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3 results on '"Kelvin Hunter"'

1. Delayed bystander CD8 T cell activation, early immune pathology and persistent dysregulation characterise severe COVID-19

Author

Caroline Saunders, Jeremy K. Nicholson, Nathalie Kingston, Lorinda Turner, John Bradley, Ian Goodfellow, Erik J M Toonen, Anne Elmer, Michael D Morgan, Michael P. Weekes, Berthold Göttgens, Paul A. Lyons, Paul J. Lehner, Aloka DeSa, Oisin Huhn, Myra Hosmillo, Kelvin Hunter, Nicholas J Matheson, Prasanti Kotagiri, Christoph Hess, James Thaventhiran, Pehuen Pereyra Gerber, Laura Bergamaschi, Anna M. Petrunkina, Ravindra K. Gupta, Benjamin J. Dunmore, Gordon Dougan, Aimee Hanson, Mark R. Wills, Kenneth G. C. Smith, Hélène Ruffieux, Sylvia Richardson, Federica Mescia, Fernando Calero Nieto, Rainer Doffinger, Stephen Baker, Mark Toshner, and CambridgeInstituteofTherapeuticImmunologyandInfectiousDisease-NationalInstituteofHealthResearch(CITI)

Subjects
Immune system, business.industry, Immunopathology, Immunology, medicine, Bystander effect, Inflammation, Tumor necrosis factor alpha, medicine.symptom, Systemic inflammation, business, Asymptomatic, Viral load
Abstract

SummaryIn a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust bystander CD8 T cell immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed bystander responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune defects may have clinical implications.

Published
2021

2. Author response: Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Author

Jennifer Webster, Stephen Baker, Neil Bartholomew, Aminu S Jahun, Rutendo Nyagumbo, Mark Toshner, Julie Harris, Paul J. Lehner, Charlotte J. Houldcroft, Lisa Thake, Sarah L Caddy, Benjamin J. Dunmore, Afzal N. Chaudhry, Theresa Feltwell, Christian Sparke, M. Estée Török, Nick K Jones, Michael P. Weekes, Emma Le Gresley, Simon McCallum, Tim Raine, Josefin Bartholdson Scott, Grant Hall, Myra Hosmillo, Stewart Fuller, Andrew Hinch, Angela Wright, Gordon Dougan, Jane Rowlands, Aileen Narcorda, Sally Forrest, Claire Cormie, Jennifer M. Martin, Kathleen E Stirrups, Sarah Hewitt, Natalie Quinnell, Joy Shih, Katie Dempsey, Geraldine Martell, Helen Murphy, Ashley Shaw, Cherry Publico, Heather F Jones, Carmen M. Treacy, Anne-Laure Vallier, Surendra Parmar, Jennifer Wood, Ariana Betancourt, Ashlea Bucke, Debbie Read, Helen Butcher, Martin D. Curran, Penelope-Jane Eames, Sushmita Sridhar, Chris McNicholas, Dominic Sparkes, Ian Goodfellow, Nicola Reynolds, Ciara O’Donnell, Valentina Ruffolo, Jane Kennet, Fahad A Khokhar, Hannah Stark, Paul A. Lyons, Francescsa Nice, Karen Brookes, Lenette Mactavous, Claire Mather, Maddie Epping, Aloka De Sa, Lucy Warboys, Isabel Cruz, Naidine Escoffery, Carla Ribeiro, Ailsa Bowring, Nicholas J Matheson, Iain Kean, Tobias Tilly, Daniel Lewis, Ravi Gupta, Kelvin Hunter, Giles Wright, Anne Roberts, Hugo Tordesillas, Isobel Jarvis, Nicholas K. Brown, Laura Bergamaschi, Anne Elmer, Harmeet Gill, Oisin Huhn, D. Johnson, Laura G Caller, John Bradley, Caroline Saunders, Federica Mescia, Joanna Calder, Anna Yakovleva, Jo Price, Richard J. Samworth, Kenneth G. C. Smith, Mary Kasanicki, Hongyi Zhang, Laura Canna, Rebecca Rastall, Jo Wright, Ben Warne, Simone Hargreaves, Anita Furlong, Josh Hodgson, Daniela Caputo, Stefan Gräf, Jamie Young, Sofia Papadia, Criona O Brien, Kirsty Lagadu, Georgie Bowyer, Michelle Wantoch, Ekaterina Legchenko, Debra Clapham-Riley, Rachel Sutcliffe, Joe Marsden, Mark Ferris, Tim Gould, Mailis Maes, Luke W. Meredith, Joana Pereira-Dias, Nicola Ramenatte, Matthew Routledge, Nathalie Kingston, Helen Dolling, William L Hamilton, Linda Pointon, Christopher Huang, Barbara J. Graves, Lucy Rivett, Anne Meadows, and Zhen Tong

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Asymptomatic, law.invention, Carriage, Transmission (mechanics), law, Health care, medicine, medicine.symptom, Intensive care medicine, business
Published
2020

3. Early Immune Pathology and Persistent Dysregulation Characterise Severe COVID-19

Author

Laura Bergamaschi, Federica Mescia, Lorinda Turner, Aimee Hanson, Prasanti Kotagiri, Benjamin J. Dunmore, Helene Ruffieux, Aloka De Sa, Oisin Huhn, Mark R. Wills, Stephen Baker, Rainer Doffinger, Gordon Dougan, Anne Elmer, Ian Goodfellow, Ravindra K. Gupta, Myra Hosmillo, Kelvin Hunter, Nathalie Kingston, Paul Lehner, Nicholas J. Matheson, Jeremy K. Nicholson, Anna M. Petrunkina, Sylvia Richardson, Caroline Saunders, James Thaventhiran, Erik J. M. Toonen, Michael P. Weekes, (CITIID-NIHR) COVID BioResource Col Group, Mark Toshner, Christoph Hess, John R. Bradley, Paul A. Lyons, and Kenneth G.C. Smith

Subjects
medicine.medical_specialty, business.industry, Inflammation, Systemic inflammation, Asymptomatic, Clinical research, Immune system, Internal medicine, Immunopathology, Medicine, Tumor necrosis factor alpha, medicine.symptom, business, Viral load
Abstract

In a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to “long COVID”. Funding: We are grateful for the generous support of CVC Capital Partners, the Evelyn Trust (20/75), UKRI COVID Immunology Consortium, Addenbrooke’s Charitable Trust (12/20A) and the NIHR Cambridge Biomedical Research Centre for their financial support. K.G.C.S. is the recipient of a Wellcome Investigator Award (200871/Z/16/Z); M.P.W. is the recipient of Wellcome Senior Clinical Research Fellowship (108070/Z/15/Z); C.H. was funded by a Wellcome COVID-19 Rapid Response DCF and the Fondation Botnar; N.M. was funded by the MRC (CSF MR/P008801/1) and NHSBT (WPA15-02); I.G.G. is a Wellcome Senior Fellow and was supported by funding from the Wellcome (Ref: 207498/Z/17/Z). Conflict of Interest: The authors declare they have no competing interests.

Published
2020

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