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Sarah Hoosdally, Richard Cornall, David I. Stuart, Gavin Screaton, David Eyre, John Bell, Stuart Cox, Kevin Paddon, Tim James, John N. Newton, Julie V. Robotham, Paul Birrell, Helena Jordan, Tim Sheppard, Graham Athey, Dan Moody, Leigh Curry, Pamela Brereton, Jodie Hay, Harper Vansteenhouse, Alex Lambert, Emma Rourke, Stacey Hawkes, Sarah Henry, James Scruton, Peter Stokes, Tina Thomas, John Allen, Russell Black, Heather Bovill, David Braunholtz, Dominic Brown, Sarah Collyer, Megan Crees, Colin Daglish, Byron Davies, Hannah Donnarumma, Julia Douglas-Mann, Antonio Felton, Hannah Finselbach, Eleanor Fordham, Alberta Ipser, Joe Jenkins, Joel Jones, Katherine Kent, Geeta Kerai, Lina Lloyd, Victoria Masding, Ellie Osborn, Alpi Patel, Elizabeth Pereira, Tristan Pett, Melissa Randall, Donna Reeve, Palvi Shah, Ruth Snook, Ruth Studley, Esther Sutherland, Eliza Swinn, Anna Tudor, Joshua Weston, Shayla Leib, James Tierney, Gabor Farkas, Raf Cobb, Folkert Van Galen, Lewis Compton, James Irving, John Clarke, Rachel Mullis, Lorraine Ireland, Diana Airimitoaie, Charlotte Nash, Danielle Cox, Sarah Fisher, Zoe Moore, James McLean, and Matt Kerby
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, 01 natural sciences, 03 medical and health sciences, Young Adult, 0302 clinical medicine, COVID-19 Testing, Residence Characteristics, Epidemiology, Pandemic, Credible interval, Prevalence, Medicine, Humans, Public Health Surveillance, 030212 general & internal medicine, Positive test, 0101 mathematics, Young adult, education, Child, Aged, education.field_of_study, business.industry, 010102 general mathematics, Public Health, Environmental and Occupational Health, COVID-19, Articles, Middle Aged, Health Surveys, England, Child, Preschool, Female, business, Demography
Abstract: Summary Background Decisions about the continued need for control measures to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on accurate and up-to-date information about the number of people testing positive for SARS-CoV-2 and risk factors for testing positive. Existing surveillance systems are generally not based on population samples and are not longitudinal in design. Methods Samples were collected from individuals aged 2 years and older living in private households in England that were randomly selected from address lists and previous Office for National Statistics surveys in repeated cross-sectional household surveys with additional serial sampling and longitudinal follow-up. Participants completed a questionnaire and did nose and throat self-swabs. The percentage of individuals testing positive for SARS-CoV-2 RNA was estimated over time by use of dynamic multilevel regression and poststratification, to account for potential residual non-representativeness. Potential changes in risk factors for testing positive over time were also assessed. The study is registered with the ISRCTN Registry, ISRCTN21086382. Findings Between April 26 and Nov 1, 2020, results were available from 1 191 170 samples from 280 327 individuals; 5231 samples were positive overall, from 3923 individuals. The percentage of people testing positive for SARS-CoV-2 changed substantially over time, with an initial decrease between April 26 and June 28, 2020, from 0·40% (95% credible interval 0·29–0·54) to 0·06% (0·04–0·07), followed by low levels during July and August, 2020, before substantial increases at the end of August, 2020, with percentages testing positive above 1% from the end of October, 2020. Having a patient-facing role and working outside your home were important risk factors for testing positive for SARS-CoV-2 at the end of the first wave (April 26 to June 28, 2020), but not in the second wave (from the end of August to Nov 1, 2020). Age (young adults, particularly those aged 17–24 years) was an important initial driver of increased positivity rates in the second wave. For example, the estimated percentage of individuals testing positive was more than six times higher in those aged 17–24 years than in those aged 70 years or older at the end of September, 2020. A substantial proportion of infections were in individuals not reporting symptoms around their positive test (45–68%, dependent on calendar time. Interpretation Important risk factors for testing positive for SARS-CoV-2 varied substantially between the part of the first wave that was captured by the study (April to June, 2020) and the first part of the second wave of increased positivity rates (end of August to Nov 1, 2020), and a substantial proportion of infections were in individuals not reporting symptoms, indicating that continued monitoring for SARS-CoV-2 in the community will be important for managing the COVID-19 pandemic moving forwards. Funding Department of Health and Social Care.
Published: 2021
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33. Osteogenesis imperfecta tooth level phenotype analysis: Cross-sectional study

Author: Doaa Taqi, Hanan Moussa, Timothy Schwinghamer, Maxime Ducret, Didem Dagdeviren, Jean-Marc Retrouvey, Frank Rauch, Faleh Tamimi, Brendan Lee, V. Reid Sutton, Sandesh C.S. Nagamani, Francis Glorieux, Janice Lee, Paul Esposito, Maegen Wallace, Michael Bober, David Eyre, Danielle Gomez, Gerald Harris, Tracy Hart, Mahim Jain, Deborah Krakow, Jeffrey Krischer, Eric Orwoll, Lindsey Nicol, Cathleen Raggio, Peter Smith, and Laura Tosi
Subjects: 0301 basic medicine, Histology, Taurodontism, Physiology, Endocrinology, Diabetes and Metabolism, Dentistry, Oral medicine, 030209 endocrinology & metabolism, Article, Tooth discoloration, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Dentinogenesis Imperfecta, Dentin, medicine, Humans, Enamel paint, business.industry, Dentinogenesis, Tooth abnormalities, Osteogenesis Imperfecta, medicine.disease, stomatognathic diseases, Cross-Sectional Studies, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Osteogenesis imperfecta, visual_art, visual_art.visual_art_medium, Pulp (tooth), Connective tissue, Malocclusion, business, Tooth
Abstract: INTRODUCTION: Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp obliteration (calcified dental pulp space), and taurodontism (enlarged dental pulp space) vary between and within patients. To better understand the associations and variations in these anomalies, a cross-sectional study was designed to analyze the dental phenotype in OI patients at the individual tooth type. METHOD: A cohort of 171 individuals with OI type I, III and IV, aged 3–55 years, were recruited and evaluated for tooth discoloration, pulp obliteration, and taurodontism at the individual tooth level, using intraoral photographs and panoramic radiographs. RESULTS: Genetic variants were identified in 154 of the participants. Patients with Helical α1 and α2 glycine substitutions presented the highest prevalence of tooth discoloration, while those with α1 Haploinsufficiency had the lowest (
Published: 2021

34. Genetic relatedness of ceftriaxone-resistant and high-level azithromycin resistant

Author: Amy V, Jennison, David, Whiley, Monica M, Lahra, Rikki M, Graham, Michelle J, Cole, Gwenda, Hughes, Helen, Fifer, Monique, Andersson, Anne, Edwards, and David, Eyre
Subjects: Adult, Male, whole genome sequencing, Genotype, Ceftriaxone, Australia, Microbial Sensitivity Tests, Azithromycin, Polymorphism, Single Nucleotide, Neisseria gonorrhoeae, United Kingdom, Anti-Bacterial Agents, microbial drug resistance, Gonorrhea, PCR, Drug Resistance, Bacterial, Humans, XDR, AMR, antimicrobial resistance, Sentinel Surveillance, Phylogeny, Rapid Communication
Abstract: Between February and April 2018, three ceftriaxone-resistant and high-level azithromycin-resistant Neisseria gonorrhoeae cases were identified; one in the United Kingdom and two in Australia. Whole genome sequencing was used to show that the isolates from these cases belong to a single gonococcal clone, which we name the A2543 clone.
Published: 2019

35. Malocclusion traits and oral health–related quality of life in children with osteogenesis imperfecta

Author: Mohammadamin Najirad, Sreenath Arekunnath Madathil, Frank Rauch, V. Reid Sutton, Brendan Lee, Jean-Marc Retrouvey, Shahrokh Esfandiari, Sandesh C.S. Nagamani, Francis Glorieux, Paul Esposito, Maegen Wallace, Michael B. Bober, David Eyre, Danielle Gomez, Gerald Harris, Tracy Hart, Mahim Jain, Deborah Krakow, Jeffrey Krischer, Eric Orwoll, Lindsey Nicol, Cathleen Raggio, Peter Smith, and Laura Tosi
Subjects: education.field_of_study, Cross-sectional study, business.industry, Incidence (epidemiology), Population, Dentistry, 030206 dentistry, Odds ratio, medicine.disease, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Osteogenesis imperfecta, medicine, Malocclusion, education, business, General Dentistry
Abstract: Background The incidence of malocclusion is higher among people with osteogenesis imperfecta (OI) than the general population, and treatment options are limited due to the weak structure of bones and teeth. Focusing on those malocclusion traits that might have a high impact on a patient’s oral health–related quality of life (OHRQoL) is warranted. Methods A total of 138 children and adolescents with OI were examined for malocclusion traits. OHRQoL was measured using age-specific versions (8 through 10 years and 11 through 14 years) of the Child Perceptions Questionnaire (CPQ), considering the following domains: oral symptoms, functional limitation, emotional well-being, and social well-being. Higher scores implied worse OHRQoL. Multivariable ordinal logistic regression was used to estimate the association between malocclusion traits and OHRQoL. Results Among children aged 8 through 10 years (n = 56), the CPQ and its constituent domain scores were relatively similar between those with malocclusion (higher scores) and those without. In the adolescent (n = 82) group aged 11 through 14 years; however, those with posterior crossbite (odds ratio, 5.01; 95% confidence interval, 1.40 to 12.41) or open bite (odds ratio, 3.21; 95% confidence interval, 1.21 to 10.23) experienced statistically significantly higher degrees of functional limitations (a higher functional limitation score) than those without. Conclusions Adolescents with OI and posterior open bites or crossbites have substantial self-reported functional limitations and worse oral symptoms, which warrants additional investigation and therapeutic trials in an attempt to improve the malocclusion. In addition, the authors found that the CPQ can be a useful tool in a clinical trial of orthodontic interventions in OI.
Published: 2020

36. Glainne : (Glass)

Author: David Eyre and David Eyre
Abstract: Sarah Campbell is a young woman doing well. A teaching job in a good school. A handsome partner. But a sudden memory from her student days forces Sarah to ask some uncomfortable questions about herself, her past and her future.
Published: 2015

37. Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone

Author: Caressa D, Lietman, Joohyun, Lim, Ingo, Grafe, Yuqing, Chen, Hao, Ding, Xiaohong, Bi, Catherine G, Ambrose, Nadja, Fratzl-Zelman, Paul, Roschger, Klaus, Klaushofer, Wolfgang, Wagermaier, Ingo, Schmidt, Peter, Fratzl, Jyoti, Rai, MaryAnn, Weis, David, Eyre, Douglas R, Keene, Deborah, Krakow, and Brendan H, Lee
Subjects: Male, Mice, Knockout, Osteoblasts, Organ Size, X-Ray Microtomography, Spectrum Analysis, Raman, Bone and Bones, Article, Biomechanical Phenomena, Mice, Inbred C57BL, Tacrolimus Binding Proteins, Calcification, Physiologic, Cross-Linking Reagents, Animals, Newborn, Bone Density, Animals, Female, Amino Acid Sequence, Collagen, Crystallization, Gene Deletion
Abstract: Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast specific Col1a1 2.3kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small angle x-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton.
Published: 2016

38. Mathematically modeling PCR: An asymptotic approximation with potential for optimization

Author: David Eyre, James A. Powell, Thomas Robbins, and Martha J. Garlick
Subjects: Optimal design, Quantitative Biology::Biomolecules, DNA, Complementary, Dynamical systems theory, Differential equation, Applied Mathematics, Mathematical analysis, General Medicine, Polymerase Chain Reaction, Quantitative Biology::Genomics, Minimax approximation algorithm, Law of mass action, Computational Mathematics, Models, Chemical, Approximation error, Modeling and Simulation, Asymptotology, Applied mathematics, Taq Polymerase, General Agricultural and Biological Sciences, Asymptotic expansion, DNA Primers, Mathematics
Abstract: A mathematical model for PCR (Polymerase Chain Reaction) is developed using the law of mass action and simplifying assumptions regarding the structure of the reactions. Differential equations are written from the chemical equations, preserving the detail of the complementary DNA single strand being extended one base pair at a time. The equations for the annealing stage are solved analytically. The method of multiple scales is used to approximate solutions for the extension stage, and a map is developed from the solutions to simulate PCR. The map recreates observed PCR well, and gives us the ability to optimize the PCR process. Our results suggest that dynamically optimizing the extension and annealing stages of individual samples may significantly reduce the total time for a PCR run. Moreover, we present a nearly optimal design that functions almost as well and does not depend on the specifics of a single reaction, and so would work for multi sample and multiplex applications.
Published: 2010

39. A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation

Author: Caressa D, Lietman, Ronit, Marom, Elda, Munivez, Terry K, Bertin, Ming-Ming, Jiang, Yuqing, Chen, Brian, Dawson, Mary Ann, Weis, David, Eyre, and Brendan, Lee
Subjects: Mice, Mutation, Animals, Membrane Proteins, Mice, Transgenic, Article
Abstract: Osteogenesis imperfecta (OI) type V is characterized by increased bone fragility, long bone deformities, hyperplastic callus formation, and calcification of interosseous membranes. It is caused by a recurrent mutation in the 5' UTR of the IFITM5 gene (c.-14C T). This mutation introduces an alternative start codon, adding 5 amino acid residues to the N-terminus of the protein. The mechanism whereby this novel IFITM5 protein causes OI type V is yet to be defined. To address this, we created transgenic mice expressing either the wild-type or the OI type V mutant IFITM5 under the control of an osteoblast-specific Col1a1 2.3-kb promoter. These mutant IFITM5 transgenic mice exhibited perinatal lethality, whereas wild-type IFITM5 transgenic mice showed normal growth and development. Skeletal preparations and radiographs performed on E15.5 and E18.5 OI type V transgenic embryos revealed delayed/abnormal mineralization and skeletal defects, including abnormal rib cage formation, long bone deformities, and fractures. Primary osteoblast cultures, derived from mutant mice calvaria at E18.5, showed decreased mineralization by Alizarin red staining, and RNA isolated from calvaria showed reduced expression of osteoblast differentiation markers such as Osteocalcin, compared with nontransgenic littermates and wild-type mice calvaria, consistent with the in vivo phenotype. Importantly, overexpression of wild-type Ifitm5 did not manifest a significant bone phenotype. Collectively, our results suggest that expression of mutant IFITM5 causes abnormal skeletal development, low bone mass, and abnormal osteoblast differentiation. Given that neither overexpression of the wild-type Ifitm5, as shown in our model, nor knock-out of Ifitm5, as previously published, showed significant bone abnormalities, we conclude that the IFITM5 mutation in OI type V acts in a neomorphic fashion.
Published: 2014

40. Biochemical markers of bone turnover in lactating and nonlactating postpartum women

Author: Brahm Shapiro, Mary Crutchfield, Mary Jannausch, David Eyre, John F. Randolph, MaryFran Sowers, and Bruce W. Hollis
Subjects: Adult, medicine.medical_specialty, Time Factors, Bone density, Endocrinology, Diabetes and Metabolism, Osteocalcin, Clinical Biochemistry, Population, Biochemistry, Collagen Type I, Statistics, Nonparametric, Bone remodeling, Endocrinology, Bone Density, Lactation, Internal medicine, medicine, Humans, Longitudinal Studies, Bone Resorption, education, Femoral neck, education.field_of_study, Bone Development, business.industry, Postpartum Period, Biochemistry (medical), Age Factors, Environmental exposure, Alkaline Phosphatase, Calcium, Dietary, Breast Feeding, medicine.anatomical_structure, Female, Collagen, Peptides, business, Breast feeding, Biomarkers, Postpartum period
Abstract: We measured two bone-formation markers, osteocalcin and bone-specific alkaline phosphatase, and one bone-resorption marker, N-telopeptide, in a longitudinal study in order to describe levels of these markers in lactating and nonlactating women after parturition. This 18-month postpartum period included an initial 6 months in which a 5% short-term bone loss occurred at both spine and femoral neck among breast-feeding women. The second part of the 18-month period was characterized by bone recovery among women who had lost bone. These bone-change characteristics provided an opportunity to evaluate the performance of biochemical markers during both bone loss and recovery and to identify environmental exposures during lactation associated with bone turnover. The eligible population comprised 115 women whose bone-turnover markers were measured at 2 weeks (baseline) and at 2, 4, 6, 12, and 18 months after parturition. Participants reported reproductive characteristics, diet, physical activity, use of medications, and infant-feeding practices at each contact. Women were grouped according to lactation duration: 0-1 months, 2-5 months, and 6 months or more. Women who breast-fed for at least 6 months had significantly different levels of all three bone-turnover markers compared with the levels in bottle-feeding controls, which were indicative of substantially increased bone turnover. Factors that predicted the difference in biochemical markers from baseline to 6-month values by regression analysis were lactation of 2-6 months duration and lactation for 6 months or more. Dietary calcium intake, physical activity level, and body size did not explain the differences in the change from the baseline level to the 6-month level, a period of time that corresponded with bone loss in the lactating women. Factors that predicted the differences in bone-turnover markers between 6 and 18 months (the time of bone-mass recovery) were lactation status and number of months to resumption of menses. By the 18-month observation, there was no difference in the mean values for the measured bone-turnover markers among the three lactation groups. This suggests that menstrual activity, rather than diet or physical activity, is the primary factor in bone-mass recovery after the bone loss of lactation.
Published: 1995

41. Solving dynamic equations for the size distribution of supported metal catalysts

Author: C. J. Wright, David Eyre, and Raymond C. Everson
Subjects: Coalescence (physics), Partial differential equation, Kernel method, Chemistry, Particle-size distribution, Initial value problem, Sintering, Crystallite, Statistical physics, Physical and Theoretical Chemistry, Similarity solution, Catalysis
Abstract: A simple kinetic model for the growth of catalytic metal crystallites on a support is investigated. Results for an exactly solvable coalescence model with initial condition consistent with experiment shows that the similarity solution does not provide an accurate description of the particle size distribution. A numerical solution of the kinetic equation is shown to be in excellent agreement with experimental data. The model can be used to provide useful information concerning the underlying mechanism responsible for sintering.
Published: 1991

42. Condensin binding at distinct and specific chromosomal sites in the Saccharomyces cerevisiae genome

Author: Bi-Dar Wang, Munira A. Basrai, David Eyre, Alexander V. Strunnikov, and Michael Lichten
Subjects: Chromatin Immunoprecipitation, Saccharomyces cerevisiae Proteins, Genotype, Heterochromatin, Condensin, Mitosis, macromolecular substances, Saccharomyces cerevisiae, Chromosome Structure and Dynamics, Biology, Chromosomes, Mitotic chromosome condensation, Condensin complex, Open Reading Frames, Species Specificity, Centromere, Molecular Biology, Oligonucleotide Array Sequence Analysis, Genetics, Adenosine Triphosphatases, Binding Sites, Models, Genetic, Nucleotides, Cell Cycle, Nuclear Proteins, Nucleic Acid Hybridization, Cell Biology, DNA, Chromatin, DNA-Binding Proteins, RNA, Ribosomal, Multiprotein Complexes, biology.protein, Chromosomes, Fungal, Genome, Fungal, Chromatin immunoprecipitation, Protein Binding
Abstract: Mitotic chromosome condensation is chiefly driven by the condensin complex. The specific recognition (targeting) of chromosomal sites by condensin is an important component of its in vivo activity. We previously identified the rRNA gene cluster in Saccharomyces cerevisiae as an important condensin-binding site, but both genetic and cell biology data suggested that condensin also acts elsewhere. In order to characterize the genomic distribution of condensin-binding sites and to assess the specificity of condensin targeting, we analyzed condensin-bound sites using chromatin immunoprecipitation and hybridization to whole-genome microarrays. The genomic condensin-binding map shows preferential binding sites over the length of every chromosome. This analysis and quantitative PCR validation confirmed condensin-occupied sites across the genome and in the specialized chromatin regions: near centromeres and telomeres and in heterochromatic regions. Condensin sites were also enriched in the zones of converging DNA replication. Comparison of condensin binding in cells arrested in G(1) and mitosis revealed a cell cycle dependence of condensin binding at some sites. In mitotic cells, condensin was depleted at some sites while enriched at rRNA gene cluster, subtelomeric, and pericentromeric regions.
Published: 2005

43. Prisoner Escort in Scotland: Costs, Projection and Performance under Scrutiny

Author: David Eyre and Sheila Bird
Subjects: Statistics and Probability, Scrutiny, Projection (mathematics), Context (language use), Sociology, Law and economics
Abstract: David Eyre is a journalist. He says that he is a little ignorant when it comes to statistics, as he thinks many people in the media are. Which is pretty surprising when you consider the number of stories that are based on statistics—everything from crime surveys to NHS waiting lists. Here he and Sheila Bird describe how they sought to address this problem in the context of prisoner escort in Scotland.
Published: 2005

44. Pathogenesis/Homeostasis

Author: David Eyre and David J Schurman
Subjects: Orthopedics and Sports Medicine, Surgery, General Medicine
Published: 2004

45. Anthropometrics and Biochemical Markers in Men.

Author: Oana Donescu, Michele Battié, Tapio Videman, Juha Risteli, and David Eyre
Subjects: ANTHROPOMETRY, BIOMARKERS, METABOLISM, BIOCHEMISTRY
Abstract: The relation between anthropometric components and biochemical markers has not been previously studied. Toclarify the role of anthropometric factors in bone metabolism in men, 145 randomly selected subjects 40 to 70 yr ofage from a population-based cohort were studied. Pearson's r and multiple regression analysis were used to assess therelation between anthropometrics (weight, body mass index [BMI], percentage of body fat, fat-free weight, and fatfreeBMI), biochemical markers, and bone mineral density (BMD) at the spine and femoral neck, as well as betweenBMD and each biochemical marker (serum bone formation marker procollagen amino-terminal propeptide [PINP],urinary bone resorption marker amino-terminal telopeptide [NTx], and the ratio of PINP to NTx. Of the anthropometricfactors, fat-free BMI had the highest association with the markers (r = -0.21 to -0.35, p < 0.05) and explaineda higher percent of both spine BMD and NTx variance than weight. Body fat did not correlate with the BMD measures.Urinary NTx was a better indicator of current BMD status than PINP or the ratio of PINP to NTx, with thehighest association with BMD at the sites tested (r = -0.20 to -0.29). NTx levels were statistically significantly differentbetween men with normal and osteoporotic BMD at the femoral neck. [ABSTRACT FROM AUTHOR]
Published: 2005
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46. Ocean acidification offsets the effect of warming on sediment denitrification and associated nitrous oxide production

Author: Michelle Nicole Simone, Dirk Vincent Erler, Kai Georg Schulz, Joanne Margaret Oakes, and Bradley David Eyre
Subjects: Geology, QE1-996.5, Environmental sciences, GE1-350
Abstract: Abstract Rates of denitrification and associated nitrous oxide (N2O) production are expected to increase with global warming, leading to positive climate feedback. However, previous studies have not considered the combined effect of ocean acidification (OA, pCO2 ~ 900 µatm) and warming on denitrification rates and N2O production. Here we used a series of whole core incubation studies to assess the combined impact of warming and OA on estuarine sediment denitrification rates and N2O production. Strong warming (+5 °C over mean in situ conditions) increased N2O production by ~4.2 µmol-N m−2 d−1 and denitrification by ~43 µmol-N m−2 d−1, fuelled by water column nitrate (Dw), but decreased rates of nitrification-coupled denitrification in the sediment (Dn) by ~82 µmol-N m−2 d−1. While Dn was not affected by OA, Dw decreased significantly by 51 µmol-N m−2 d−1 when OA was coupled with warmer temperatures. We estimate that OA may offset the increase in estuarine sediment denitrification and N2O production expected from warming alone by up to 64% and reduce a potential positive climate feedback loop by inhibiting denitrification pathways.
Published: 2024
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47. Type XI or 1α2α3α Collagen

Author: David Eyre and Jiann-Jiu Wu
Subjects: Collagen, type I, alpha 1, Chemistry, Molecular biology
Published: 1987

48. DOP20 Functional viral neutralisation responses after SARS-CoV-2 infection in Inflammatory Bowel Disease patients receiving infusion therapies: Report from the ICARUS-IBD Consortium

Author: Wellens J, Edmans M, Obolski U, Marlow L, Brann S, Dunachie S, David Eyre, Helmus D, Barnes E, Colombel J, Wong S, Klenerman P, Lindsay J, Thompson C, and Satsangi J
Subjects: Gastroenterology, General Medicine
Abstract: Background Recent data have highlighted adverse clinical outcomes in IBD patients treated with infliximab/thiopurines (IFX/THIO) upon infection with SARS-CoV-2, as well as attenuated serological responses after infection and vaccination in patients treated with IFX. To provide mechanistic insight, we explored the serological and functional anti-viral response after infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to healthy controls to guide clinical decision-making regarding treatment and vaccination strategies. Methods Serum from 640 IBD patients attending routine infusions in Oxford and London in May to December 2020 was screened for anti-SARS-CoV-2 antibody responses by the Abbott assay. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type strain receptor-binding domain (RBD), full-length spike, and nucleocapsid was assayed by IgG/IgA ELISA over time as well as by IgG high-throughput MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralising antibodies to the wild type, and an ELISA-based inhibition assay to compare differential inhibition of the wild type vs. delta variant SARS-CoV-2 RBD-ACE2 interaction. Results All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls for all SARS-CoV-2 antigens, using MSD V-PLEX ELISA (Figure 1). The greatest reduction in IgG response by ELISA was observed in individuals treated with IFX/THIO (p=0.00019), whereas IgG response over time declined significantly faster in the IFX treated group (p=0.019). IgA responses were significantly reduced in the IFX/THIO group compared to healthy controls (p=0.009), but not in the IFX or VDZ monotherapy group. The rate of decline in these monotherapy groups was also not significantly different to healthy controls. Functional SARS-CoV-2 neutralisation was significantly lower in all IBD patients compared to healthy controls, with the greatest reduction in patients receiving IFX/THIO (Figure 2A; p=0.00000091). The delta variant inhibition capacity was significantly reduced in 68.1% of IBD patients (30/44, Figure 2B; p=0.0005). Conclusion IFX/THIO is associated with significantly lower IgA and IgG responses, and with impaired functional SARS-CoV-2 neutralising antibody capacity, compared to healthy individuals. Whilst IgG and neutralisation responses are reduced in each group of IBD patients, these findings were most pronounced in the combination treatment group. As neutralising antibody responses are associated with protection, this observation may impact on decision-making regarding treatment and vaccination/antiviral strategies.

49. Human-mouse interspecies collagen I heterotrimer is functional during embryonic development of Mov13 mutant mouse embryos

Author: Hong Wu, John F. Bateman, Angelika Schnieke, Arlene Sharpe, Douglas Barker, Thomas Mascara, David Eyre, Romaine Bruns, Paul Krimpenfort, Anton Berns, and Rudolf Jaenisch
Subjects: Genetically modified mouse, Macromolecular Substances, Transgene, Mutant, Mice, Transgenic, Biology, medicine.disease_cause, Bone and Bones, Mice, Gene expression, medicine, Animals, Humans, Molecular Biology, Gene, Skin, Mutation, DNA, Cell Biology, Blotting, Northern, Embryo, Mammalian, Phenotype, Molecular biology, Mice, Mutant Strains, Blot, Genes, RNA, Genes, Lethal, Collagen, Procollagen, Research Article
Abstract: To investigate whether the human pro alpha 1(I) collagen chain could form an in vivo functional interspecies heterotrimer with the mouse pro alpha 2(I) collagen chain, we introduced the human COL1A1 gene into Mov13 mice which have a functional deletion of the endogenous COL1A1 gene. Transgenic mouse strains (HucI and HucII) carrying the human COL1A1 gene were first generated by microinjecting the COL1A1 gene into wild-type mouse embryos. Genetic evidence indicated that the transgene in the HucI strain was closely linked to the endogenous mouse COL1A1 gene and was X linked in the HucII transgenic strain. Northern (RNA) blot and S1 protection analyses showed that the transgene was expressed in the appropriate tissue-specific manner and as efficiently as the endogenous COL1A1 gene. HucII mice were crossed with Mov13 mice to transfer the human transgene into the mutant strain. Whereas homozygous Mov13 embryos die between days 13 and 14 of gestation, the presence of the transgene permitted apparently normal development of the mutant embryos to birth. This indicated that the mouse-human interspecies collagen I heterotrimer was functional in the animal. The rescue was, however, only partial, as all homozygotes died within 36 h after delivery, with signs of internal bleeding. This could have been due to a functional defect in the interspecies hybrid collagen. Extensive analysis failed to reveal any biochemical or morphological abnormalities of the collagen I molecules in Mov13-HucII embryos. This may indicate that there was a subtle functional defect of the interspecies hybrid protein which was not revealed by our analysis or that another gene has been mutated by the retroviral insertion in the Mov13 mutant strain.

50. Biology of Invertebrate and Lower Vertebrate Collagens. Proceedings of a Workshop Held June 24-28, 1984, at the Alessandro Volta Center for Scientific Culture, Villa Olmo, Como, Italy. A. Bairati , R. Garrone

Author: David Eyre
Subjects: Scientific culture, Anthropology, Center (algebra and category theory), Environmental ethics, General Agricultural and Biological Sciences, Invertebrate
Published: 1986

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