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1. Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Author

Keith Siew, Kevin A. Nestler, Charlotte Nelson, Viola D’Ambrosio, Chutong Zhong, Zhongwang Li, Alessandra Grillo, Elizabeth R. Wan, Vaksha Patel, Eliah Overbey, JangKeun Kim, Sanghee Yun, Michael B. Vaughan, Chris Cheshire, Laura Cubitt, Jessica Broni-Tabi, Maneera Yousef Al-Jaber, Valery Boyko, Cem Meydan, Peter Barker, Shehbeel Arif, Fatemeh Afsari, Noah Allen, Mohammed Al-Maadheed, Selin Altinok, Nourdine Bah, Samuel Border, Amanda L. Brown, Keith Burling, Margareth Cheng-Campbell, Lorianna M. Colón, Lovorka Degoricija, Nichola Figg, Rebecca Finch, Jonathan Foox, Pouya Faridi, Alison French, Samrawit Gebre, Peter Gordon, Nadia Houerbi, Hossein Valipour Kahrood, Frederico C. Kiffer, Aleksandra S. Klosinska, Angela Kubik, Han-Chung Lee, Yinghui Li, Nicholas Lucarelli, Anthony L. Marullo, Irina Matei, Colleen M. McCann, Sayat Mimar, Ahmed Naglah, Jérôme Nicod, Kevin M. O’Shaughnessy, Lorraine Christine De Oliveira, Leah Oswalt, Laura Ioana Patras, San-huei Lai Polo, María Rodríguez-Lopez, Candice Roufosse, Omid Sadeghi-Alavijeh, Rebekah Sanchez-Hodge, Anindya S. Paul, Ralf Bernd Schittenhelm, Annalise Schweickart, Ryan T. Scott, Terry Chin Choy Lim Kam Sian, Willian A. da Silveira, Hubert Slawinski, Daniel Snell, Julio Sosa, Amanda M. Saravia-Butler, Marshall Tabetah, Erwin Tanuwidjaya, Simon Walker-Samuel, Xiaoping Yang, Yasmin, Haijian Zhang, Jasminka Godovac-Zimmermann, Pinaki Sarder, Lauren M. Sanders, Sylvain V. Costes, Robert A. A. Campbell, Fathi Karouia, Vidya Mohamed-Alis, Samuel Rodriques, Steven Lynham, Joel Ricky Steele, Sergio Baranzini, Hossein Fazelinia, Zhongquan Dai, Akira Uruno, Dai Shiba, Masayuki Yamamoto, Eduardo A.C.Almeida, Elizabeth Blaber, Jonathan C. Schisler, Amelia J. Eisch, Masafumi Muratani, Sara R. Zwart, Scott M. Smith, Jonathan M. Galazka, Christopher E. Mason, Afshin Beheshti, and Stephen B. Walsh

Subjects
Science
Abstract

Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.

Published
2024
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2. SARS-CoV-2 detection by a clinical diagnostic RT-LAMP assay [version 2; peer review: 2 approved]

Author

Michael D. Buck, Enzo Z. Poirier, Ana Cardoso, Bruno Frederico, Johnathan Canton, Sam Barrell, Rupert Beale, Richard Byrne, Simon Caidan, Margaret Crawford, Laura Cubitt, Sonia Gandhi, Robert Goldstone, Paul R. Grant, Kiran Gulati, Steve Hindmarsh, Michael Howell, Michael Hubank, Rachael Instrell, Ming Jiang, George Kassiotis, Wei-Ting Lu, James I. MacRae, Iana Martini, Davin Miller, David Moore, Eleni Nastouli, Jerome Nicod, Luke Nightingale, Jessica Olsen, Amin Oomatia, Nicola O'Reilly, Anett Rideg, Ok-Ryul Song, Amy Strange, Charles Swanton, Samra Turajlic, Mary Wu, Caetano Reis e Sousa, and The Crick COVID-19 Consortium

Subjects
Medicine, Science
Abstract

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARS-CoV-2 detection by RT-LAMP that is robust, reliable, repeatable, specific, and inexpensive.

Published
2021
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3. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Author

Lisa Pickering, Richard Stone, Ian Chau, James I. MacRae, Karla Lingard, Susana Banerjee, Barry Ward, Jessica Bazin, William Gordon, Naureen Starling, Katalin A. Wilkinson, Mary O'Brien, Anna Robinson, Joanne Droney, Sacheen Kumar, Emma Nicholson, Martin Pule, Isla Leslie, Andreas M. Schmitt, Ambrosius P. Snijders, Karolina Rzeniewicz, Emma Nye, Benjamin Shum, Mary Mangwende, Scott Shepherd, Nalinie Joharatnam-Hogan, Robyn L. Shea, Michael Howell, Anthony J. Swerdlow, Shaman Jhanji, Simon Caidan, Eleanor Carlyle, Laura Amanda Boos, Annika Fendler, Kevin W. Ng, Kate Tatham, Leila Mekkaoui, Tim Slattery, Margaret Crawford, Firza Gronthoud, Philip Hobson, Camila Gomes, Robert J. Wilkinson, Jerome Nicod, Charles Swanton, Mike Gavrielides, Kim Edmonds, Robin L. Jones, Fiona Byrne, Laura Cubitt, Alison Reid, Lucy Holt, Ana Agua-Doce, Ruth Harvey, Sarah Sarker, Spyridon Gennatas, Camille L. Gerard, Andrew Furness, Hamid Ahmod, Liam Welsh, Nicholas van As, Olivia Curtis, Nadia Yousaf, Mary Wu, Nicholas C. Turner, Christina Messiou, David Cunningham, Zayd Tippu, Georgina H. Cornish, Sonia Gandhi, Helen R. Flynn, Harshil Patel, Yasir Khan, James Larkin, Lewis Au, George Kassiotis, Samra Turajlic, Maddalena Cerrone, Clemency Stephenson, Steve Gamblin, Kate Young, Wenyi Xie, Shreerang Bhide, Robert L. Goldstone, Alicia Okines, Kevin J. Harrington, Lyra Del Rosario, and Wellcome Trust

Subjects
Cancer Research, IMPACT, Antibody Response, Alpha (ethology), CORONAVIRUS DISEASE 2019, Disease, Adaptive Immunity, Article, Immune system, SEROCONVERSION, Medicine, Neutralizing antibody, Cancer, Science & Technology, biology, SARS-CoV-2, business.industry, MORTALITY, COVID-19, medicine.disease, Titer, SEVERITY, Oncology, Immunology, Cohort, biology.protein, Prospective Study, Antibody, business, Neutralising Antibodies, Vaccine, Life Sciences & Biomedicine, T-cell Response
Abstract

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Published
2022
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4. Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

Author

Simona Balestrini, Matthias J. Koepp, Sonia Gandhi, Hannah M. Rickman, Gee Yen Shin, Catherine F. Houlihan, Jonny Anders-Cannon, Katri Silvennoinen, Fenglai Xiao, Sara Zagaglia, Kirsty Hudgell, Mariusz Ziomek, Paul Haimes, Adam Sampson, Annie Parker, J. Helen Cross, Rosemarie Pardington, Eleni Nastouli, Charles Swanton, Josemir W. Sander, Sanjay M. Sisodiya, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Rupert Beale, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J. Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D. Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Matthew Byott, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Peter Cherepanov, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C. Driscoll, Annalisa D'Avola, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Daniel Frampton, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Steve Gamblin, Kathleen Gärtner, Liam Gaul, Helen M. Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R. Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G. Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Emine Hatipoglu, Lyn Healy, Judith Heaney, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R. Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, George Kassiotis, Gavin Kelly, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon Wing Liu, Sam Loughlin, Wei-Ting Lu, James I. MacRae, Akshay Madoo, Julie A. Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M. Matz, Samuel McCall, Laura E. McCoy, Fiona McKay, Edel C. McNamara, Carlos M. Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, David Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D. O'Leary, Jessica Olsen, Olga O'Neill, Nicola O'Reilly, Paula Ordonez Suarez, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Stavroula M Paraskevopoulou, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S. Perrault, Abigail Perrin, Roy Poh, Enzo Z. Poirier, James M. Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Fiona Roberts, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Emilie Sanchez, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A. Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Rajvee Shah Punatar, Maryam Shahmanesh, Joe Shaw, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M. Snell, Ok-Ryul Song, Moira J. Spyer, Louisa Steel, Amy Strange, Adrienne E. Sullivan, Michele S.Y. Tan, Zoe H. Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B. Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C. Tsai, James M.A. Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P. Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A. Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Williams, Matthew J. Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A. Zagalak, Davide Zecchin, Rachel Zillwood, Santhakumari Carthiyaniamma, Jane DeTisi, Julie Dick, Andrea Hill, Karin Kipper, Birinder Kullar, Sarah Norris, Fergus Rugg-Gunn, Rebecca Salvatierra, Gabriel Shaya, Astrid Sloan, Priyanka Singh, James Varley, Ben Whatley, and Academic Medical Center

Subjects
Male, Pediatrics, CCC, Crick COVID Consortium, SWGC, Sir William Gowers Centre, Comorbidity, Residential Facilities, Cohort Studies, Behavioral Neuroscience, Epilepsy, 0302 clinical medicine, Case fatality rate, Infection control, 030212 general & internal medicine, Care Models, COVID-19, coronavirus disease 2019, Aged, 80 and over, Surveillance, Middle Aged, 3. Good health, Treatment Outcome, Neurology, UCLH, University College London Hospitals NHS Foundation Trust, PEG, percutaneous endoscopic gastrostomy, STE, St Elizabeth’s Centre, Female, medicine.symptom, PPE, personal protective equipment, Cohort study, Adult, medicine.medical_specialty, Isolation (health care), Clinical Neurology, Asymptomatic, Article, Young Adult, 03 medical and health sciences, medicine, Humans, YE, Young Epilepsy, Aged, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Infection Control, business.industry, SARS-CoV-2, Prevention, Vulnerable people, COVID-19, TM, The Meath, medicine.disease, Long-Term Care, CCE, Chalfont Centre for Epilepsy, United Kingdom, Long-term care, Neurology (clinical), business, 030217 neurology & neurosurgery, Contact tracing
Abstract

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Published
2021

5. SARS-CoV-2 detection by a clinical diagnostic RT-LAMP assay

Author

Jerome Nicod, James I. MacRae, Amin Oomatia, Laura Cubitt, Iana Martini, Simon Caidan, Kiran Gulati, Sonia Gandhi, Luke Nightingale, Michael D. Buck, Enzo Z. Poirier, Wei-Ting Lu, Margaret Crawford, Nicola O’Reilly, Amy Strange, Michael Howell, Steve Hindmarsh, Charles Swanton, Jessica Olsen, Samra Turajlic, George Kassiotis, Paul Grant, Rupert Beale, Caetano Reis e Sousa, Mary Wu, Ming Jiang, Robert L. Goldstone, Sam Barrell, Eleni Nastouli, Rachael Instrell, Bruno Frederico, Davin Miller, Anett Rideg, Ana Cardoso, Ok-Ryul Song, Johnathan Canton, Mike Hubank, David Moore, and Richard D. Byrne

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Pandemic, Medicine, Medical physics, Viral rna, Diagnostic laboratory, Intensive care medicine, License, RT-LAMP, business.industry, SARS-CoV-2, Diagnostic test, Creative commons, Articles, Method Article, 3. Good health, 030104 developmental biology, business, clinical diagnostic
Abstract

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARSCoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive © 2021. Buck MD et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Published
2021

6. Standard operating procedures for SARS-CoV-2 detection by a clinical diagnostic RT-LAMP assay

Author

Kiran Gulati, Amy Strange, Laura Cubitt, Ana Cardoso, Charles Swanton, Jerome Nicod, Mike Hubank, Margaret Crawford, David Moore, James I. MacRae, Enzo Z. Poirier, Amin Oomatia, Simon Caidan, Eleni Nastouli, Robert J. Goldstone, Richard D. Byrne, Sam Barrell, Philip A. Walker, Wei-Ting Lu, Michael Howell, Caetano Reis e Sousa, Ming Jiang, Michael D. Buck, Steve Hindmarsh, Sonia Gandhi, Jessica Olsen, Davin Miller, Mary Wu, Anett Rideg, Steve Gamblin, Ok-Ryul Song, Rachael Instrell, George Kassiotis, Johnathan Canton, Paul Grant, Bruno Frederico, Nicola O’Reilly, Rupert Beale, Iana Martini, Luke Nightingale, and Samra Turajlic

Subjects
medicine.medical_specialty, business.industry, Operating procedures, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, Diagnostic test, Medical physics, Viral rna, Diagnostic laboratory, business, Standard operating procedure
Abstract

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 40,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated standard operating procedure (SOP) for high-throughput SARS-CoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

Published
2020

7. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers

Author

Catherine F Houlihan, Nina Vora, Thomas Byrne, Dan Lewer, Gavin Kelly, Judith Heaney, Sonia Gandhi, Moira J Spyer, Rupert Beale, Peter Cherepanov, David Moore, Richard Gilson, Steve Gamblin, George Kassiotis, Laura E McCoy, Charles Swanton, Andrew Hayward, Eleni Nastouli, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Annalisa D'Avola, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C Driscoll, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Liam Gaul, Helen M Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Lyn Healy, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon-Wing Liu, Sam Loughlin, Wei-Ting Lu, James I MacRae, Akshay Madoo, Julie A Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M Matz, Samuel McCall, Fiona McKay, Edel C McNamara, Carlos M Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D O'Leary, Jessica Olsen, Olga O'Neill, Paula Ordonez Suarez, Nicola O'Reilly, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S Perrault, Abigail Perrin, Roy Poh, Enzo Z Poirier, James M Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Rajvee Shah Punatar, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Joe Shaw, Gee Yen Shin, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M Snell, Ok-Ryul Song, Louisa Steel, Amy Strange, Adrienne E Sullivan, Michele SY Tan, Zoe H Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C Tsai, James MA Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Wiliams, Matthew J Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A Zagalak, Davide Zecchin, Rachel Zillwood, Rebecca Matthews, Abigail Severn, Sajida Adam, Louise Enfield, Angela McBride, Kathleen Gärtner, Sarah Edwards, Fabiana Lorencatto, Susan Michie, Ed Manley, Maryam Shahmanesh, Hinal Lukha, Paulina Prymas, Hazel McBain, Robert Shortman, Leigh Wood, Claudia Davies, Bethany Williams, Kevin W Ng, Georgina H Cornish, Nikhil Faulkner, Andrew Riddell, Philip Hobson, Ana Agua-Doce, Kerol Bartolovic, Emma Russell, Lotte Carr, Emilie Sanchez, Daniel Frampton, Matthew Byott, Stavroula M Paraskevopoulou, Elise Crayton, Carly Meyer, Triantafylia Gkouleli, Andrea Stoltenberg, Veronica Ranieri, Tom Byrne, Fiona Roberts, and Emine Hatipoglu

Subjects
Adult, 2019-20 coronavirus outbreak, Infectious Disease Transmission, Patient-to-Professional, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, Pneumonia, Viral, Viral transmission, Antibodies, Viral, Risk Assessment, Article, Betacoronavirus, Environmental health, Occupational Exposure, Pandemic, Health care, London, Medicine, Humans, Prospective Studies, Seroconversion, Pandemics, Cross Infection, business.industry, SARS-CoV-2, COVID-19, General Medicine, Occupational exposure, business, Coronavirus Infections
Published
2020

8. Scalable and robust SARS-CoV-2 testing in an academic center

Author

Jim, Aitken, Karen, Ambrose, Sam, Barrell, Rupert, Beale, Ganka, Bineva-Todd, Dhruva, Biswas, Richard, Byrne, Simon, Caidan, Peter, Cherepanov, Laura, Churchward, Graham, Clark, Margaret, Crawford, Laura, Cubitt, Vicky, Dearing, Christopher, Earl, Amelia, Edwards, Chris, Ekin, Efthymios, Fidanis, Alessandra, Gaiba, Steve, Gamblin, Sonia, Gandhi, Jacki, Goldman, Robert, Goldstone, Paul R, Grant, Maria, Greco, Judith, Heaney, Steve, Hindmarsh, Catherine F, Houlihan, Michael, Howell, Michael, Hubank, Deborah, Hughes, Rachael, Instrell, Deborah, Jackson, Mariam, Jamal-Hanjani, Ming, Jiang, Mark, Johnson, Leigh, Jones, Nnennaya, Kanu, George, Kassiotis, Stuart, Kirk, Svend, Kjaer, Andrew, Levett, Lisa, Levett, Marcel, Levi, Wei-Ting, Lu, James I, MacRae, John, Matthews, Laura E, McCoy, Catherine, Moore, David, Moore, Eleni, Nastouli, Jerome, Nicod, Luke, Nightingale, Jessica, Olsen, Nicola, O'Reilly, Amar, Pabari, Venizelos, Papayannopoulos, Namita, Patel, Nigel, Peat, Marc, Pollitt, Peter, Ratcliffe, Caetano, Reis E Sousa, Annachiara, Rosa, Rachel, Rosenthal, Chloe, Roustan, Andrew, Rowan, Gee Yen, Shin, Daniel M, Snell, Ok-Ryul, Song, Moira J, Spyer, Amy, Strange, Charles, Swanton, James M A, Turner, Melanie, Turner, Andreas, Wack, Philip A, Walker, Sophia, Ward, Wai Keong, Wong, Joshua, Wright, Mary, Wu, and Rachel, Zillwood

Subjects
Europe, COVID-19 Testing, Medical research, Clinical Laboratory Techniques, Reverse Transcriptase Polymerase Chain Reaction, Academies and Institutes, Medical Laboratory Science, Health care, Humans, Coronavirus Infections, Author Correction, United Kingdom
Published
2020

9. Scalable and Resilient SARS-CoV-2 testing in an Academic Centre

Author

Charles Swanton, James I. MacRae, Nnennaya Kanu, Steve Hindmarsh, Karen Ambrose, Andrew Levett, Judith Heaney, Maria Greco, Christopher Earl, Stuart Kirk, Rachel Instrell, Simon Caidan, Peter Cherepanov, Vicky Dearing, Wei-Ting Lu, Laura E. McCoy, George Kassiotis, Mary Wu, Amelia Edwards, Andrew Rowan, Michael Howell, Jessica Olsen, Venizelos Papayannopoulos, Amar Pabari, Caetano Reis e Sousa, Wai Keong Wong, Nicola O’Reilly, Marc Pollitt, Jerome Nicod, Philip A. Walker, Ming Jiang, Marg Crawford, Ganka Bineva-Todd, Alessandra Gaiba, Melanie Turner, Jacki Goldman, James M. A. Turner, Chloe Roustan, Sonia Gandhi, Catherine Moore, Nigel Peat, Rachel Rosenthal, John N. S. Matthews, Amy Strange, Chris Ekin, Marcel Levi, Richard D. Byrne, Laura Churchward, Steve Gamblin, Graham Clark, Jim Aitken, Deb Jackson, Mark Johnson, Svend Kjaer, Joshua Wright, Annachiara Rosa, Andreas Wack, Ok-Ryul Song, Laura Cubitt, Mariam Jamal-Hanjani, David Moore, Leigh Jones, Debbie Hughes, Paul Grant, Sophie Ward, Efthymios Fidanis, Namita Patel, Eleni Nastouli, Dhruva Biswas, Gee Yen Shin, Daniel M Snell, Mike Hubank, Lisa Levett, Moria Spyer, Peter J. Ratcliffe, Luke Nightingale, Sam Barrell, Rupert Beale, Robert L. Goldstone, and Catherine F Houlihan

Subjects
0303 health sciences, business.industry, Computer science, medicine.disease, Pipeline (software), Turnaround time, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Health care, Scalability, Pandemic, medicine, Web application, 030212 general & internal medicine, Medical emergency, Diagnostic laboratory, business, Bespoke, 030304 developmental biology
Abstract

The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.

Published
2020

10. Kit-free automated RNA extraction for SARS-CoV-2 testing v1

Author

Maria Greco, Efthymios Fidanis, Amelia Edwards, Margaret Crawford, Laura Cubitt, Sophia Ward, Robert Goldstone, Nnenna Kanu, James MacRae, Michael Hubank, and Jerome Nicod

Subjects
Protocol (science), Computer science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), RNA extraction, Virology
Abstract

Purpose of examination / Clinical relevance At the end of 2019, several pneumonia cases were reported in Wuhan, China and the pathogen was confirmed as a new viral strain. World Health organization has named the newly identified coronavirus as 2019-nCoV, also known as SARS-Cov-2. The disease developed into a dangerous pandemic, posing major challenges to the NHS. Although more research is necessary to better understand the virus, in response to the emergency, simple and rapid testing is essential to identify the virus in infected individuals. This will aid the implementation of efficient interventions to contain the spread, and distinguish healthcare workers who have been infected, and are required to self-isolate, from those showing similar symptoms but which are not 2019-nCoV associated. The latter category may continue to work, alleviating stress on hard-pressed healthcare resources. 2019-nCoV is an RNA virus, and the diagnostic tests detect viral RNA in swabs from patient airways using a reverse transcriptase PCR assay. Samples are submitted to HSL, an accredited reporting laboratory, and transferred to the Crick for testing. The first step of the process is sample receipt at the Crick. This SOP describes the extraction of RNA from the inactivated sample. Principles of Examination This procedure involves extraction of COVID-19 RNA from inactivated virus samples that have been aliquoted into plates. This protocol follows a method developed in-house that is automated on the Biomek FX liquid handling platform. All reagents and buffers prepared in house are batch tested and certified.

Published
2020

11. Automated transfer of inactivated virus samples from individual 2ml tubes to 96-well plate v1

Author

Efthymios Fidanis, Sophia Ward, Laura Cubitt, Amelia Edwards, Debbie Hughes, Michael Hubank, and Jerome Nicod

Subjects
Chromatography, Materials science, 96 well plate, Virus
Abstract

Purpose of examination / Clinical relevance At the end of 2019, several pneumonia cases were reported in Wuhan, China and the pathogen was confirmed as a new viral strain. World Health organization has named the newly identified coronavirus as 2019-nCoV, also known as SARS-Cov-2. The disease developed into a dangerous pandemic, posing major challenges to the NHS. Although more research is necessary to better understand the virus, in response to the emergency, simple and rapid testing is essential to identify the virus in infected individuals. This will aid the implementation of efficient interventions to contain the spread, and distinguish healthcare workers who have been infected, and are required to self-isolate, from those showing similar symptoms but which are not 2019-nCoV associated. The latter category may continue to work, alleviating stress on hard-pressed healthcare resources. 2019-nCoV is an RNA virus, and the diagnostic tests detect viral RNA in swabs from patient airways using a reverse transcriptase PCR assay. Samples are submitted to HSL, an accredited reporting laboratory, and transferred to the Crick for testing. The first step of the process is sample receipt at the Crick. This SOP describes the transfer of inactivated virus into plates for RNA extraction. Principles of Examination The assay uses the Hamilton robot to transfer 150 μl of 93 samples of inactivated viral media samples from Barcoded 2 ml tubes (Cat no. 72.694.005) to Barcoded 96 well Nunc plates (Cat no. 260251) maintaining sample identity. -- The authors wish to thank Heather Ringrose for support with the Hamilton liquid handlingworkstation.

Published
2020

12. Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas

Author

Julian Little, Harry Campbell, Christine Nyiraneza, Monica M. Bertagnolli, Zahra Montazeri, Luis G. Carvajal-Carmona, Ian Tomlinson, Victoria Svinti, Susan M. Farrington, Ann G. Zauber, Gillian Gresham, Malcolm G. Dunlop, Shanya Sivakumaran, Laura Cubitt, Evropi Theodoratou, Wanjing Chen, and Maria Timofeeva

Subjects
Adenoma, 0301 basic medicine, Gerontology, medicine.medical_specialty, Arylamine N-Acetyltransferase, Epidemiology, NAD(P)H Dehydrogenase, Library science, Genome-wide association study, Population health, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Methylenetetrahydrofolate Reductase, Risk Factors, NAD(P)H Dehydrogenase (Quinone), medicine, Humans, Genetic Predisposition to Disease, Polymorphism, Alleles, Methylenetetrahydrofolate Reductase (NADPH2), Preventive healthcare, business.industry, Public health, Statistics, Bayes Theorem, Single Nucleotide, General Medicine, Human genetics, Isoenzymes, 030104 developmental biology, 030220 oncology & carcinogenesis, Public Health and Health Services, Tumor Suppressor Protein p53, Biostatistics, Colorectal Neoplasms, business, Genome-Wide Association Study, Biomedical sciences
Abstract

Int. J. Epidemiol. Advance Access published October 7, 2015 International Journal of Epidemiology, 2015, 1–20 doi: 10.1093/ije/dyv185 Original article Original article Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas Downloaded from http://ije.oxfordjournals.org/ at Serials RecordsSerials on October 14, 2015 Zahra Montazeri, 1† Evropi Theodoratou, 2† Christine Nyiraneza, 1 Maria Timofeeva, 3 Wanjing Chen, 2 Victoria Svinti, 3 Shanya Sivakumaran, 2 Gillian Gresham, 1 Laura Cubitt, 2 Luis Carvajal-Carmona, 4 Monica M. Bertagnolli, 5 Ann G. Zauber, 6 Ian Tomlinson, 7 Susan M. Farrington, 3 Malcolm G. Dunlop, 3 Harry Campbell 2,3 and Julian Little 1 * School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada, 2 Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK, 3 Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK Biochemistry and Molecular Medicine, Genome and Biomedical Sciences Facility, UC Davis School of Medicine, University of California Davis, Davis, CA, USA, 5 Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA 6 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and 7 Wellcome Trust Centre for Human Genetics, Oxford, UK *Corresponding author. School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Canada. E-mail: jlittle@uottawa.ca Joint first authors. Accepted 20 August 2015 Abstract Background: Low penetrance genetic variants, primarily single nucleotide polymorph- isms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/]. Methods: We performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations. Results: We considered the association with the rs6983267 variant at 8q24 as ‘highly cred- ible’, reaching genome-wide statistical significance in at least one meta-analysis model. We identified ‘less credible’ associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V C The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association V

Published
2015

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