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7 results on '"Lenette Mactavous"'

1. Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID

Author

Benjamin A. Krishna, Eleanor Y. Lim, Lenette Mactavous, Paul A. Lyons, Rainer Doffinger, John R. Bradley, Kenneth G.C. Smith, John Sinclair, Nicholas J. Matheson, Paul J. Lehner, Mark R. Wills, and Nyaradzai Sithole

Subjects
Long COVID, T cell, Assay, SARS-CoV-2, Immunity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative. Methods: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients. Findings: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/−13%) and specific (88%+/−7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42–53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses. Interpretation: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID. Funding: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).

Published
2022
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2. Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID

Author

Benjamin Krishna, Eleanor Lim, Lenette Mactavous, Sarah Jackson, NIHR BioResource Team NIHR BioResource Team, Paul Lyons, Rainer Doffinger, John Bradley, Kenneth Smith, John Sinclair, Nicholas Matheson, Paul Lehner, Nyaradzai Sithole, and Mark Wills

Abstract

After acute infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a significant proportion (0.2 – 30%) of patients experience persistent symptoms beyond 12 weeks, termed Long COVID. Understanding the mechanisms which cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic and monitoring purposes is urgently required. Persistently high levels of IFN-γ were detected from peripheral blood mononuclear cells (PBMCs) of Long COVID patients using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in Long Covid patients, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. IFN-γ release was CD8+ T cell mediated and dependent on MHC-I antigen presentation by CD14+ cells. After vaccination, a significant decrease in IFN-γ correlated with resolution of some Long COVID symptoms. Our study highlights a key mechanism underlying Long COVID, enabling the search for biomarkers and therapeutics in patients with Long COVID.

Published
2022

3. Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID

Author

Benjamin A. Krishna, Eleanor Y. Lim, Lenette Mactavous, Sarah Jackson, NIHR BioResource Team, Paul A. Lyons, Rainer Doffinger, John R. Bradley, Kenneth G. C. Smith, John Sinclair, Nicholas J. Matheson, Paul J. Lehner, Nyaradzai Sithole, and Mark R. Wills

Abstract

After acute infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a significant proportion (0.2–30%) of patients experience persistent symptoms beyond 12 weeks, termed Long COVID. Understanding the mechanisms which cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic and monitoring purposes is urgently required. Persistently high levels of IFN-γ were detected from peripheral blood mononuclear cells (PBMCs) of Long COVID patients using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in Long Covid patients, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. IFN-γ release was CD8+ T cell mediated and dependent on MHC-I antigen presentation by CD14+ cells. After vaccination, a significant decrease in IFN-γ correlated with resolution of some Long COVID symptoms. Our study highlights a key mechanism underlying Long COVID, enabling the search for biomarkers and therapeutics in patients with Long COVID.

Published
2022

4. Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID

Author

Benjamin A. Krishna, Eleanor Y. Lim, Lenette Mactavous, Paul A. Lyons, Rainer Doffinger, John R. Bradley, Kenneth G.C. Smith, John Sinclair, Nicholas J. Matheson, Paul J. Lehner, Mark R. Wills, and Nyaradzai Sithole

Subjects
Post-Acute COVID-19 Syndrome, SARS-CoV-2, COVID-19, Humans, Interleukin-2, General Medicine, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology
Abstract

There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative.Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients.We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses.Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID.This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).

Published
2021

5. Retrospective diagnosis of SARS-CoV-2 infection in patients with Long COVID by measuring specific T cell mediated IL-2 release

Author

Benjamin A. Krishna, Eleanor Y. Lim, Lenette Mactavous, NIHR BioResource Team, Paul Lyons, Rainer Doffinger, John Bradley, Kenneth G. C. Smith, John Sinclair, Nicholas J. Matheson, Paul J. Lehner, Mark R. Wills, and Nyaradzai Sithole

Subjects
medicine.medical_specialty, Research ethics, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), T cell, Nice, Retrospective diagnosis, medicine.anatomical_structure, Internal medicine, Cohort, medicine, In patient, business, computer, computer.programming_language
Abstract

National Institute for Health and Care Excellence (NICE) guidelines define Long COVID as signs and symptoms that develop during or after an infection consistent with COVID-19, that continue for more than 12 weeks and are not explained by an alternative diagnosis. Long COVID is as yet poorly understood and difficult to diagnose. The diagnostic complexity of Long COVID is compounded in many patients who were infected with SARS-CoV-2 but not tested at acute presentation and are antibody negative. Given the diagnostic conundrum of Long COVID, we set out to design a SARS-CoV-2 specific T cell assay, to follow up a cohort of undifferentiated mostly non-hospitalised patients with Long COVID for up to 13 months. Here, we show that IL-2 release from SARS-CoV-2-specific memory T cells shows >75% sensitivity and >88% specificity in identifying individuals with confirmed SARS-CoV-2 infection >6 months after a positive PCR test.Funding: This work was funded by Addenbrooke’s Charitable Trust grant awarded to N.S. and supported by the NIHR Cambridge Biomedical Research Centre.Declaration of Interest: The authors declare no competing interestsEthical Approval: The Long COVID study patients were recruited and consented under the Cambridge COVID-19 NIHR BioResource joint Consent Form (Research Ethics Committee (NRES number (REC)) no. T1gC1) study NBR87.

Published
2021

6. Author response: Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Author

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

Subjects
medicine.medical_specialty, Transmission (mechanics), Coronavirus disease 2019 (COVID-19), business.industry, law, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Period (gene), Emergency medicine, Health care, Medicine, business, law.invention
Published
2020

7. 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

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