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2. Parvovirus B19 induced acute severe anaemia in a well-controlled HIV-positive individual

Author

Thomas Swaine, Niall Ahmad, Aula Abbara, Borja Mora-Peris, Melissa Wickremasinghe, Christopher Lambert, Anas Khan, and Paul Randell

Subjects
Parvovirus B19, HIV, IVIG, Anaemia, Pure red cell aplasia, Transient aplastic crisis, Infectious and parasitic diseases, RC109-216
Abstract

Background: We describe the unusual case of a parvovirus B19 (PB19) infection inducing a severe acute aplastic anaemia with secondary multiorgan dysfunction in the context of well-controlled HIV and the absence of an underlying chronic haemolytic disorder. Treatment with intravenous immunoglobulin therapy (IVIG) was also required in this case due to persisting reticulocytopaenia, seemingly at odds with established descriptions of PB19 related anaemic syndromes as either chronic Pure Red Cell Aplasia or acute Transient Aplastic Crises. Case presentation: A 25-year-old Brazilian male tourist living with well-controlled HIV and undetectable HIV viral load presented in extremis with multiorgan dysfunction after a 5-day history of non-specific illness. Investigation for PB19 confirmed a positive IgM, weakly positive IgG, and significant PB19 viraemia. He received initial supportive management with blood products and was later given two doses of 1 g/kg immunoglobulin therapy for persistent reticulocytopaenia. He was able to be discharged to his country of origin and reported no subsequent relapse at follow up at one year. Conclusions: Severe PB19 infections remain a rare but significant phenomenon amongst patients living with HIV even in the context of adherence to effective antiretroviral therapy, and it appears hyperacute presentations are possible even without underlying chronic haemolytic disorders. Though there is a dearth of contemporary practice managing these infections, treatment with IVIG remains a cornerstone therapy in these instances where ART alone is not sufficient to resolve reticulocytopaenia.

Published
2024
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3. Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation

Author

Scott J. C. Pallett, Joseph Heskin, Fergus Keating, Andrea Mazzella, Hannah Taylor, Aatish Patel, Georgia Lamb, Deborah Sturdy, Natalie Eisler, Sarah Denny, Esmita Charani, Paul Randell, Nabeela Mughal, Eleanor Parker, Carolina Rosadas de Oliveira, Michael Rayment, Rachael Jones, Richard Tedder, Myra McClure, Elisabetta Groppelli, Gary W. Davies, Matthew K. O’Shea, and Luke S. P. Moore

Subjects
Medicine
Abstract

Abstract Background Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies. Methods A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. Results Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8–14.5) higher associated with hybrid immunity (p 100BAU/ml), show inhibition

Published
2023
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4. Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies

Author

Lucy B. Cook, Gillian O’Dell, Eleni Vourvou, Renuka Palanicawandar, Sasha Marks, Dragana Milojkovic, Jane F. Apperley, Sandra Loaiza, Simone Claudiani, Marco Bua, Catherine Hockings, Donald Macdonald, Aris Chaidos, Jiri Pavlu, Nichola Cooper, Sarah Fidler, Paul Randell, and Andrew J. Innes

Subjects
Science
Abstract

SARS-CoV-2 vaccination has shown reduced efficacy in patients with haematological malignancies. Here, the authors show that a third vaccine is able to enhance SARS-CoV-2 antibody responses in most cases in a cohort of 381 patients with haematological malignancies.

Published
2022
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6. Descriptive comparison of admission characteristics between pandemic waves and multivariable analysis of the association of the Alpha variant (B.1.1.7 lineage) of SARS-CoV-2 with disease severity in inner London

Author

Keith Morris, Judith Breuer, NgeeKeong Tan, Eric Witele, Sophie Hunter, Monica Panca, Aleks Marek, Paul Flowers, Gaia Nebbia, Sam Haldenby, Jacqui Prieto, Gee Yen Shin, Fiona Mapp, Andrew Copas, Mark Hopkins, Oliver Stirrup, Adam Witney, Kenneth Laing, May Rabuya, Vasa Curcin, Alison Holmes, Mohammad Raza, Wenjuan Wang, Rachel Williams, David Robertson, Julie Samuel, Rory Gunson, Helen Wheeler, Alexander J Keeley, Paul Randell, Cariad Evans, Tabassum Khan, Michelle Ramsay, Darren Smith, James Price, Sarah Francis, Shazaad Ahmad, Finola Higgins, Eleni Nastouli, Abhinav Kumar, Katie Johnson, Sharon Glaysher, Scott Elliott, Rebecca Gregory, Matthew D Parker, Helen Umpleby, Emanuela Pelosi, Emma Thomson, Anna Riddell, Yanzhong Wang, David Harrington, Alexandra Bailey, Nikunj Mahida, Charlotte Williams, Tanzina Haque, David G Partridge, Yusri Taha, Adrienn Angyal, Catherine Houlihan, James Shepherd, Hayley Colton, Chris Davis, Adela Alcolea-Medina, Themoula Charalampous, Beatrix Kele, Irene Monahan, Guy Mollett, Sunando Roy, Joshua Taylor, Sophie Weller, Eleri Wilson-Davies, Joseph Hughes, Tabitha Mahungu, Cassie Pope, Samuel Robson, Kordo Saeed, Luke Snell, James Blackstone, Leanne Hockey, Georgia Marley, Christine Peters, Flavia Flaviani, Bindi Patel, Rahul Batra, Jennifer Hart, Nadua Bayzid, Marius Cotic, Luke Green, Amy State, Alison Cope, Peijun Zhang, Max Whiteley, Marta Gallis Ramalho, Stella Christou, Paige Wolverson, Joe Heffer, Nikki Smith, Salman Goudarzi, Kate Cook, Katie Loveson, Buddhini Samaraweera, Stephen Aplin, Sarah Jeremiah, Matthew Harvey, Thea Sass, Dan Frampton, Matt Byott, Judith Heaney, Ana da Silva Filipe, Thushan de Silva, Jonathan Edgeworth, Luke B Snell, Leonardo de Jongh, Teresa Cutino-Moguel, Raghavendran Kulasegaran-Shylini, Claire E. Broad, Dola Owoyemi, Clare Coffey, Martina Cummins, Tyrra D’Souza, Emily Goldstein, Emilie Shepherd, Katherine Smollett, Alice Broos, Stephen Carmichael, Nicholas Suarez, Sreenu Vattipally, Ioulia Tsatsani, Jacqueline McTaggart, Stephanie McEnhill, Adela Medina, Jörg Saßmannshausen, Sulekha Gurung, Anu Augustine, Sid Mookerjee, Krystal Johnson, Thilipan Thaventhiran, Damien Mine, Isa Ahmad, Anitha Ramanathan, Anu Chawla, Alistair Derby, Becky Taylor, Charles Numbere, Jenifer Mason, Nicholas Machin, Julie Cawthorne, Ryan George, James Montgomery, Deborah McKew, Angela Cobb, Maria Leader, Shirelle Burton-Fanning, Lydia Taylor, Matthew Bashton, Matthew Crown, Matthew Loose, Patrick McClure, Mitch Clarke, Elaine Baxter, Carl Yates, Irfan Aslam, Vicki Fleming, Michelle Lister, Johnny Debebe, Nadine Holmes, Christopher Moore, Matt Carlile, Dianne Irish-Tavares, Mia De Mesa, Vicky Pang, Jelena Heaphy, Wendy Chatterton, Monika Pusok, Tranprit Saluja, Zahira Maqsood, Angie Williams, Debbie Devonport, Lucy Palinkas, Diane Thomlinson, Julie Booth, Ashok Dadrah, Amanda Symonds, Cassandra Craig, Benjamin B Lindsey, Benjamin H Foulkes, Stavroula F Louka, Phillip Ravencroft, Sharon Hsu, Nasar Ali, Rasha Raghei, Samantha E Hansford, Hailey R Hornsby, Phil Wade, Kay Cawthron, Maqsood Khan, Amber Ford, Imogen Wilson, Kate Harrington, Nic Tinker, Sally Nyinza, Adhyana Mahanama, Siona Silviera, Christopher Fearn, Claudia Cardosa Pereira, Vaz Malik, Gema Martinez-Garcia, Leila Hail, Ndifreke Atang, Helen Francis, Milica Rajkov, Rachel McComish, Alyson MacNeil, Alif Tamuri, and Stefan Piatek

Subjects
Medicine
Published
2022
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7. Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients.

Author

Andrew I Ritchie, Owais Kadwani, Dina Saleh, Behrad Baharlo, Lesley R Broomhead, Paul Randell, Umeer Waheed, Maie Templeton, Elizabeth Brown, Richard Stümpfle, Parind Patel, Stephen J Brett, and Sanooj Soni

Subjects
Medicine, Science
Abstract

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p

Published
2022
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8. Tracking the incidence and risk factors for SARS-CoV-2 infection using historical maternal booking serum samples.

Author

Edward Mullins, Ruth McCabe, Sheila M Bird, Paul Randell, Marcus J Pond, Lesley Regan, Eleanor Parker, Myra McClure, and Christl A Donnelly

Subjects
Medicine, Science
Abstract

The early transmission dynamics of SARS-CoV-2 in the UK are unknown but their investigation is critical to aid future pandemic planning. We tested over 11,000 anonymised, stored historic antenatal serum samples, given at two north-west London NHS trusts in 2019 and 2020, for total antibody to SARS-CoV-2 receptor binding domain (anti-RBD). Estimated prevalence of seroreactivity increased from 1% prior to mid-February 2020 to 17% in September 2020. Our results show higher prevalence of seroreactivity to SARS-CoV-2 in younger, non-white ethnicity, and more deprived groups. We found no significant interaction between the effects of ethnicity and deprivation. Derived from prevalence, the estimated incidence of seroreactivity reflects the trends observed in daily hospitalisations and deaths in London that followed 10 and 13 days later, respectively. We quantified community transmission of SARS-CoV-2 in London, which peaked in late March / early April 2020 with no evidence of community transmission until after January 2020. Our study was not able to determine the date of introduction of the SARS-CoV-2 virus but demonstrates the value of stored antenatal serum samples as a resource for serosurveillance during future outbreaks.

Published
2022
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9. A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics

Author

Michael A. Crone, Miles Priestman, Marta Ciechonska, Kirsten Jensen, David J. Sharp, Arthi Anand, Paul Randell, Marko Storch, and Paul S. Freemont

Subjects
Science
Abstract

The SARS-CoV-2 pandemic has created large demand on global testing capability. Here the authors use the London Biofoundry, an automated synthetic biology platform, and develop an open-source virus-like particle to implement high-throughput diagnostics.

Published
2020
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10. SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study

Author

Judith Breuer, Catherine F Houlihan, David Partridge, Gaia Nebbia, Jacqui Prieto, Gee Yen Shin, Oliver Stirrup, Kenneth Laing, Rachel Williams, Helen Wheeler, Paul Randell, Ana da Silva Filipe, Tommy Rampling, Tabassum Khan, James Price, Sharon Glaysher, Scott Elliott, Helen Umpleby, Emanuela Pelosi, Emma Thomson, Cristina Venturini, Anna Riddell, Alison Cox, Andrew C Hayward, Malin Bergström, David Harrington, Charlotte Williams, Tanzina Haque, Dianne Irish, Adrienn Angyal, Marios Margaritis, Florencia Boshier, José Afonso Guerra-Assunção, Adela Alcolea-Medina, Angela Beckett, Themoula Charalampous, Raghavendran Kulasegaran Shylini, Beatrix Kele, Irene Monahan, Guy Mollett, Matthew Parker, Sunando Roy, Joshua Taylor, Sophie Weller, Eleri Wilson-Davies, Phillip Wade, Joseph Hughes, Tabitha Mahungu, Cassie Pope, Samuel Robson, Kordo Saeed, Thushan de Silva, Luke Snell, Adam A Witney, James Blackstone, Leanne Hockey, Georgia Marley, Christine Peters, Flavia Flaviani, Bindi Patel, Tom G S Williams, Rahul Batra, Jonathan D Edgeworth, Pinglawathee Madona, Jennifer Hart, Juanita Pang, Helena Tutill, Nadua Bayzid, Marius Cotic, Luke Green, Benjamin Lindsey, Amy State, Alison Cope, Peijun Zhang, Max Whiteley, Marta Gallis Ramalho, Stella Christou, Stavroula Louka, Hailey Hornsby, Benjamin Foulkes, Paige Wolverson, Joe Heffer, Nikki Smith, Salman Goudarzi, Chris Fearn, Kate Cook, Katie Loveson, Adhyana Mahamana, Buddhini Samaraweera, Siona Silveira, Stephen Aplin, Sarah Jeremiah, Matthew Harvey, Thea Sass, Ngee Keong Tan, Claudia Cardoso Pereira, Dan Frampton, Matt Byott, Judith Heaney, Emilie Sanchez, and Stavroula M Paraskevopoulou

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Published
2021
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11. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, and Peter Young

Subjects
Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Published
2021
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12. Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study [version 1; peer review: 2 approved]

Author

Michael Crone, Paul Randell, Zoey Herm, Arthi Anand, Saghar Missaghian-Cully, Loren Perelman, Panagiotis Pantelidis, and Paul Freemont

Subjects
Medicine, Science
Abstract

Background: Diagnostic laboratories are currently required to provide routine testing of asymptomatic staff and patients as a part of their clinical screening for SARS-CoV-2 infection. However, these cohorts display very different disease prevalence from symptomatic individuals and testing capacity for asymptomatic screening is often limited. Group testing is frequently proposed as a possible solution to address this; however, proposals neglect the technical and operational feasibility of implementation in a front-line diagnostic laboratory. Methods: Between October and December 2020, as a seven-week proof of concept, we took into account scientific, technical and operational feasibility to design and implement an adaptive pooling strategy in an NHS diagnostic laboratory in London (UK). We assessed the impact of pooling on analytical sensitivity and modelled the impact of prevalence on pooling strategy. We then considered the operational constraints to model the potential gains in capacity and the requirements for additional staff and infrastructure. Finally, we developed a LIMS-agnostic laboratory automation workflow and software solution and tested the technical feasibility of our adaptive pooling workflow. Results: First, we determined the analytical sensitivity of the implemented SARS-CoV-2 assay to be 250 copies/mL. We then determined that, in a setting with limited analyser capacity, the testing capacity could be increased by two-fold with pooling, however, in a setting with limited reagents, this could rise to a five-fold increase. These capacity increases could be realized with modest additional resource and staffing requirements whilst utilizing up to 76% fewer plastic consumables and 90% fewer reagents. Finally, we successfully implemented a plate-based pooling workflow and tested 920 patient samples using the reagents that would usually be required to process just 222 samples. Conclusions: Adaptive pooled testing is a scientifically, technically and operationally feasible solution to increase testing capacity in frontline NHS diagnostic laboratories.

Published
2021
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13. Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study

Author

Malick M Gibani, D Phil, Christofer Toumazou, ProfPhD, Mohammadreza Sohbati, PhD, Rashmita Sahoo, PhD, Maria Karvela, PhD, Tsz-Kin Hon, PhD, Sara De Mateo, PhD, Alison Burdett, PhD, K Y Felice Leung, PhD, Jake Barnett, MSc, Arman Orbeladze, MSc, Song Luan, PhD, Stavros Pournias, MSc, Jiayang Sun, MSc, Barney Flower, MRCP, Judith Bedzo-Nutakor, BSc, Maisarah Amran, MBBS, Rachael Quinlan, BSc, Keira Skolimowska, PhD, Carolina Herrera, PhD, Aileen Rowan, PhD, Anjna Badhan, PhD, Robert Klaber, MD, Gary Davies, MD, David Muir, FRCPath, Paul Randell, FRCPath, Derrick Crook, ProfFRCPath, Graham P Taylor, ProfDSc, Wendy Barclay, ProfPhD, Nabeela Mughal, FRCPath, Luke S P Moore, PhD, Katie Jeffery, PhD, and Graham S Cooke, ProfFRCP

Subjects
Medicine (General), R5-920, Microbiology, QR1-502
Abstract

Summary: Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86–98) with an overall specificity of 100% (99–100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85–98]; patients in the emergency department 100% [48–100]; and hospital inpatient admissions 100% [29–100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98–100]; patients in the emergency department 100% [69–100]; and hospital inpatient admissions 100% [96–100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20–31] in April, 2020) and low prevalence (3% [95% 1–9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA. Interpretation: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes. Funding: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.

Published
2020
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14. Development of a Multiplex Tandem PCR (MT-PCR) Assay for the Detection of Emerging SARS-CoV-2 Variants

Author

Richard Hale, Peter Crowley, Samir Dervisevic, Lindsay Coupland, Penelope R. Cliff, Saidat Ebie, Luke B. Snell, Joel Paul, Cheryl Williams, Paul Randell, Marcus Pond, and Keith Stanley

Subjects
SARS-CoV-2, variants, in vitro diagnostic test, Microbiology, QR1-502
Abstract

The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (

Published
2021
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16. Late-Onset Bloodstream Infection and Perturbed Maturation of the Gastrointestinal Microbiota in Premature Infants.

Author

Alexander G Shaw, Kathleen Sim, Paul Randell, Michael J Cox, Zoë E McClure, Ming-Shi Li, Hugo Donaldson, Paul R Langford, William O C M Cookson, Miriam F Moffatt, and J Simon Kroll

Subjects
Medicine, Science
Abstract

BACKGROUND:Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants. METHOD:Daily faecal samples and clinical data were collected over two years from 369 premature neonates (

Published
2015
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17. Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection

Author

Adam Stafford, Stephanie Rimmer, Mark Gilchrist, Kristi Sun, Ella P Davies, Claire S Waddington, Christopher Chiu, Darius Armstrong-James, Thomas Swaine, Frances Davies, Carlos H M Gómez, Vagish Kumar, Ahmad ElHaddad, Zaid Awad, Christopher Smart, Borja Mora-Peris, David Muir, Paul Randell, Joanna Peters, Meera Chand, Clare E Warrell, Tommy Rampling, Graham Cooke, Sara Dhanji, Vivienne Campbell, Carys Davies, Sana Osman, and Aula Abbara

Subjects
Infectious Diseases
Published
2023

18. Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study

Author

Douglas L Fink, Helen Callaby, Akish Luintel, William Beynon, Helena Bond, Eleanor Y Lim, Effrossyni Gkrania-Klotsas, Jospeh Heskin, Margherita Bracchi, Balram Rathish, Iain Milligan, Geraldine O'Hara, Stephanie Rimmer, Joanna R Peters, Lara Payne, Nisha Mody, Bethany Hodgson, Penny Lewthwaite, Rebecca Lester, Stephen D Woolley, Ann Sturdy, Ashley Whittington, Leann Johnson, Nathan Jacobs, John Quartey, Brendan AI Payne, Stewart Crowe, Ivo AM Elliott, Thomas Harrison, Joby Cole, Katie Beard, Tomas-Paul Cusack, Imogen Jones, Rishi Banerjee, Tommy Rampling, Jake Dunning, Iain D Milligan, Alison J Rodger, Sanjay R Bhagani, Lucy E Lamb, Rachel C Moores, Simon F K Lee, Colin S Brown, Susan Hopkins, Stephen Mepham, Simon Warren, Aoife Molloy, Ian Cropley, Alex Kew, Natasha Karunaharan, Antonia Scobie, Jennifer Hart, Dianne Irish, Tanzina Haque, Hamid Jalal, Robin Smith, Damien Mack, Tristan Barber, Fiona Burns, Robert Miller, Eleanor Hamlyn, Pedro Simoes, Breda Athan, Jennifer Abrahamsen, Jessica Joyce, Caroline Taylor, Sally Reddecliffe, Chloe Miller, Brooke Reeve, Hugh Kingston, Tim Crocker-Buque, Nicolas Massie, Ankush Dhariwal, Angelina Jayakumar, Robert Hammond, Alexandra Bramley, Tanmay Kanitkar, Laura Maynard-Smith, Eliza Gil, Cavan O'Connor, Derek Cocker, Wendy Spicer, Marisa Lanzman, Meera Thacker, Zoe O Anorson, Dharmesh Patel, Alan Williams, Catherine F Houlihan, Dominic Wakerley, Claire N Gordon, Daniel J Bailey, Jenna Furneaux, Abbie M Bown, Elizabeth J Truelove, Marian J Killip, David Jackson, Tracy L B Beetar-King, Ulrike M V Arnold, Rhea M Strachan, Jones Matthew, Hannah J Matthew, Jane C Osborne, Richard Vipond, Barry Gibney, Jodie Owen, Will Beynon, Michael Hunter, Louise McCorry, Carol Emerson, Say Quah, Suzanne Todd, Emma McCarty, Eoin Walker, Susan Feeney, Tanya Curran, Kathy Li, JD Mullan, Kate Jackson, Peter Nelson, Kevin Lewis, Mark McNicol, Marcus Pratt, Anna Smith, Erin Vos, Fahad Alsalemee, Daniel O Leary, John Canny, Katherine McGinnity, Carly Culbert, Conor McDowell, Cathy McQuillan, Eunjin Jeong, Lynsey Glass, Jessica Dyche, Paula McClean, Rebecca Stewart, Harold Ursolino, Melissa Perry, Hannah McCormick, Joseph Heskin, Nicklas Brown, Thomas Juniper, Borja Mora-Peris, Alessia Dalla-Pria, Nicola Mackie, Lucy Garvey, Alan Winston, Graham Cooke, Mark Nelson, Emer Kilbride, Ala Elbishi, William Kerrigan, Joshua Silva, Jesal Gohil, Sasha Payagala, Yasmin Walters, Joanna Smith, Jonathan Goodfellow, Kitty Lyons, Hsiu Tung, Kinjal Patel, Merle Henderson, Michael Butler, Edu Peres, Taiana Silva Carvalho, Antoine Joly, Molly Dickinson, Luke S P Moore, Nabeela Mughal, Stephen Hughes, Shrada Chitlangia, Priyanka Viramgana, Ruth Byrne, Paul Randell, Luigi Strangis, Nicola Poveda, Deborah Bovey, Poppy Richardson, Vivian Heaslip, Christopher Higgs, Marta Boffito, Nicolo Girometti, Gary Whitlock, Victoria Tittle, Rachel Jones, Michael Rayment, Christopher Scott, David Asboe, Marcus Pond, David Muir, Movin Abeywickrema, Sarah-Lou Bailey, Sara E Boyd, Dayana Da Silva Fontoura, Anna Daunt, Claire Y Mason, Jamie Murphy, Vasanth V Naidu, Aatish Patel, Caitlin Pley, Ethan Redmore, Katherine Sharrocks, Luke B Snell, Rohan Sundramoorthi, Jerry C H Tam, Aisling Brown, Sam Douthwaite, Anna Goodman, Gaia Nebbia, William Newsholme, Nicholas Price, Emily Shaw, Alex Salam, Claire van Nispen tot Pannerden, Helen Winslow, Julia Bilinska, Sarah Keegan, Harry Coleman, Jessica Doctor, Nasreen Moini, Daniella Chilton, Golaleh Haidari, Rebecca Simons, Rajababu Kulasegaram, Nick Larbalestier, Achyuta Nori, Jack R Potter, Cecilia Tuudah, Paul Wade, Alexandra Travers, Sarah Dunford, Joshua Greenwood, Georgina Oledimmah, Lesley Gyampo, Pedro SA Pinto, AbdulKadir Muse, Zoe Parker, Charlotte Alexander, Alexander Khan, Medinat Ajayi, Abigail Baltazar, Davis Sharella, Nasra Hersi, Thuy Nguyen, Rugiatu Timbo, Ismail Jalloh, Susan Bryan, Patricia Clarke, Marcia Kerr, Fidelis Amedu, Maria BohoBonaba, Sarah Haque, Michelle Howson, Norbai Tambilawan, Soledad Yupanqui Estay, Hawanatu Bangura, Tseday Gideon, Damilola Jerome-oboh, Linda Tetteh, Chioma Nwagu, Viwoalo Agbaglah, Nona Narag, Mahima Zaveri, Maedhbh Ni Luanaigh, Peggy Keane, Aula Abbara, Olamide Dosekun, Mhairi Bolland, Adam Stafford, Dina Saleh, Rhianna Sheridan, Ella Davies, Kristi Sun, Mark Gilchrist, Priti Kukadia, Muhammed Embrahimsa, Christopher Chiu, Lauren Taylor, Charlotte Short, Jasmini Alagratnam, Iresh Jayaweera, Kavitha Gundugola, Lara V S Payne, Killian Quinn, Caoimhe Nic Fhogartaigh, Nivenjit Kaur, Salmaan Bholah, Kajann Kantha, Jonathan Youngs, Temi Lampejo, Nicholas Pitto, David S Lawrence, Holly Middleditch, Lourdes Dominguez-Dominguez, Ayoma Ratnappuli, Sara Al-Hashimi, Amelia Oliveira, Zoe Ottaway, Larissa Mulka, Anne M Neary, Michael R Downey, Danielle C Lucy, Craig I McCallum, Michael Beadsworth, Libuse Ratcliffe, Tom E Fletcher, Gerry Davies, Nicholas Wong, Stephen Aston, Thomas E Wingfield, Thomas Blanchard, Paul Hine, Susie Gould, Christopher Smith, Michael Abouyannis, Abolaji Atomode, James Cruise, Merna Samual, Nicola Scott, Vino Srirathan, Joseph Lewis, Lauren Richards, Mary-Ann Cummings, Emily Gillan, Rebecca Peers, Amy Tickle, Grace Keating, Tendi Chinyanda, Mav Sanchez, Daniel Harrison, null Hoyle, Ben Metcalfe, Jennifer Taylor, Nicky Johnson, Neil Kelle, Kirsty McDowell, Ian Richardson, Monette Saguidan, Nicky Farmer, Angella Gillespie, Shay Willoughby, Samantha Parker, Shamseena Avulan, Shazia Arif, Suzanne Marshall, David Carlisle, Mohsen Rezaei, Angela Booth, Joanne Watts, Lauren Tremarco, Priyanga Jeyanayagam, Odinaka Ubochi, Daniel Vagianos, Mark Richardson, Anthony Jarvis, Kyra Gow, Jade Walmsley, Adam O'keefe, Anna Smielewska, Mark Hopkins, Fatima Balane, Sarah Bradley, Tumena Corrah, Venus Daquiz, Christopher Dugan, Joshua Elliot, Fiona Foley, Dawn Friday, May Gamit, David Garner, Karishma Gokani, Laurence John, Deepa Joseph, Nuzhath Khan, Cherifer Mamuyac, Alastair McGregor, John McSorley, Victoria Parris, Luciana Rubinstein, Julian Rycroft, Kelcy Salinas, Jason Salinas, Jency Sebatian, Melanie Smith, Marina Tejero Garcia, Uchenna Ume, Margarete Vicentine, Gabriel Wallis, Alec Bonington, Alison Uriel, Andrew Ustianowski, Balazs Dancso, Celia Hogan, Clare van Halsema, F Javier Vilar, Karen Devine, Katherine Ajdukiewicz, Rajesh Rajendran, Samit Ghosh, Michael Riste, Nicholas Machin, Chitra Babu, Shazaad Ahmad, Dorcas Obeng, Farnaz Dave, Gavin Conolley, Joseph Thompson, Maya Tickell-Painter, Prasun Chakravorty, Rachel Pringle, Mohammad R Zafar, Sarah Lawrence, Amada Sanchez-Gonzalez, Cristina Fernandez, Lynsey Goodwin, David Carey, Molly Howarth-Maddison, Samuel Moody, Rebecca Upton, Christina Apthorp, Charlotte Murray, Kirstie Salthouse, Sabah Nadeem, Grant Ridley, Francesca White, Andrew Brown, Michael Lawless, Mohamed Mohamed, Robert Mulligan, Amy Belfield, Jacob Brolly, Maria Calderon, James Cheveau, Milo Cullinan, Sophie Garrad, Will Griffiths, Aidan Ireland, Peter Ireland, Charlotte Milne, Paul Nwajiugo, Bijan Ghavami-Kia, Chris Duncan, Adam Evans, Ewan Hunter, Ashley Price, Matthias Schmid, Uli Schwab, Yusri Taha, Brendan Payne, Ivo A M Elliott, Charles J Woodrow, Drosos E Karageorgopoulos, Peter J Davis, Emily Lord, Oliver J Bannister, Andrew B Dagens, Anne Tunbridge, Saher Choudry, Adam Telfer, Ihsan Jhibril, Syed N Atta, Ben Stone, Cariad Evans, Mike Ankcorn, Suha Akili, Mehmet Yavuz, Vicky Goodall, Sam Farrow, Georgina Mountford, Kate Beard, Julian Sutton, Tristan Clark, Annette Mason, Mike Vickers, Derek Macallan, Tihana Bicanic, Angela Houston, Cassie Pope, NgeeKeong Tan, Christopher Ward, Jonathan Cohen, Marieke Emonts-le Clercq, David Porter, Andrew Riordan, Ruchi Sinha, Elizabeth Whittaker, and Monkeypox, Specialist and High Consequence Infectious Diseases Centres Network for

Subjects
Infectious Diseases
Abstract

Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Published
2023

19. Tale of two viruses: parvovirus B19 and HIV

Author

Caroline Foster, Paul Randell, Sarah Fidler, and Hayley Hernstadt

Subjects
Pediatrics, medicine.medical_specialty, viruses, medicine.medical_treatment, Hydrops Fetalis, Human immunodeficiency virus (HIV), Erythema Infectiosum, Context (language use), Case Report, medicine.disease_cause, Parvoviridae Infections, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Pregnancy, hemic and lymphatic diseases, medicine, Parvovirus B19, Human, Humans, 030212 general & internal medicine, Pregnancy Complications, Infectious, 030219 obstetrics & reproductive medicine, biology, Parvovirus, business.industry, Parvovirus infection, virus diseases, Immunosuppression, General Medicine, biology.organism_classification, medicine.disease, Female, business, Severe anaemia
Abstract

We present a HIV-infected patient who developed severe anaemia due to chronic parvovirus B19 infection and subsequently had an unplanned pregnancy. This is in the context of poor adherence to antiretroviral therapy and significant immunosuppression; there was a delay in diagnosis of chronic parvovirus infection due to attribution of anaemia to HIV. She received immunoglobulin therapy and effective antiretroviral therapy, with reduction in parvovirus load and improvement in anaemia. She was counselled regarding the need for monitoring in pregnancy due to risk of intrauterine infection. We review the literature of management of chronic parvovirus infection in the immunosuppressed and the consequences of intrauterine infection.

Published
2023

20. Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Author

S. Cotton, M.P. McHugh, R. Dewar, J.G. Haas, K. Templeton, Samuel C. Robson, Thomas R. Connor, Nicholas J. Loman, Tanya Golubchik, Rocio T. Martinez Nunez, David Bonsall, Andrew Rambaut, Luke B. Snell, Rich Livett, Catherine Ludden, Sally Corden, Eleni Nastouli, Gaia Nebbia, Ian Johnston, Jacqui A. Prieto, Kordo Saeed, David K. Jackson, Catherine Houlihan, Dan Frampton, William L. Hamilton, Adam A. Witney, Giselda Bucca, Cassie F. Pope, Catherine Moore, Emma C. Thomson, Teresa Cutino-Moguel, Ewan M. Harrison, Colin P. Smith, Fiona Rogan, Shaun M. Beckwith, Abigail Murray, Dawn Singleton, Kirstine Eastick, Liz A. Sheridan, Paul Randell, Leigh M. Jackson, Cristina V. Ariani, Sónia Gonçalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Samuel Moses, Sam Nicholls, Matthew Bull, Roberto Amato, Darren L. Smith, David M. Aanensen, Jeffrey C. Barrett, Beatrix Kele, Dinesh Aggarwal, James G. Shepherd, Martin D. Curran, Surendra Parmar, Matthew D. Parker, Catryn Williams, Sharon Glaysher, Anthony P. Underwood, Matthew Bashton, Nicole Pacchiarini, Katie F. Loveson, Matthew Byott, Alessandro M. Carabelli, Kate E. Templeton, Sharon J. Peacock, Thushan I. de Silva, Dennis Wang, Cordelia F. Langford, John Sillitoe, Rory N. Gunson, Simon Cottrell, Justin O’Grady, Dominic Kwiatkowski, Patrick J. Lillie, Nicholas Cortes, Nathan Moore, Claire Thomas, Phillipa J. Burns, Tabitha W. Mahungu, Steven Liggett, Angela H. Beckett, Matthew TG. Holden, Lisa J. Levett, Husam Osman, Mohammed O. Hassan-Ibrahim, David A. Simpson, Meera Chand, Ravi K. Gupta, Alistair C. Darby, Steve Paterson, Oliver G. Pybus, Erik M. Volz, Daniela de Angelis, David L. Robertson, Andrew J. Page, Inigo Martincorena, Louise Aigrain, Andrew R. Bassett, Nick Wong, Yusri Taha, Michelle J. Erkiert, Michael H. Spencer Chapman, Rebecca Dewar, Martin P. McHugh, Siddharth Mookerjee, Stephen Aplin, Matthew Harvey, Thea Sass, Helen Umpleby, Helen Wheeler, James P. McKenna, Ben Warne, Joshua F. Taylor, Yasmin Chaudhry, Rhys Izuagbe, Aminu S. Jahun, Gregory R. Young, Claire McMurray, Clare M. McCann, Andrew Nelson, Scott Elliott, Hannah Lowe, Anna Price, Matthew R. Crown, Sara Rey, Sunando Roy, Ben Temperton, Sharif Shaaban, Andrew R. Hesketh, Kenneth G. Laing, Irene M. Monahan, Judith Heaney, Emanuela Pelosi, Siona Silviera, Eleri Wilson-Davies, Helen Fryer, Helen Adams, Louis du Plessis, Rob Johnson, William T. Harvey, Joseph Hughes, Richard J. Orton, Lewis G. Spurgin, Yann Bourgeois, Chris Ruis, Áine O'Toole, Marina Gourtovaia, Theo Sanderson, Christophe Fraser, Jonathan Edgeworth, Judith Breuer, Stephen L. Michell, John A. Todd, Michaela John, David Buck, Kavitha Gajee, Gemma L. Kay, David Heyburn, Themoula Charalampous, Adela Alcolea-Medina, Katie Kitchman, Alan McNal, David T. Pritch, Samir Dervisevic, Peter Muir, Esther Robinson, Barry B. Vipond, Newara A. Ramadan, Christopher Jeanes, Danni Weldon, Jana Catalan, Neil Jones, Ana da Silva Filipe, Chris Williams, Marc Fuchs, Julia Miskelly, Aaron R. Jeffries, Karen Oliver, Naomi R. Park, Amy Ash, Cherian Koshy, Magdalena Barrow, Sarah L. Buchan, Anna Mantzouratou, Gemma Clark, Christopher W. Holmes, Sharon Campbell, Thomas Davis, Ngee Keong Tan, Julianne R. Brown, Kathryn A. Harris, Stephen P. Kidd, Paul R. Grant, Li Xu-McCrae, Alison Cox, Pinglawathee Madona, Marcus Pond, Paul A. Randell, Karen T. Withell, Cheryl Williams, Clive Graham, Rebecca Denton-Smith, Emma Swindells, Robyn Turnbull, Tim J. Sloan, Andrew Bosworth, Stephanie Hutchings, Hannah M. Pymont, Anna Casey, Liz Ratcliffe, Christopher R. Jones, Bridget A. Knight, Tanzina Haque, Jennifer Hart, Dianne Irish-Tavares, Eric Witele, Craig Mower, Louisa K. Watson DipHE, Jennifer Collins, Gary Eltringham, Dorian Crudgington, Ben Macklin, Miren Iturriza-Gomara, Anita O. Lucaci, Patrick C. McClure, Matthew Carlile, Nadine Holmes, Christopher Moore, Nathaniel Storey, Stefan Rooke, Gonzalo Yebra, Noel Craine, Malorie Perry, Nabil-Fareed Alikhan, Stephen Bridgett, Kate F. Cook, Christopher Fearn, Salman Goudarzi, Ronan A. Lyons, Thomas Williams, Sam T. Haldenby, Jillian Durham, Steven Leonard, Robert M. Davies, Rahul Batra, Beth Blane, Moira J. Spyer, Perminder Smith, Mehmet Yavus, Rachel J. Williams, Adhyana IK. Mahanama, Buddhini Samaraweera, Sophia T. Girgis, Samantha E. Hansford, Angie Green, Charlotte Beaver, Katherine L. Bellis, Matthew J. Dorman, Sally Kay, Liam Prestwood, Shavanthi Rajatileka, Joshua Quick, Radoslaw Poplawski, Nicola Reynolds, Andrew Mack, Arthur Morriss, Thomas Whalley, Bindi Patel, Iliana Georgana, Myra Hosmillo, Malte L. Pinckert, Joanne Stockton, John H. Henderson, Amy Hollis, William Stanley, Wen C. Yew, Richard Myers, Alicia Thornton, Alexander Adams, Tara Annett, Hibo Asad, Alec Birchley, Jason Coombes, Johnathan M. Evans, Laia Fina, Bree Gatica-Wilcox, Lauren Gilbert, Lee Graham, Jessica Hey, Ember Hilvers, Sophie Jones, Hannah Jones, Sara Kumziene-Summerhayes, Caoimhe McKerr, Jessica Powell, Georgia Pugh, Sarah Taylor, Alexander J. Trotter, Charlotte A. Williams, Leanne M. Kermack, Benjamin H. Foulkes, Marta Gallis, Hailey R. Hornsby, Stavroula F. Louka, Manoj Pohare, Paige Wolverson, Peijun Zhang, George MacIntyre-Cockett, Amy Trebes, Robin J. Moll, Lynne Ferguson, Emily J. Goldstein, Alasdair Maclean, Rachael Tomb, Igor Starinskij, Laura Thomson, Joel Southgate, Moritz UG. Kraemer, Jayna Raghwani, Alex E. Zarebski, Olivia Boyd, Lily Geidelberg, Chris J. Illingworth, Chris Jackson, David Pascall, Sreenu Vattipally, Timothy M. Freeman, Sharon N. Hsu, Benjamin B. Lindsey, Keith James, Kevin Lewis, Gerry Tonkin-Hill, Jaime M. Tovar-Corona, MacGregor Cox, Khalil Abudahab, Mirko Menegazzo, Ben EW. Taylor, Corin A. Yeats, Afrida Mukaddas, Derek W. Wright, Leonardo de Oliveira Martins, Rachel Colquhoun, Verity Hill, Ben Jackson, J.T. McCrone, Nathan Medd, Emily Scher, Jon-Paul Keatley, Tanya Curran, Sian Morgan, Patrick Maxwell, Ken Smith, Sahar Eldirdiri, Anita Kenyon, Alison H. Holmes, James R. Price, Tim Wyatt, Alison E. Mather, Timofey Skvortsov, John A. Hartley, Martyn Guest, Christine Kitchen, Ian Merrick, Robert Munn, Beatrice Bertolusso, Jessica Lynch, Gabrielle Vernet, Stuart Kirk, Elizabeth Wastnedge, Rachael Stanley, Giles Idle, Declan T. Bradley, Nicholas F. Killough, Jennifer Poyner, Matilde Mori, Owen Jones, Victoria Wright, Ellena Brooks, Carol M. Churcher, Laia Delgado Callico, Mireille Fragakis, Katerina Galai, Andrew Jermy, Sarah Judges, Anna Markov, Georgina M. McManus, Kim S. Smith, Peter MD. Thomas-McEwen, Elaine Westwick, Stephen W. Attwood, Frances Bolt, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Lizzie Meadows, Sarah Jeremiah, Nikki Smith, Luke Foulser, Amita Patel, Louise Berry, Tim Boswell, Vicki M. Fleming, Hannah C. Howson-Wells, Amelia Joseph, Manjinder Khakh, Michelle M. Lister, Paul W. Bird, Karlie Fallon, Thomas Helmer, Claire L. McMurray, Mina Odedra, Jessica Shaw, Julian W. Tang, Nicholas J. Willford, Victoria Blakey, Veena Raviprakash, Nicola Sheriff, Lesley-Anne Williams, Theresa Feltwell, Luke Bedford, James S. Cargill, Warwick Hughes, Jonathan Moore, Susanne Stonehouse, Laura Atkinson, Jack CD. Lee, Divya Shah, Natasha Ohemeng-Kumi, John Ramble, Jasveen Sehmi, Rebecca Williams, Wendy Chatterton, Monika Pusok, William Everson, Anibolina Castigador, Emily Macnaughton, Kate El Bouzidi, Temi Lampejo, Malur Sudhanva, Cassie Breen, Graciela Sluga, Shazaad SY. Ahmad, Ryan P. George, Nicholas W. Machin, Debbie Binns, Victoria James, Rachel Blacow, Lindsay Coupland, Louise Smith, Edward Barton, Debra Padgett, Garren Scott, Aidan Cross, Mariyam Mirfenderesky, Jane Greenaway, Kevin Cole, Phillip Clarke, Nichola Duckworth, Sarah Walsh, Kelly Bicknell, Robert Impey, Sarah Wyllie, Richard Hopes, Chloe Bishop, Vicki Chalker, Ian Harrison, Laura Gifford, Zoltan Molnar, Cressida Auckland, Cariad Evans, Kate Johnson, David G. Partridge, Mohammad Raza, Paul Baker, Stephen Bonner, Sarah Essex, Leanne J. Murray, Andrew I. Lawton, Shirelle Burton-Fanning, Brendan AI. Payne, Sheila Waugh, Andrea N. Gomes, Maimuna Kimuli, Darren R. Murray, Paula Ashfield, Donald Dobie, Fiona Ashford, Angus Best, Liam Crawford, Nicola Cumley, Megan Mayhew, Oliver Megram, Jeremy Mirza, Emma Moles-Garcia, Benita Percival, Megan Driscoll, Leah Ensell, Helen L. Lowe, Laurentiu Maftei, Matteo Mondani, Nicola J. Chaloner, Benjamin J. Cogger, Lisa J. Easton, Hannah Huckson, Jonathan Lewis, Sarah Lowdon, Cassandra S. Malone, Florence Munemo, Manasa Mutingwende, Roberto Nicodemi, Olga Podplomyk FD, Thomas Somassa, Andrew Beggs, Alex Richter, Claire Cormie, Joana Dias, Sally Forrest, Ellen E. Higginson, Mailis Maes, Jamie Young, Rose K. Davidson, Kathryn A. Jackson, Alexander J. Keeley, Jonathan Ball, Timothy Byaruhanga, Joseph G. Chappell, Jayasree Dey, Jack D. Hill, Emily J. Park, Arezou Fanaie, Rachel A. Hilson, Geraldine Yaze, Stephanie Lo, Safiah Afifi, Robert Beer, Joshua Maksimovic, Kathryn McCluggage, Karla Spellman, Catherine Bresner, William Fuller, Angela Marchbank, Trudy Workma, Ekaterina Shelest, Johnny Debebe, Fei Sang, Sarah Francois, Bernardo Gutierrez, Tetyana I. Vasylyeva, Flavia Flaviani, Manon Ragonnet-Cronin, Katherine L. Smollett, Alice Broos, Daniel Mair, Jenna Nichols, Kyriaki Nomikou, Lily Tong, Ioulia Tsatsani, Sarah O'Brien, Steven Rushton, Roy Sanderson, Jon Perkins, Seb Cotton, Abbie Gallagher, Elias Allara, Clare Pearson, David Bibby, Gavin Dabrer, Nicholas Ellaby, Eileen Gallagher, Jonathan Hubb, Angie Lackenby, David Lee, Nikos Manesis, Tamyo Mbisa, Steven Platt, Katherine A. Twohig, Mari Morgan, Alp Aydin, David J. Baker, Ebenezer Foster-Nyarko, Sophie J. Prosolek, Steven Rudder, Chris Baxter, Sílvia F. Carvalho, Deborah Lavin, Arun Mariappan, Clara Radulescu, Aditi Singh, Miao Tang, Helen Morcrette, Nadua Bayzid, Marius Cotic, Carlos E. Balcazar, Michael D. Gallagher, Daniel Maloney, Thomas D. Stanton, Kathleen A. Williamson, Robin Manley, Michelle L. Michelsen, Christine M. Sambles, David J. Studholme, Joanna Warwick-Dugdale, Richard Eccles, Matthew Gemmell, Richard Gregory, Margaret Hughes, Charlotte Nelson, Lucille Rainbow, Edith E. Vamos, Hermione J. Webster, Mark Whitehead, Claudia Wierzbicki, Adrienn Angyal, Luke R. Green, Max Whiteley, Emma Betteridge, Iraad F. Bronner, Ben W. Farr, Scott Goodwin, Stefanie V. Lensing, Shane A. McCarthy, Michael A. Quail, Diana Rajan, Nicholas M. Redshaw, Carol Scott, Lesley Shirley, Scott AJ. Thurston, Will Rowe, Amy Gaskin, Thanh Le-Viet, James Bonfield, Jennifier Liddle, Andrew Whitwham, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, and Apollo - University of Cambridge Repository

Subjects
Microbiology (medical), MCC, Introduction, SARS-CoV-2, NDAS, COVID-19, Care homes, General Medicine, NIS, Patient Discharge, Hospitals, Hospitalization, Infectious Diseases, SDG 3 - Good Health and Well-being, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Hospital discharge
Abstract

COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF

Published
2023

21. Characterization of Rare Spontaneous Human Immunodeficiency Virus Viral Controllers Attending a National United Kingdom Clinical Service Using a Combination of Serology and Molecular Diagnostic Assays

Author

Maryam Khan, Daniel Bradshaw, Colin S Brown, Jana Haddow, Poorvi Patel, Jennifer H C Tosswill, Katrina Pollock, Tamara Elliott, Xinzhu Wang, Jasmini Alagaratnam, Borja Mora-Peris, Steve Kaye, Myra O McClure, David Muir, Paul Randell, Graham P Taylor, and Sarah J Fidler

Subjects
Infectious Diseases, Oncology
Abstract

Background We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805–1336), and normal CD4/CD8 ratio (median 1.8, range 1.2–1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4–14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

Published
2023

22. Real-world evaluation of COVID-19 lateral flow device (LFD) mass-testing in healthcare workers at a London hospital; a prospective cohort analysis

Author

Michael Rayment, Nabeela Mughal, Paul Randell, Rachael Jones, Georgia Lamb, Gary W Davies, Joseph Heskin, and Luke Sp Moore

Subjects
Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Health Personnel, Lateral flow assay, Microbiology, Asymptomatic, Cohort Studies, COVID-19 Testing, Internal medicine, London, Health care, False positive paradox, medicine, Lateral flow tests, Humans, Prospective Studies, Prospective cohort study, Letter to the Editor, Diagnostics, High prevalence, SARS-CoV-2, business.industry, COVID-19, food and beverages, 1103 Clinical Sciences, Inova, Hospitals, Infectious Diseases, Point-of-care, medicine.symptom, business, Cohort study, Lateral flow immunoassay
Abstract

Objectives Real-world evaluation of the performance of the Innova lateral flow immunoassay antigen device (LFD) for regular COVID-19 testing of hospital workers. Methods This prospective cohort analysis took place at a London NHS Trust. 5076 secondary care healthcare staff participated in LFD testing from 18 November 2020 to21 January 2021. Staff members submitted results and symptoms via an online portal twice weekly. Individuals with positive LFD results were invited for confirmatory SARS CoV-2 PCR testing. The positive predictive value (PPV) of the LFD was measured. Secondary outcome measures included time from LFD result to PCR test and staff symptom profiles. Results 284/5076 individuals reported a valid positive LFD result, and a paired PCR result was obtained in 259/284 (91.2%). 244 were PCR positive yielding a PPV of 94.21% (244/259, 95% CI 90.73% to 96.43%). 204/259 (78.8%) staff members had the PCR within 36 hours of the LFD test. Symptom profiles were confirmed for 132/244 staff members (54.1%) with positive PCR results (true positives) and 13/15 (86.6%) with negative PCR results (false positives). 91/132 true positives (68.9%) were symptomatic at the time of LFD testing: 65/91 (71.4%) had symptoms meeting the PHE case definition of COVID-19, whilst 26/91 (28.6%) had atypical symptoms. 18/41 (43.9%) staff members who were asymptomatic at the time of positive LFD developed symptoms in the subsequent four days. 9/13 (76.9%) false positives were asymptomatic, 1/13 (7.7%) had atypical symptoms and 3/13 (23.1%) had symptoms matching the PHE case definition. Conclusions The PPV of the Innova LFD is high when used amongst hospital staff during periods of high prevalence of COVID-19, yet we find frequent use by symptomatic staff rather than as a purely asymptomatic screening tool. LFD testing does allow earlier isolation of infected workers and facilitates detection of individuals whose symptoms do not qualify for PCR testing.

Published
2021

23. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression

Author

Maria Prendecki, Sarah A. Gleeson, Aran Singanayagam, Paige M Mortimer, Helena Edwards, Anand Shah, Paul Randell, Tina Thomson, Stephen P. McAdoo, Paul Martin, Michelle Willicombe, Stacey McIntyre, Alison Cox, Liz Lightstone, Candice Clarke, and Peter Kelleher

Subjects
Adult, Male, COVID-19 Vaccines, T-Lymphocytes, medicine.medical_treatment, Immunology, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, 1117 Public Health and Health Services, Autoimmune Diseases, Serology, Immunocompromised Host, Immunogenicity, Vaccine, rituximab, Immune system, Rheumatology, B-lymphocytes, Humans, Immunology and Allergy, Medicine, Seroconversion, Aged, Immunity, Cellular, biology, SARS-CoV-2, business.industry, Immunogenicity, ELISPOT, COVID-19, 1103 Clinical Sciences, Immunosuppression, Middle Aged, vaccination, Antibodies, Neutralizing, Arthritis & Rheumatology, Immunity, Humoral, Treatment, Vaccination, 1107 Immunology, biology.protein, Female, Antibody, business, Immunosuppressive Agents
Abstract

ObjectiveThere is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.MethodsSerological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.ResultsFollowing first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

Published
2021

24. Prior COVID-19 protects against reinfection, even in the absence of detectable antibodies

Author

John Samuel Busby, Maximillian Shahin Habibi, Kate El Bouzidi, T. Planche, Peter Riley, Aodhan Breathnach, William Peter Kelleher, Scott John Charles Pallett, Brendan Alexander Ingelby Payne, Paul Randell, Malur Sudhanva, Christopher J A Duncan, and Aidan T Hanrath

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Infectious Diseases, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), biology.protein, Medicine, Antibody, business, Virology
Published
2021

25. Early identification of high-risk individuals for monoclonal antibody therapy and prophylaxis is feasible by SARS-CoV-2 anti-spike antibody specific lateral flow assay

Author

Scott J.C. Pallett, Michael Rayment, Joseph Heskin, Andrea Mazzella, Rachael Jones, Nabeela Mughal, Paul Randell, Gary W. Davies, and Luke S.P. Moore

Subjects
Microbiology (medical), Monoclonal antibody, Adult, Male, SARS-CoV-2, COVID-19, Antibodies, Monoclonal, 1103 Clinical Sciences, General Medicine, Lateral flow assay, Antibodies, Viral, Microbiology, COVID-19 Drug Treatment, Infectious Diseases, Immunoglobulin M, 1108 Medical Microbiology, Immunoglobulin G, Humans, Female, 0605 Microbiology
Abstract

Monoclonal antibody therapy has been approved for prophylaxis and treatment of severe COVID-19 infection. Greatest benefit appears limited to those yet to mount an effective immune response from natural infection or vaccination, but concern exists around ability to make timely assessment of immune status of community-based patients where laboratory-based serodiagnostics predominate. Participants were invited to undergo paired laboratory-based (Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle immunoassay) and lateral flow assays (LFA; a split SARS-CoV-2 IgM/IgG and total antibody test) able to detect SARS-CoV-2 anti-spike antibodies. LFA band strength was compared with CMIA titer by log-linear regression. Two hundred individuals (median age 43.5 years, IQR 30-59; 60.5% female) underwent testing, with a further 100 control sera tested. Both LFA band strengths correlated strongly with CMIA antibody titers (P < 0.001). LFAs have the potential to assist in early identification of seronegative patients who may demonstrate the greatest benefit from monoclonal antibody treatment.

Published
2022

26. Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection

Author

Maria Prendecki, Eleanor Parker, Graham Pickard, Louise Greathead, Megan Griffith, Richard S. Tedder, Myra O. McClure, Alison J. Cox, Claire Edwards, Paul Randell, Liz Lightstone, Virginia Prout, Michelle Willicombe, Stephen P. McAdoo, Amrita Dhutia, Rawya Charif, Federica Marchesin, Jaslyn Gan, Candice Clarke, Mary Guckian, Peter Kelleher, and Imperial Health Charity

Subjects
Male, 0301 basic medicine, Cellular immunity, medicine.medical_specialty, T cell, medicine.medical_treatment, 030232 urology & nephrology, serology, Antibodies, Viral, Polymerase Chain Reaction, Gastroenterology, Asymptomatic, Serology, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Immune system, Renal Dialysis, Immunity, Internal medicine, Humans, Medicine, Serologic Tests, Clinical Investigation, Pandemics, hemodialysis, biology, SARS-CoV-2, business.industry, COVID-19, 1103 Clinical Sciences, Urology & Nephrology, Haemodialysis, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Reinfection, biology.protein, Kidney Failure, Chronic, Female, Hemodialysis, medicine.symptom, Antibody, business
Abstract

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity., Graphical abstract

Published
2021

27. Third primary SARS-CoV-2 prophylactic mRNA vaccines enhances antibody responses in the majority of patients with haematological malignancies: Results from the MARCH study

Author

Lucy Cook, Gillian O'Dell, Eleni Vourvou, Renuka Palanicawandar, Sasha Marks, Dragana Milojkovic, Jane Apperley, Sandra Loaiza, Simone Claudiani, Marco Bua, Catherine Hockings, Donald MacDonald, Aristeidis Chaidos, Jiri Pavlu, Nichola Cooper, Sarah Fidler, Paul Randell, and Andrew Innes

Abstract

SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have successfully reduced hospitalisations and deaths, but the efficacy of vaccination in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. Here we quantify serological responses following these vaccines in a cohort of 381 patients with haematological malignancies attending routine haematology outpatient clinics. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued sub-optimal vaccine responses who may benefit from additional doses, as well as early intervention with monoclonal therapies in the event of developing SARS-CoV-2 infection.

Published
2022

29. Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine

Author

Alessia Dalla Pria, Maria Prendecki, Stephen P. McAdoo, Candice Clarke, Xiao-Ning Xu, Jonathan Brown, Alison Cox, Liz Lightstone, Mary Guckian, Paul Randell, Michelle Willicombe, Wendy S. Barclay, Sarah Gleeson, and Peter Kelleher

Subjects
Adult, Enzyme-Linked Immunospot Assay, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), T-Lymphocytes, T cell, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunity, General & Internal Medicine, Correspondence, medicine, Humans, 11 Medical and Health Sciences, BNT162 Vaccine, Aged, SARS-CoV-2, business.industry, ELISPOT, COVID-19, General Medicine, Middle Aged, Virology, Immunity, Humoral, medicine.anatomical_structure, Spike Glycoprotein, Coronavirus, Enzyme linked immunospot assay, business
Published
2021

31. High rates of SARS-CoV-2 seropositivity in nursing home residents

Author

Cornelia Junghans, Frances Sanderson, David J. Sharp, Shamez N Ladhani, Graham Nsn, Nicola Lang, Paul Randell, Robert McLaren, and UK DRI Ltd

Subjects
Microbiology (medical), High rate, Infection Control, 2019-20 coronavirus outbreak, medicine.medical_specialty, Science & Technology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, 1103 Clinical Sciences, Microbiology, Article, Nursing Homes, Infectious Diseases, Seroepidemiologic Studies, Emergency medicine, medicine, Humans, Nursing homes, business, Life Sciences & Biomedicine
Published
2021

32. Handheld Point-of-Care System for Rapid Detection of SARS-CoV-2 Extracted RNA in under 20 min

Author

Wendy S. Barclay, Frances Bolt, Jesus Rodriguez-Manzano, Kenny Malpartida-Cardenas, Alison Holmes, Luca Miglietta, Matthew L. Cavuto, Pantelis Georgiou, Giovanni Satta, Rebecca Penn, Nicolas Moser, Paul Randell, Ivana Pennisi, Frances Davies, Ahmad Moniri, Imperial College COVID-19 Research Fund, and National Institute for Health Research

Subjects
High rate, Detection limit, Chromatography, Coronavirus disease 2019 (COVID-19), 010405 organic chemistry, business.industry, General Chemical Engineering, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Loop-mediated isothermal amplification, RNA, General Chemistry, 010402 general chemistry, 01 natural sciences, Rapid detection, 0104 chemical sciences, Chemistry, Medicine, 03 Chemical Sciences, business, QD1-999, Research Article, Point of care
Abstract

The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (, A CMOS-based point-of-care diagnostic platform for isothermal amplification/detection of SARS-CoV-2 RNA within 20 min coupled to a smartphone for data visualization and geolocalization is presented.

Published
2021

33. British HIV Association/British Association for Sexual Health and HIV/British Infection Association adult HIV testing guidelines 2020

Author

Daniel Clutterbuck, Alan White, Kat Smithson, Ann Sullivan, Philippa C Matthews, Tim E. A. Peto, Gillian Dean, Martin Murchie, Chamut Kifetew, Valerie Delpech, A. G. Buckley, J. Josh, Fiona Burns, Nicola Mackie, Emma Young, Adrian Palfreeman, Ian Cormack, Hannah Skene, Laura Waters, Roy Trevelion, Michael Rayment, Anthony Nardone, Nick Larbalestier, Sara Croxford, Karen Trewinnard, and Paul Randell

Subjects
Male, medicine.medical_specialty, Evidence-Based Medicine, business.industry, Health Policy, Human immunodeficiency virus (HIV), HIV Infections, Hiv testing, medicine.disease_cause, United Kingdom, HIV Testing, Early Diagnosis, Infectious Diseases, Family medicine, Practice Guidelines as Topic, medicine, Humans, Female, Pharmacology (medical), Sexual Health, Association (psychology), business, Reproductive health
Published
2020

34. Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients

Author

Maria Prendecki, Luke S. P. Moore, Louise Greathead, Paul Randell, Sarah Gleeson, Stephen P. McAdoo, Candice Clarke, Nabeela Mughal, Adam McLean, Eva Santos, Michelle Willicombe, Peter Kelleher, and Mary Guckian

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, Immunosuppression, General Medicine, medicine.disease, Virology, Kidney transplant, Nephrology, Predictive value of tests, biology.protein, Medicine, Antibody, business, Kidney transplantation
Published
2020

35. Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Author

Katrina M. Pollock, Hannah M. Cheeseman, Alexander J. Szubert, Vincenzo Libri, Marta Boffito, David Owen, Henry Bern, Leon R. McFarlane, Jessica O'Hara, Nana-Marie Lemm, Paul McKay, Tommy Rampling, Yee Ting N. Yim, Ana Milinkovic, Cherry Kingsley, Tom Cole, Susanne Fagerbrink, Marites Aban, Maniola Tanaka, Savviz Mehdipour, Alexander Robbins, William Budd, Saul Faust, Hana Hassanin, Catherine A. Cosgrove, Alan Winston, Sarah Fidler, David Dunn, Sheena McCormack, Robin J. Shattock, Kirsty Adams, Fahimah Amini, Nafisah B Atako, Amalina Bakri, Wendy Barclay, Elizabeth Brodnicki, Jonathan C Brown, Ruth Byrne, Rowena Chilvers, Sofia Coelho, Suzanne Day, Monica Desai, Eleanor Dorman, Tamara Elliott, Katie E Flight, James Fletcher, John Galang, Jagruti Gohil, Aneta Gupta, Chris Harlow, Kai Hu, Mohini Kalyan, Dominic Lagrue, Ely Liscano, Cecilia Njenga, Krunal Polra, Derecia A Powlette, Paul Randell, Mary Rauchenberger, Ianto Redknap, Maravic Ricamara, Paul Rogers, Hadijatou Sallah, Karnyart Samnuan, Michael Schumacher, Zareena Shah, Rachel Shaw, Thomas Shaw, Stefan Sivapatham, Susie Slater, Kim Sorley, Regina Storch, Elizabeth Tan, Tricia Tan, Lieze Thielemans, Sarah Whitely, Charlotte Valentine, Jeeva Varghese, Asha Vikraman, Martin Wilkins, The Sir Joseph Hotung Charitable Settlement, and National Institute for Health Research

Subjects
NSP, non-structural protein, medicine.medical_specialty, Medicine (General), Coronavirus disease 2019 (COVID-19), Article, AEs, adverse events, R5-920, Internal medicine, Medicine, Seroconversion, Adverse effect, biology, LNP, lipid nanoparticle, business.industry, GOI, gene of Interest, Immunogenicity, General Medicine, Vaccination, Clinical research, biology.protein, Antibody, business, COVAC1 study Group, saRNA, saRNA, self-amplifying RNA, VEEV, Venezuelan equine encephalitis virus
Abstract

Summary: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0·1-10·0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p

Published
2022

36. Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020

Author

Scott JC Pallett, Rachael Jones, Ahmed Abdulaal, Mitchell A Pallett, Michael Rayment, Aatish Patel, Sarah J Denny, Nabeela Mughal, Maryam Khan, Carolina Rosadas de Oliveira, Panagiotis Pantelidis, Paul Randell, Christofer Toumazou, Matthew K O’Shea, Richard Tedder, Myra O McClure, Gary W Davies, and Luke SP Moore

Subjects
Adult, Science & Technology, Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, Antibodies, Viral, 1117 Public Health and Health Services, Coronavirus, Infectious Diseases, Cross-Sectional Studies, Seroepidemiologic Studies, Virology, Immunoglobulin G, Antibody Formation, London, Spike Glycoprotein, Coronavirus, Humans, Prospective Studies, Life Sciences & Biomedicine, Diagnostics, 0605 Microbiology, 1199 Other Medical and Health Sciences
Abstract

Introduction Immunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear. Aims We aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology. Methods A multicentre prospective cross-sectional study was undertaken (April–July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR. Results We included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2–89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p Conclusion SARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.

Published
2022

37. Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in patients receiving haemodialysis

Author

Katrina Spensley, Sarah Gleeson, Paul Martin, Tina Thomson, Candice L. Clarke, Graham Pickard, David Thomas, Stephen P. McAdoo, Paul Randell, Peter Kelleher, Rachna Bedi, Liz Lightstone, Maria Prendecki, and Michelle Willicombe

Abstract

BackgroundEmerging data suggest a reduction in SARS-CoV-2 vaccine effectiveness against Omicron SARS-CoV-2 infection. There is also evidence to show that Omicron is less pathogenic than previous variants. For clinically vulnerable populations, a less pathogenic variant may still have significant impact on morbidity and mortality. Herein we assess the clinical impact of Omicron infection, and vaccine effectiveness, in an in-centre haemodialysis (IC-HD) population.MethodsOne thousand, one hundred and twenty-one IC-HD patients were included in the analysis, all patients underwent weekly screening for SARS-CoV-2 infection via RT-PCR testing between 1st December 2021 and 16th January 2022. Screening for infection via weekly RT-PCR testing and 3-monthly serological assessment started prior to the vaccine roll out in 2020.ResultsOmicron infection was diagnosed in 145/1121 (12.9%) patients over the study period, equating to an infection rate of 3.1 per 1000 patient days. Vaccine effectiveness (VE) against Omicron infection in patients who had received a booster vaccine was 58 (23-75)%, p=0.002; VE was seen in patients who received either ChAdOx1, VE of 47(2-70)%, p=0.034, or BNT162b2, VE of 66 (36-81)%, p=0.0005, as their first two doses. No protection against infection was seen in patients who were partially vaccinated (2-doses), p=0.83. Prior infection was associated with reduced likelihood of Omicron infection, HR 0.69 (0.50-0.96), p=0.0289. Four (2.8%) patients died within 28 days of infection diagnosis, with no excess mortality was seen in patients with infection.Conclusion3-doses of SARS-CoV-2 vaccines are required in ICHD to provide protection against Omicron infection.

Published
2022

39. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Author

Harry D Wilson, Elaine O'Toole, Andrew Bassett, Moritz U. G. Kraemer, Beth Blane, Scott Goodwin, Giri Shankar, Joseph Hughes, Lucy R. Frost, Alicia Thornton, Scott Elliott, Tammy V Merrill, Sheila Waugh, Alexander Adams, Peter Muir, Graciela Sluga, Rebecca Williams, Hannah Dent, Christophe Fraser, Shavanthi Rajatileka, John C. Hartley, Luke B Snell, Benjamin J Cogger, Lance Turtle, Alex Makunin, John A. Todd, Victoria Wright, Daniela De Angelis, James McKenna, Dinesh Aggarwal, Jonathan K. Ball, Jillian Durham, Garren Scott, Thushan I de Silva, Veena Raviprakash, Hannah M Pymont, Jason Coombes, Anita Lucaci, Luke R. Green, Leigh M Jackson, Hermione J. Webster, Louis du Plessis, David A. Jackson, Minal Patel, Áine O'Toole, Ravi Gupta, Marc Niebel, Garry Scarlett, Rajiv Shah, Guy Mollett, Kathy Li, Rory Gunson, Matthew Bashton, Carl Jones, Sara Kumziene-Summerhayes, Zoltan Molnar, Siona Silveira, Malte L Pinckert, Catherine Ludden, Angeliki Karamani, Leanne Kane, Brendan A I Payne, Alan McNally, Clare M. McCann, Holli Carden, Mohammad Raza, Alison E. Mather, Kate B. Cook, Amy Gaskin, David J. Williams, Shaun R. Seaman, Christopher I. Jones, Gilberto Betancor, Matthew T. G. Holden, Jennifier Liddle, Meera Unnikrishnan, Angie Green, Ben Taylor, Kelly Bicknell, Alexander J. Trotter, Emma Meader, Leanne M Kermack, Nathaniel Storey, Michelle Cronin, Sally Forrest, Sarah Jeremiah, Asad Zaidi, M Morgan, Alasdair MacLean, Thomas R. Connor, Johnathan M Evans, Rachael Stanley, Ryan P George, Nadine Holmes, Richard H. Myers, Christine Sambles, Bernardo Gutierrez, Jeffrey K. J. Cheng, Tim Wyatt, Natasha Jesudason, Lindsay Coupland, Monika Pusok, Manon Ragonnet-Cronin, Jenifer Mason, Joshua Maksimovic, Russell Hope, Alison Holmes, David Simpson, Radoslaw Poplawski, Amelia Joseph, Erwan Acheson, James Bonfield, Mara K. N. Lawniczak, Sascha Ott, Lesley-Anne Williams, Jessica Lynch, Graham P. Taylor, Anita Kenyon, Elizabeth Wastenge, Megan Mayhew, Adhyana I K Mahanama, Stavroula F Louka, Chloe Bishop, Esther Robinson, Darren Smith, Anne M. Presanis, Matthew Carlile, Thomas D Stanton, Dennis Wang, Katerina Galai, Adam P Westhorpe, Flavia Flaviani, Michelle Wantoch, Max Whiteley, Yann Bourgeois, Matthew Gemmell, Mary Ramsay, A Lloyd, Simon Thelwall, Hannah C. Howson-Wells, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Robert Impey, Siddharth Mookerjee, Steven Platt, Emma Swindells, Laura Letchford, Alex Alderton, Lee Graham, Safiah Afifi, David C. Lee, Cassie Breen, Melisa Louise Fenton, Benita Percival, Adrian W Signell, Tanya Golubchik, Ian B Vipond, Eleri Wilson-Davies, Angie Lackenby, Laura Atkinson, Sarojini Pandey, Nazreen F. Hadjirin, Michael A Chapman, Huw Gulliver, Joana Dias, Grant Hall, Antony D Hale, Hassan Hartman, Alp Aydin, Louise Smith, Ashok Dadrah, Johnny Debebe, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Bridget Knight, Hannah E Bridgewater, Nadua Bayzid, Gemma L. Kay, Richard Gregory, Sally Kay, Ellena Brooks, Andre Charlett, Georgina M McManus, Riaz Jannoo, Victoria Blakey, Carol Scott, Rachel Nelson, Liz Ratcliffe, Gerry Tonkin-Hill, Verity Hill, Joanne D. Stockton, Danielle Leek, Steven Leonard, Stephanie Hutchings, Jonathan D. Moore, Kathryn Ann Harris, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Tanzina Haque, Katherine L. Bellis, Khalil Abudahab, Dianne Irish-Tavares, Gaia Nebbia, Kathryn A Jackson, Stephen W Attwood, Daniel Mair, Sreenu Vattipally, Susanne Stonehouse, Ian Merrick, Lucille Rainbow, Mathew A. Beale, Angela Helen Beckett, Ember Hilvers, Thomas Helmer, Jenna Nichols, Giselda Bucca, Salman Goudarzi, Christopher Ruis, Surendra Parmar, Angela Cowell, Alberto C Cerda, Divya K. Shah, Judith Heaney, E. Thomson, Kyriaki Nomikou, Nicole Pacchiarini, Katherine L Harper, Fatima Downing, M. Estée Török, Michelle L Michelsen, Aaron R. Jeffries, Jennifer Collins, Christopher Williams, Katie F. Loveson, Steven Rudder, Theocharis Tsoleridis, Robert Davies, David Robertson, Katherine Smollett, Kathryn McCluggage, Liam Crawford, Inigo Martincorena, Charlotte Beaver, Oliver Megram, Karla Spellman, Sam Haldenby, Emma Betteridge, William D. Fuller, Will P. M. Rowe, Cherian Koshy, Tim E. A. Peto, Alison Cox, Natasha Johnson, Tanya Curran, Sharif Shaaban, Tamyo Mbisa, Cordelia Langford, Eric Witele, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Paul W Bird, Louise Aigrain, Ronan Lyons, Amy Trebes, Sally Corden, Steven Rushton, Jack Cd Lee, Jane Greenaway, Hibo Asad, Amanda Bradley, Mohammed O Hassan-Ibrahim, Shane McCarthy, Fei Sang, Matthew Loose, Hannah Jones, Keith D. James, Chloe L Fisher, Chrystala Constantinidou, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Anna Price, Amy Ash, Michaela John, Alex Zarebski, Fenella D. Halstead, John Danesh, Christine Kitchen, Aminu S Jahun, Mark Whitehead, Julianne R Brown, Catherine Bresner, Marius Cotic, Stefanie V Lensing, Nick Levene, Louissa R Macfarlane-Smith, Wendy Hogsden, Cressida Auckland, Eleanor Drury, Richard Eccles, Jennifer Hart, Seema Nickbakhsh, Alisha Davies, David M. Aanensen, Shirelle Burton-Fanning, Ben Farr, Buddhini Samaraweera, Sarah Wyllie, Hannah Lowe, Richard J. Orton, Martin D. Curran, Carol Churcher, Karen Oliver, Elihu Aranday-Cortes, Wen Yew, Thanh Le-Viet, Matthew Parker, Katherine A Twohig, Shahjahan Miah, Samuel M. Nicholls, G MacIntyre-Cockett, Tranprit Saluja, Charlotte Nelson, Vicki Chalker, Roberto Amato, Ellen Higginson, Timothy M. Freeman, Christopher W Holmes, Yasmin Chaudhry, Elias Allara, Alec Birchley, Iraad Bronner, Emma Moles-Garcia, Angus I. Best, Anna L. Casey, Audrey Farbos, Nicholas W Machin, David W Eyre, Tim Boswell, Charlotte A Williams, Elen De Lacy, Matthew J. Bull, Matilde Mori, Carmen F. Manso, Peijun Zhang, Sahar Eldirdiri, Dimitris Grammatopoulos, Corin Yeats, Claudia Wierzbicki, David G Partridge, Kordo Saeed, Nichola Duckworth, David J. Studholme, Harmeet K Gill, Juan Ledesma, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Husam Osman, Julian A. Hiscox, Helen Adams, Christopher Fearn, Fabrícia F. Nascimento, Ulf Schaefer, James W. Harrison, Andrew J. Nelson, Joshua Quick, Mohammad Tauqeer Alam, Liam Prestwood, Nikos Manesis, Julian Tang, Justin O'Grady, Sophia T Girgis, Louise Berry, Gemma Clark, Marina Escalera Zamudio, Karlie Fallon, Tim J Sloan, Joanne Watkins, Clare Pearson, Andrew D Beggs, Rachel Williams, Luke Bedford, Trevor Robinson, Nicholas M Redshaw, Richard Hopes, Mirko Menegazzo, Katherine Twohig, Gabrielle Vernet, Steven Liggett, Mariateresa de Cesare, Derrick W. Crook, Dominic P. Kwiatkowski, Mark Kristiansen, Miren Iturriza-Gomara, Christopher I. Moore, Claire Cormie, Olivia Boyd, Nikki Smith, Noel Craine, Kathleen A. Williamson, John Boyes, Sian Ellard, Cristina V. Ariani, Wendy Chatterton, David Bonsall, Kevin Lewis, David Jorgensen, Ian Harrison, Christopher Jackson, Martin P McHugh, Danni Weldon, Michael A. Quail, Amita Patel, Lily Geidelberg, Myra Hosmillo, Judith Breuer, Cariad Evans, Edward Barton, Trudy Workman, Derek Fairley, Vineet Patel, Daniel Bradshaw, Robin Manley, Scott Aj Thurston, John Sillitoe, Monique Andersson, Sharon J. Peacock, Jamie Lopez-Bernal, Thomas Thompson, Nabil-Fareed Alikhan, Ben Temperton, Paul Baker, Robin J Moll, Laura Gifford, Nicholas J. Loman, Jayna Raghwani, Jacqui Prieto, Andrew Hesketh, Oliver G. Pybus, Adela Alcolea-Medina, David Buck, Gregory R Young, Alistair C. Darby, Sónia Gonçalves, Aileen G. Rowan, Tabitha Mahungu, Nicholas Ellaby, Jon-Paul Keatley, Lily Tong, Robert Beer, Martyn Guest, Lisa J Levett, Ali R Awan, Iliana Georgana, Paul E Brown, Li Xu-McCrae, Stephen P. Kidd, Sara Rey, Shazaad Ahmad, Danielle C. Groves, Tetyana I. Vasylyeva, David F. Bibby, Nathan Moore, Fiona Ashcroft, Igor Starinskij, Hannah Paul, Claire McMurray, Michael Spencer Chapman, Carlos Balcazar, Joanna Warwick-Dugdale, Pinglawathee Madona, Edith Vamos, Lesley Shirley, Kate Templeton, Luke Foulser, Igor Siveroni, Ewan M. Harrison, Sian Morgan, Diana Rajan, S Taylor, Laia Fina, Naomi Park, Sarah J. O'Brien, Alessandro M Carabelli, Angela Marchbank, Sunando Roy, Leonardo de Oliveira Martins, Steve Palmer, Jonathan Hubb, Alexander J Keeley, Francesc Coll, Malorie Perry, Paul J. Parsons, Anthony Underwood, Patawee Asamaphan, William L Hamilton, Tommy Nyberg, Sophie Palmer, Amanda Symmonds, Anoop Chauhan, Robert Johnson, Christopher J. R. Illingworth, James Shepherd, Wendy Smith, Rich Livett, Rachel Blacow, Margaret Hughes, Jeremy Mirza, Joanne Watts, Jonathan D. Edgeworth, Sarah François, Sue Edwards, Adrienn Angyal, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Paul Randell, Kate Johnson, Eileen Gallagher, Nick Cortes, Yusri Taha, Leah Ensell, Emanuela Pelosi, Stefan Rooke, Michelle Lister, Ana da Silva Filipe, Cassandra S Malone, Themoula Charalampous, Benjamin B Lindsey, Natalie Groves, Colin Smith, Ross J Harris, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Nicola Sheriff, Helen L Lowe, Rachel Jones, Ben Warne, Rose K Davidson, Declan Bradley, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Shirin Aliabadi, Andrew Whitwham, Patrick McClure, Samuel Robson, Sharon Glaysher, Robert J. Munn, Emma L. Wise, Laura Baxter, Kim S Smith, Catherine Moore, Bree Gatica-Wilcox, Alice Broos, Sarah Essex, David Baker, Manjinder Khakh, Dorota Jamrozy, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Robin Howe, Meera Chand, James I. Price, Marina Gourtovaia, Debra Padgett, Jaime Tovar-Corona, Stephen L. Michell, Matthew J. Dorman, Lizzie Meadows, David Heyburn, Iona Willingham, Rocio Martinez Nunez, Grace Taylor-Joyce, Claire M Bewshea, Anita Justice, Simon Cottrell, Rebecca C H Brown, Jamie Young, Gavin Dabrera, Matthew Wyles, Stephen Carmichael, Lisa Berry, Frances Bolt, Andrew Rambaut, Samir Dervisevic, Erik M. Volz, Rahul Batra, Caoimhe McKerr, Samantha McGuigan, Katie Jones, Mailis Maes, Rebecca Dewar, Mary Sinnathamby, Joel Southgate, and Lynn Monaghan

Subjects
medicine.medical_specialty, business.industry, Proportional hazards model, Public health, Hazard ratio, Attendance, C500, Vaccination, Infectious Diseases, Relative risk, Internal medicine, Cohort, medicine, business, Cohort study
Abstract

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Published
2022

40. Stop, think SCORTCH: rethinking the traditional ‘TORCH’ screen in an era of re-emerging syphilis

Author

Hayley Hernstadt, James E. Burns, Justin Penner, Hermione Lyall, and Paul Randell

Subjects
Male, Pediatrics, medicine.medical_specialty, Congenital cytomegalovirus infection, Rubella, 03 medical and health sciences, Neonatal Screening, 0302 clinical medicine, Pregnancy, 030225 pediatrics, medicine, Humans, Syphilis, 030212 general & internal medicine, Pregnancy Complications, Infectious, Chickenpox, business.industry, Decision Trees, Infant, Newborn, Prenatal Care, Hepatitis B, medicine.disease, Toxoplasmosis, Congenital syphilis, Pediatrics, Perinatology and Child Health, Female, business, Malaria
Abstract

BackgroundThe epidemiology of congenital infections is ever changing, with a recent resurgence in syphilis infection rates seen in the UK. Identification of congenital infection is often delayed; early recognition and management of congenital infections is important. Testing modalities and investigations are often limited, leading to missed diagnostic opportunities.MethodsThe SCORTCH (syphilis, cytomegalovirus (CMV), ‘other’, rubella, toxoplasmosis, chickenpox, herpes simplex virus (HSV) and blood-borne viruses) acronym increases the awareness of clinicians to the increased risk of congenital syphilis, while considering other infectious aetiologies including: zika, malaria, chagas disease, parvovirus, enterovirus, HIV, hepatitis B and C, and human T-lymphotropic virus 1, in addition to the classic congenital infections recognised in the ‘TORCH screen’ (toxoplasmosis, ‘other’, rubella, CMV, HSV). The SCORTCH diagnostic approach describes common signs present in infants with congenital infection, details serological testing for mother and infant and important direct diagnostics of the infant. Direct diagnostic investigations include: radiology, ophthalmology, audiology, microbiological and PCR testing for both the infant and placental tissue, the latter also warrants histopathology.ConclusionThe traditional ‘TORCH screen’ focuses on serology-specific investigations, often omits important direct diagnostic testing of the infant, and fails to consider emerging and re-emerging congenital infections. In recognition of syphilis as a re-emerging pathogen and the overlapping clinical presentations of various infectious aetiologies, we advocate for a broader outlook using the SCORTCH diagnostic approach.

Published
2020

41. SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes

Author

Neil S. Graham, Robert McLaren, Loren Cameron, Nicola Lang, David Wingfield, Cornelia Junghans, Shamez N Ladhani, Paul Elliott, Catherine Sendall, David J. Sharp, Paul S. Freemont, Helen Lai, Annie McKirdy, Rawlda Downes, Michael A. Crone, Marta Ciechonska, Paul Randell, Marko Storch, Miles Priestman, Frances Sanderson, Robert Howard, and UK DRI Ltd

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Psychological intervention, Care home, Microbiology, Asymptomatic, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Pandemic, Medicine, Humans, 030212 general & internal medicine, Pandemics, business.industry, Transmission (medicine), SARS-CoV-2, Nursing home, Mortality rate, Outbreak, COVID-19, 1103 Clinical Sciences, Confidence interval, United Kingdom, Nursing Homes, Coronavirus, Diagnostic testing, Infectious Diseases, Emergency medicine, medicine.symptom, Nursing homes, business
Abstract

ObjectivesTo understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents.DesignAn outbreak investigation.Setting4 nursing homes affected by COVID-19 outbreaks in central London.Participants394 residents and 70 staff in nursing homes.InterventionsTwo point-prevalence surveys one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing.Main outcome measuresAll-cause mortality, and mortality attributed to COVID-19 on death certificates. Prevalence of SARS-CoV-2 infection and symptoms in residents and staff.ResultsOverall, 26% (95% confidence interval 22 to 31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70 to 336). Systematic testing identified 40% (95% CI 35 to 46) of residents, of whom 43% (95% CI 34 to 52) were asymptomatic and 18% (95% CI 11 to 24) had atypical symptoms, as well as 4% (95% CI -1 to 9) of asymptomatic staff who tested positive for SARS-CoV-2.ConclusionsThe SARS-CoV-2 outbreak was associated with a very high mortality rate in residents of nursing homes. Systematic testing of all residents and a representative sample of staff identified high rates of SARS-CoV-2 positivity across the four nursing homes, highlighting a potential for regular screening to prevent future outbreaks.

Published
2020

42. Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

Author

Mohammad Raza, Alison E. Mather, Gilberto Betancor, Ian Merrick, Ben Taylor, Mathew A. Beale, Helen Ward, Samir Dervisevic, Michelle Cronin, Aaron R. Jeffries, Louise Smith, Steven Rudder, Mara K. N. Lawniczak, Sascha Ott, Ashok Dadrah, Luke Bedford, Gabrielle Vernet, Erik M. Volz, Rahul Batra, Johnny Debebe, Caoimhe McKerr, Samantha McGuigan, Oliver Megram, Katie Jones, Mailis Maes, Rebecca Dewar, Emma Swindells, Robert E. Johnson, Myra Hosmillo, Wen C Yew, Vineet Patel, Scott Aj Thurston, Matthew Bashton, Luke B Snell, Lynn Monaghan, David Buck, Gregory R Young, Garren Scott, Louis du Plessis, Sara Kumziene-Summerhayes, David M. Aanensen, Carl Jones, Nadine Holmes, Bernardo Gutierrez, Elizabeth Wastenge, Stavroula F Louka, Dennis Wang, Richard I. Gregory, M. Estée Török, Alistair C. Darby, Ulf Schaefer, Marc Niebel, David Robertson, E. Thomson, Carol Churcher, Patrick C McClure, Scott Elliott, Sarah Jeremiah, Katerina Galai, Matthew W. Loose, Megan Mayhew, Adhyana I K Mahanama, Angeliki Karamani, Naomi R Park, David J. Williams, Lance Turtle, Lucy R. Frost, Alicia Thornton, Jennifier Liddle, M Morgan, Tim Wyatt, Paul W Bird, Chloe Bishop, Esther Robinson, Alasdair MacLean, Inigo Martincorena, Bridget A. Knight, Emma Meader, Thomas R. Connor, Hermione J. Webster, Peter Muir, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Hannah E Bridgewater, David Simpson, Radoslaw Poplawski, Angus I. Best, David Baker, Laura Letchford, Cassie Breen, Yann Bourgeois, Matthew Gemmell, Nikki Smith, Alison Holmes, Iliana Georgana, Christophe Fraser, Natasha Jesudason, Johnathan M Evans, Rachael Stanley, Lesley-Anne Williams, Jessica Lynch, Hannah Lowe, Eleri Wilson-Davies, Paul A. Baker, Alex Makunin, James Bonfield, Helen Adams, Christopher Fearn, Peter J. Diggle, Harry D Wilson, Carmen F. Manso, Nichola Duckworth, D Haw, Anna L. Casey, Audrey Farbos, Sam Haldenby, Vicki Chalker, Roberto Amato, Elen De Lacy, Ben Farr, Eric Witele, Buddhini Samaraweera, G MacIntyre-Cockett, Husam Osman, Jane Greenaway, Justin O'Grady, Sally Forrest, Andrew Nelson, Monika Pusok, A Lloyd, Edward Barton, James W. Harrison, Sophie Palmer, Amanda Symmonds, James Shepherd, Nazreen F. Hadjirin, Stephen L. Michell, Mohammed O Hassan-Ibrahim, Fiona Ashcroft, Daniel Mair, Richard H. Myers, Dianne Irish-Tavares, Hannah C. Howson-Wells, Jacqui Prieto, Christine Sambles, Andrew Hesketh, Alp Aydin, Sónia Gonçalves, Tabitha Mahungu, Tanzina Haque, Nicholas Ellaby, Karen Oliver, Hannah Paul, Joanne Watts, Claire McMurray, Lisa J Levett, Darren Smith, Simon Cottrell, Joanna Warwick-Dugdale, Pinglawathee Madona, Matthew J. Dorman, Lizzie Meadows, Ali R Awan, Leanne M Kermack, Jennifer Hart, Angie Lackenby, Carol Scott, Michael Spencer Chapman, Lucille Rainbow, Kyriaki Nomikou, Julianne R Brown, Juan Ledesma, Adam P Westhorpe, Giri Shankar, Karlie Fallon, Tim J Sloan, Joanne Watkins, Robert Impey, Sue Edwards, Rebecca C H Brown, Robin J Moll, Karla Spellman, Laura Gifford, Jamie Young, Adrienn Angyal, Graham Phillip Taylor, Robin Manley, Gavin Dabrera, Michelle Wantoch, Rachel Williams, David Heyburn, Mirko Menegazzo, Derrick W. Crook, Gaia Nebbia, Rachel Nelson, Elaine O'Toole, Luke Foulser, Katherine L Harper, Fatima Downing, Hassan Hartman, Nathan Moore, Gemma L. Kay, Matthew Wyles, Thanh Le-Viet, Edith Vamos, John Sillitoe, Lesley Shirley, Nicholas J. Loman, Iona Willingham, Elihu Aranday-Cortes, Ian B Vipond, Jeremy Mirza, Alberto C Cerda, Michelle L Michelsen, Steven Riley, Alison Cox, Igor Siveroni, Nadua Bayzid, Shavanthi Rajatileka, Giselda Bucca, Benjamin J Cogger, Tim Boswell, Matthew J. Bull, Stephen Carmichael, Lisa Berry, Frances Bolt, Kylie E. C. Ainslie, Martyn Guest, Sarojini Pandey, Katherine L. Bellis, Shane A. McCarthy, Christopher Ruis, Fei Sang, David Bonsall, Danni Weldon, Alex Alderton, Lee Graham, Amy Trebes, Sally Corden, Adrian W Signell, Tanya Golubchik, Huw Gulliver, Rocio Martinez Nunez, Dinesh Aggarwal, Tanya Curran, Jonathan K. Ball, Sharif Shaaban, Paul Randell, Jillian Durham, Alec Birchley, Matilde Mori, Joana Dias, Katherine A Twohig, Grant Hall, Antony D Hale, Alan McNally, Jonathan D. Edgeworth, Safiah Afifi, Andrew Rambaut, Katherine Smollett, David N. Lee, Tamyo Mbisa, Shahjahan Miah, Steven Rushton, Grace Taylor-Joyce, Hannah M Pymont, Chloe L Fisher, Cordelia Langford, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Kathleen A. Williamson, Anna Price, Holli Carden, Khalil Abudahab, Joanne D. Stockton, Meera Unnikrishnan, Jennifer Collins, Emma Moles-Garcia, Michaela John, Christine Kitchen, Tranprit Saluja, Ian Harrison, Lily Tong, Thomas G. Thompson, Thomas Helmer, Amita Patel, Siona Silveira, Deborah Ashby, Claire M Bewshea, Anita Justice, Brendan A I Payne, Alexander J. Trotter, Nikos Manesis, Katie F. Loveson, Cristina V. Ariani, Wendy Chatterton, Robert J. Munn, Julian A. Hiscox, Robert Beer, Judith Breuer, Caroline E. Walters, Liam Crawford, Ara Darzi, Will P. M. Rowe, Cariad Evans, Matthew Parker, Tammy V Merrill, Louise Aigrain, Joshua Quick, Leigh M Jackson, Samuel M. Nicholls, Jonathan W. Moore, John A Hartley, Graham P. Taylor, Cherian Koshy, Shirelle Burton-Fanning, Sheila Waugh, Catherine Moore, Danielle C. Groves, Peijun Zhang, Sahar Eldirdiri, Derek Fairley, Tim E. A. Peto, Jack Cd Lee, Sharon Glaysher, Liam Prestwood, Hannah Dent, Anita Kenyon, Stephen P. Kidd, Nick Levene, Igor Starinskij, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Laia Fina, Angela Marchbank, Daniel Bradshaw, Marina Escalera Zamudio, Scott Goodwin, Andrew D Beggs, Seema Nickbakhsh, Trevor Robinson, Christina Atchison, David K. Jackson, Kathy Li, Rory Gunson, Sunando Roy, Graham S Cooke, Steven Liggett, Yasmin Chaudhry, Anoop Chauhan, Ben Temperton, Mariateresa de Cesare, Paul E Brown, Li Xu-McCrae, Martin P McHugh, Catherine Ludden, Wendy Smith, Danielle Leek, Divya K. Shah, Judith Heaney, Dominic P. Kwiatkowski, Kate M. Johnson, Robin Howe, Malorie Perry, Tetyana I. Vasylyeva, David F. Bibby, Haowei Wang, Steve Palmer, Nicholas W Machin, Charlotte A Williams, Bree Gatica-Wilcox, Angie Green, John A. Todd, Paul Elliott, Noel Craine, Jeffrey K. J. Cheng, Kate Templeton, Jonathan Hubb, Joshua Maksimovic, Christl A. Donnelly, Monique Andersson, Christopher Holmes, Dimitris Grammatopoulos, Christopher B. Williams, David G Partridge, Aminu S Jahun, Alexander Adams, Marius Cotic, Sarah Essex, Christopher J. Moore, Trudy Workman, Nicola Sheriff, Helen L Lowe, Ewan M. Harrison, Dorota Jamrozy, Rachel Jones, Ellen Higginson, Erwan Acheson, Christopher R. Jones, Oliver G. Pybus, Francesc Coll, Sian Morgan, Paul J. Parsons, Patawee Asamaphan, Veena Raviprakash, Andrew R. Bassett, Declan Bradley, Laura Atkinson, Anthony Underwood, Graciela Sluga, Sally Kay, Ellena Brooks, Oliver Eales, Andrew Whitwham, Surendra Parmar, Angela Cowell, Nicole Pacchiarini, Theocharis Tsoleridis, Jason Coombes, Robert Davies, Flavia Flaviani, Benita Percival, Jenna Nichols, Natasha M. Johnson, Salman Goudarzi, Hibo Asad, Amanda Bradley, Hannah Jones, Chrystala Constantinidou, Georgina M McManus, Minal Patel, Steven Leonard, Rebecca Williams Bmbs, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Amy Ash, John Danesh, Corin Yeats, Claudia Wierzbicki, Kordo Saeed, John Boyes, Michael A. Quail, Sharon J. Peacock, Nabil-Fareed Alikhan, Jon-Paul Keatley, Claudio Fronterre, Garry Scarlett, James McKenna, Thushan I de Silva, Malte L Pinckert, Kate B. Cook, Amy Gaskin, Rajiv Shah, Matthew T. G. Holden, Sophie J Prosolek, Nathaniel Storey, Ryan P George, Lindsay Coupland, Jenifer Mason, Matthew Carlile, Thomas D Stanton, Guy Mollett, Siddharth Mookerjee, Mary Ramsay, Steven Platt, Stephen W Attwood, Susanne Stonehouse, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Mark Whitehead, Catherine Bresner, Stefanie V Lensing, Louissa R Macfarlane-Smith, Colin P. Smith, Wendy Hogsden, Charlotte Nelson, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Samuel Robson, Zoltán Molnár, Emma L. Wise, Sian Ellard, Kim S Smith, Alice Broos, Manjinder Khakh, Kathryn A Jackson, Claire Cormie, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Meera Chand, Debra Padgett, Cassandra S Malone, James V. Price, Themoula Charalampous, Ronan A Lyons, Natalie Groves, Stefan Rooke, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Michelle Lister, Carlos Balcazar, Ana da Silva Filipe, Ben Warne, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Rose K Davidson, Angela Helen Beckett, Ember Hilvers, Kathryn McCluggage, Eileen Gallagher, Charlotte Beaver, Nick Cortes, Alisha Davies, Yusri Taha, Leah Ensell, Emanuela Pelosi, Elias Allara, Cressida Auckland, Eleanor Drury, Richard Eccles, Adela Alcolea-Medina, William L Hamilton, Rich Livett, Rachel Blacow, Margaret Hughes, Sarah François, Melisa Louise Fenton, Liz Ratcliffe, Verity Hill, Stephanie Hutchings, Kathryn Ann Harris, Emma Betteridge, William D. Fuller, Sophia T Girgis, Louise Berry, Gemma Clark, Nicholas M Redshaw, Richard Hopes, Leonardo de Oliveira Martins, Alexander J Keeley, Beth Blane, Wendy S. Barclay, Victoria Wright, Anita Lucaci, Luke R. Green, Fenella D. Halstead, Sarah Wyllie, Iraad F. Bronner, Áine O'Toole, Ravi Gupta, Leanne Kane, Clare M. McCann, Michael R Chapman, David W Eyre, Kelly Bicknell, Aileen G. Rowan, Sara Rey, Shazaad Ahmad, Diana Rajan, S Taylor, Sarah J. O'Brien, Alessandro M Carabelli, Amelia Joseph, Max Whiteley, Riaz Jannoo, Victoria Blakey, Martin D. Curran, David J. Studholme, Harmeet K Gill, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Julian Tang, Clare Pearson, Mark Kristiansen, Miren Iturriza-Gomara, National Institute for Health Research, and UK Research and Innovation

Subjects
Delta, Adult, Male, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Vaccination Coverage, Coronavirus disease 2019 (COVID-19), Adolescent, General Science & Technology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Vaccine Efficacy, Biology, Young Adult, Exponential growth, Ethnicity, Prevalence, Humans, Child, Aged, Family Characteristics, Multidisciplinary, High prevalence, COVID-19 Genomics UK (COG-UK) Consortium11‡, SARS-CoV-2, Age Factors, COVID-19, Middle Aged, Virology, Hospitalization, England, Socioeconomic Factors, COVID-19 Nucleic Acid Testing, Child, Preschool, Female, Self Report
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

Published
2021

43. Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study

Author

Zoey Herm, Michael A. Crone, Loren Perelman, Arthi Anand, Paul Randell, Panagiotis Pantelidis, Paul S. Freemont, and Saghar Missaghian-Cully

Subjects
Computer science, SARS-CoV-2, Pooling, Staffing, Medicine (miscellaneous), Articles, diagnostics, laboratory automation, SARS-CoV-2, RT-qPCR, General Biochemistry, Genetics and Molecular Biology, Group testing, Technical feasibility, Workflow, Resource (project management), Risk analysis (engineering), Proof of concept, Laboratory automation, diagnostics, laboratory automation, Research Article
Abstract

Background: Diagnostic laboratories are currently required to provide routine testing of asymptomatic staff and patients as a part of their clinical screening for SARS-CoV-2 infection. However, these cohorts display very different disease prevalence from symptomatic individuals and testing capacity for asymptomatic screening is often limited. Group testing is frequently proposed as a possible solution to address this; however, proposals neglect the technical and operational feasibility of implementation in a front-line diagnostic laboratory. Methods: Between October and December 2020, as a seven-week proof of concept, we took into account scientific, technical and operational feasibility to design and implement an adaptive pooling strategy in an NHS diagnostic laboratory in London (UK). We assessed the impact of pooling on analytical sensitivity and modelled the impact of prevalence on pooling strategy. We then considered the operational constraints to model the potential gains in capacity and the requirements for additional staff and infrastructure. Finally, we developed a LIMS-agnostic laboratory automation workflow and software solution and tested the technical feasibility of our adaptive pooling workflow. Results: First, we determined the analytical sensitivity of the implemented SARS-CoV-2 assay to be 250 copies/mL. We then determined that, in a setting with limited analyser capacity, the testing capacity could be increased by two-fold with pooling, however, in a setting with limited reagents, this could rise to a five-fold increase. These capacity increases could be realized with modest additional resource and staffing requirements whilst utilizing up to 76% fewer plastic consumables and 90% fewer reagents. Finally, we successfully implemented a plate-based pooling workflow and tested 920 patient samples using the reagents that would usually be required to process just 222 samples. Conclusions: Adaptive pooled testing is a scientifically, technically and operationally feasible solution to increase testing capacity in frontline NHS diagnostic laboratories.

Published
2021

44. Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients

Author

Andrew I. Ritchie, Owais Kadwani, Dina Saleh, Behrad Baharlo, Lesley R. Broomhead, Paul Randell, Umeer Waheed, Maie Templeton, Elizabeth Brown, Richard Stümpfle, Parind Patel, Stephen J. Brett, Sanooj Soni, The Academy of Medical Sciences, and British Journal of Anaesthesia

Subjects
Adult, Respiratory Distress Syndrome, Multidisciplinary, Critical Care, General Science & Technology, SARS-CoV-2, COVID-19, Humans, Prospective Studies, Retrospective Studies
Abstract

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p

Published
2021

45. Development of a Multiplex Tandem PCR (MT-PCR) Assay for the Detection of Emerging SARS-CoV-2 Variants

Author

Luke B. Snell, Cheryl Williams, Samir Dervisevic, Saidat A R T Ebie, Keith Stanley, Paul Randell, Penelope R. Cliff, Lindsay Coupland, Marcus Pond, Richard S. Hale, Joel Paul, and Peter Crowley

Subjects
Sequence analysis, Computational biology, Genome, Viral, Biology, Microbiology, Polymorphism, Single Nucleotide, Sensitivity and Specificity, DNA sequencing, law.invention, in vitro diagnostic test, law, Virology, Multiplex polymerase chain reaction, Humans, Multiplex, Typing, Polymerase chain reaction, Whole genome sequencing, variants, Whole Genome Sequencing, SARS-CoV-2, Communication, COVID-19, Nucleic acid amplification technique, QR1-502, Infectious Diseases, COVID-19 Nucleic Acid Testing, Spike Glycoprotein, Coronavirus, Multiplex Polymerase Chain Reaction, Nucleic Acid Amplification Techniques
Abstract

The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (

Published
2021

47. SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study

Author

Steven Riley, Graham S Cooke, Paul Elliott, Paul Randell, Maria Prendecki, Candice Clarke, Alexandra H C Cann, Maya Moshe, Michelle Willicombe, Wendy S. Barclay, Peter Kelleher, Jonathan Brown, Helen Ward, Tina Thomson, Deborah Ashby, Ara Darzi, and Anjna Badhan

Subjects
medicine.medical_specialty, biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Diagnostic accuracy, Serology, Vaccination, Internal medicine, Cohort, medicine, biology.protein, Outpatient clinic, Sampling (medicine), Antibody, business
Abstract

BackgroundLateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine.MethodsThis is a prospective diagnostic accuracy study.SettingSampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities.ParticipantsTwo cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected.InterventionsDuring the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.Main outcome measuresThe accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay.ResultsUsing the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard.ConclusionsFortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.

Published
2021

48. 4 Early identification of high-risk individuals for combination monoclonal antibody therapy is feasible by SARS-CoV-2 anti-spike antibody specific lateral flow assay

Author

Scott JC Pallett, Michael Rayment, Paul Randell, Gary W Davies, and Luke SP Moore

Subjects
General Medicine
Abstract

BackgroundCombination monoclonal antibody therapy has recently been approved for prevention and treatment of severe COVID-19 infection in the UK. Available data suggests benefit is limited to those yet to mount an effective immune response from natural infection or vaccination, but concern exists around ability to make timely assessment of immune status of community-based patients.MethodsHealthcare workers were invited to undergo paired laboratory-based and rapid point-of- care (POC) lateral flow anti-spike antibody testing. Three commercial POC tests were selected to represent currently available testing methods: a split IgM/IgG anti-spike antibody test, an anti-receptor binding domain total antibody test and an anti-spike neutralisation assay. Qualitative POC colourmetric band intensities were independently scored and correlated with quantitative IgG neutralising antibody titres (Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle immunoassay [CMIA]). CMIA titres were correlated with the World Health Organisation international reference standard for neutralising antibody. Negative controls were carried out using 2018 pre-pandemic sera and post-pandemic individuals with negative CMIA results (target population).Results190 individuals (median 40 years, IQR 29-49; 76.2% female) underwent paired testing, with a further 40 pre-pandemic sera tested. Assays demonstrated high performance characteristics: split IgM/IgG assay sensitivity 96.2% (95%CI 92.4.5–98.5), specificity 100.0% (95%CI 91.8–100.0); anti-receptor binding domain total antibody assay sensitivity 100.0% (95%CI 95.5–100.0), specificity 100.0% (95%CI 69.2–100.0). The neutralising antibody assay had a specificity of 97.0% (95%CI 84.2–99.9%) and strongly correlated with neutralising antibody titre (p99%.ConclusionsPOC assays were found to be reliable predictors of both antibody status and broadly of neutralising antibody titre. Anti-S POC assays have potential to act as suitable alternatives for rapid identification of community patient immune status at presentation.

Published
2022

49. SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men

Author

Sophie J. Weller, Eleri Wilson-Davies, José Afonso Guerra-Assunção, Beatrix Kele, Andrew Hayward, Joseph Hughes, Sharon Glaysher, Luke B Snell, Themoula Charalampous, da Silva Filipe A, Irene M. Monahan, Matthew Parker, Cassie F Pope, Kordo Saeed, Teresa Cutino-Moguel, Oliver Stirrup, Alison Holmes, Angela H. Becket, Rachel Williams, David G Partridge, Gaia Nebbia, Guy Mollett, Tabassum Khan, Samuel Robson, Phillip Wade, Andrew Copas, Adam A. Witney, Judith Breuer, Cristina Venturini, Nick Freemantle, Price, de Silva Ti, Raghavendran Kulasegara-Shylini, E. Thomson, Tabitha Mahungu, Paul Randell, Sunando Roy, Joshua F. Taylor, Florencia A T Boshier, Emanuela Pelosi, and Adela Alcolea-Medina

Subjects
Pregnancy, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Transmission (medicine), Proportional hazards model, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hazard ratio, medicine.disease, Disease severity, Internal medicine, Intensive care, Medicine, business
Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented.MethodsWe collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16/11/2020 - 10/01/2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity.ResultsSequences were obtained from 2341 inpatients (HOCI cases = 786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The hazard ratio (HR) for mortality of B.1.1.7 compared to other lineages was 1.01 (95% CI 0.79-1.28, P=0.94) and for ITU admission was 1.01 (95% CI 0.75-1.37, P=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95-1.78) and ITU admission (HR 1.82, 95% CI 1.15-2.90) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61-1.10; ITU HR 0.74, 95% CI 0.52-1.04).ConclusionsIn common with smaller studies of patients hospitalised with SARS-CoV-2 we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared to other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.

Published
2021

50. Reliability of Spike Gene Target Failure for ascertaining SARS-CoV-2 lineage B.1.1.7 prevalence in a hospital setting

Author

José Afonso Guerra-Assunção, Michael A. Crone, Judith Breuer, Tabitha Mahungu, Juanita Pang, Paul Randell, Florencia A.T. Boshier, and Paul S. Freemont

Subjects
Whole genome sequencing, Lineage (genetic), Hospital setting, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Spike Protein, Lower cost, Spike (software development), Computational biology, Biology, Gene
Abstract

The appearance of the SARS-CoV-2 lineage B.1.1.7 in the UK in late 2020, associated with faster transmission, sparked the need to find effective ways to monitor its spread. The set of mutations that characterise this lineage include a deletion in position 69 and 70 of the spike protein, which is known to be associated with Spike Gene Target Failure (SGTF) in a commonly used three gene diagnostic qPCR assay. The lower cost and faster turnaround times compared to whole genome sequencing make the use of qPCR for monitoring of the variant spread an attractive proposition. However, there are several potential issues with this approach. Here we use 826 SARS-CoV-2 samples collected in a hospital setting as part of the Hospital Onset COVID Infection (HOCI) study where qPCR was used for viral detection, followed by whole genome sequencing (WGS), to identify the factors to consider when using SGTF to infer lineage B.1.1.7 prevalence in a hospital setting, with potential implications for locations where this variant has recently been introduced.

Published
2021

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