Accès ouvert déclaré2024article
Accelerated immune ageing is associated with COVID-19 disease severity
Janet M. Lord, Tonny Veenith, Jack Sullivan, Archana Sharma‐Oates, Alex Richter, Neil Greening, Hamish McAuley, Rachael A Evans, Paul Moss, Shona C. Moore, Lance Turtle, Nandan Gautam, Ahmed Gilani, Manan Bajaj, Louise V. Wain, Christopher E. Brightling, Betty Raman, Michael Marks, Amisha Singapuri, Omer Elneima, Peter Openshaw, Niharika A. Duggal, Kathryn M. Abel, Huzaifa Adamali, Davies Adeloye, O Adeyemi, R Adrego, L Aguilar-Jimenez, Sohail Ahmad, Nafees Haider, Rizwan Ahmed, N Ahwireng, Mark Ainsworth, B Al-Sheklly, A Alamoudi, Mohammad Ali, M Aljaroof, A.M. All, Louise Allan, Richard J. Allen, L. Allerton, Lynne Allsop, P. Almeida, Doris Altmann, Maria Alvarez Corral, S Amoils, Debra Anderson, Chrystalina A. Antoniades, Ana Arias, Chérie Armour, Lará Armstrong, Natalie Armstrong, David Arnold, H Arnold, Abdul Ashish, Andrew Ashworth, Mark Ashworth, S Aslani, H Assefa-Kebede, Catherine Atkin, Philip A. Atkin, Raminder Aul, Htin Aung, Luke Austin, Cristina Avram, A Ayoub, Marta Babores, Rob Baggott, J. Bagshaw, David Baguley, L. Charles Bailey, J. Kenneth Baillie, S. Bain, M Bakali, M Bakau, Eileen Baldry, David Baldwin, Molly M Baldwin, Clive Ballard, Amitava Banerjee, B. Bang, Ruth E Barker, L Barman, Shaney Barratt, Fiona Barrett, D Basire, N Basu, M. Bates, Andrew Bates, Rachel L. Batterham, Helen Baxendale, Hannah Bayes, Michael Beadsworth, P Beckett, M. Beggs, M Begum, Paul Beirne, D Bell, Robert M. Bell, Katherine Bennett, Eva Beranová, Areti Bermperi, A Berridge, Colin Berry, Sarah Betts, Emily Bevan, Kam Bhui, M Bingham, K Birchall, Lisa Bishop, Karen Bisnauthsing, J Blaikely, Angela Bloss, A Bolger, Charlotte E. Bolton, James Bonnington, A Botkai, C Bourne, Michelle Bourne, Kate Bramham, L Brear, Gerome Breen, J Breeze, Andrew Briggs, E Bright, Simon Brill, Khara Croswaite Brindle, L. Broad, A Broadley, C Brookes, Matthew R. Broome, A. Brown, Jeremy Brown, Mike Brown, Victoria Tzortziou Brown, Traolach Brugha, Nigel J. Brunskill, Maya H Buch, Philip Buckley, Anda Bularga, Edward T. Bullmore, L. Burden, Teresa Burdett, D Burn, Graham Burns, Angus C. Burns, John Busby, R. Butcher, Adeel A. Butt, Suzanne Byrne, Paula Cairns, Philip C. Calder, E Calvelo, H Carborn, Brittany Card, Christine Carr, L. Carr, Gail Carson, P. Carter, Anna Casey, Mark Philip Cassar, Jorunn Pauline Cavanagh, Manish Chablani, Trudie Chalder, James D. Chalmers, R C Chambers, Francis K.L. Chan, Keith M. Channon, K Chapman, A Charalambou, Nazia Chaudhuri, Anna M. Checkley, J. Chen, Yu Cheng, L Chetham, C Childs, Edwin R. Chilvers, Hector Chinoy, Amedeo Chiribiri, K Chong-James, Gourab Choudhury, Noura J. Choudhury, Phil Chowienczyk, C D C Christie, M Chrystal, Diane Clark, Collin M. Clark, Jennifer Clarke, Sara Clohisey, Gillian Coakley, Z Coburn, S Coetzee, Jennifer E. Cole, Christopher M. Coleman, F Conneh, David Connell, Bronwen Connolly, L Connor, A Cook, Brendan Cooper, D. James Cooper, Sheldon C. Cooper, Debra Copeland, Tracey Cosier, M Coulding, C Coupland, Eline G. M. Cox, Tom Craig, Philippe Crisp, D Cristiano, Michael G. Crooks, Adam Cross, I Cruz, Paul Cullinan, Daniel J. Cuthbertson, Luke Daines, M Dalton, Patricia Daly, A Daniels, Paul Dark, J Dasgin, Abel P. David, Elin Haf Davies, Ffyon Davies, Gwyneth A. Davies, Katherine Davies, Matthew Davies, Jennifer Dawson, E Daynes, Anthony De Soyza, B Deakin, Andrew Deans, C Deas, J Deery, Sylviane Defres, Amanda Dell, K Dempsey, Emma Denneny, John Dennis, Amy Dewar, R Dharmagunawardena, N Diar-Bakerly, Chris Dickens, A Dipper, Sarah Diver, S N Diwanji, Michael J. Dixon, Ratko Djukanović, Hannah Dobson, Stephen L. Dobson, Annemarie B Docherty, A Donaldson, Tao Dong, Natalie Dormand, Andrew Dougherty, Rowan Dowling, S Drain, K Draxlbauer, K. Drury, P Dulawan, A Dunleavy, S Dunn, C. Dupont, J Earley, Nicholas Easom, Carlos Echevarria, Sarah Edwards, Charlotte L. Edwardson, H El-Taweel, Angela Elliott, Katharine Elliott, Y Ellis, A Elmer, D Evans, Helen Evans, Jonathan Evans, Ray Evans, Teriann Evans, C Evenden, Lynsey Evison, Laura Fabbri, Sara Fairbairn, Andrea D. Fairman, K Fallon, David Faluyi, C Favager, T Fayzan, J. Featherstone, Tim Felton, J Finch, Simon J. Finney, J Finnigan, Lucy Finnigan, Helen L. Fisher, Simon Fletcher, R Flockton, M. G. Flynn, H Foot, David Foote, James D. Ford, Daniel Forton, E Fraile, C Francis, Rebecca Francis, Sarah Francis, Adam Frankel, Emily Fraser, Robert C. Free, Nigel French, Xiaotong Fu, Jonathan Fuld, James Furniss, L. Garner, J R Geddes, P M George, Michael Gibbons, Michael Gill, L Gilmour, Fergus Gleeson, J Glossop, S. W. Glover, Nigel Goodman, C Goodwin, Bibek Gooptu, Howard S. Gordon, T Gorsuch, M Greatorex, Paul L. Greenhaff, William Greenhalf, A Greenhalgh, John P. Greenwood, H Gregory, R. Gregory, D Grieve, Denise Griffin, Lori Griffiths, A-M Guerdette, Mahitha Gummadi, Ayush Gupta, Sambasivarao Gurram, Elspeth Guthrie, Z Guy, Henri Henson, Kate Hadley, A Haggar, Kirsten Hainey, Brigid Hairsine, Pranabashis Haldar, Ian P. Hall, L Hall, Mark Halling‐Brown, R Hamil, A Hancock, Kerry Hancock, Neil A. Hanley, Sulaimaan Haq, Hayley Hardwick, E. Hardy, T Hardy, Beverley Hargadon, Kevin J. Harrington, Emma Harris, V. C. Harris, Ewen M. Harrison, Phillippa Harrison, Nicholas Hart, A Harvey, M Harvey, M Harvie, Lynn Haslam‐Larmer, May Havinden-Williams, Jason E. Hawkes, N Hawkings, J Haworth, Adrian Hayday, M Haynes, Jon Hazeldine, T Hazelton, Liam G. Heaney, Cheryl Heeley, Jonathan L. Heeney, Melissa Heightman, Simon Heller, Morag Henderson, L Hesselden, Melissa Hewitt, V Highett, Toby Hillman, T Hiwot, Ling‐Pei Ho, A Hoare, M Hoare, J Hockridge, P Hogarth, A Holbourn, Sara Holden, Luke Holdsworth, D Holgate, M Holland, L Holloway, K. Holmes, Manisha Holmes, B Holroyd-Hind, L Holt, Anil Hormis, Alex Horsley, Akram A. Hosseini, Matthew Hotopf, Linzy Houchen‐Wolloff, Kenneth A. Howard, Luke Howard, Alice Howell, E Hufton, Alun D. Hughes, Joel W. Hughes, R Hughes, A Humphries, Nathan T. M. Huneke, E Hurditch, John R. Hurst, Masud Husain, Tracy Hussell, J Hutchinson, Wadah Ibrahim, F Ilyas, J Ingham, L Ingram, D Ionita, K Isaacs, Khalida Ismail, Thomas Jackson, Joseph Jacob, W Y James, Wooyoung Jang, C Jarman, Ian Jarrold, Hannah Jarvis, R Jastrub, B Jayaraman, Gísli Jenkins, Peter Jezzard, K Jiwa, Candace Johnson, SR Johnson, D Johnston, Caroline J. Jolley, D Jones, Graeme Jones, Ian A. Jones, L Jones, Mark G. Jones, Siana Jones, Sharon Jose, T Kabir, Georgios Kaltsakas, Vicky Kamwa, N. Kanellakis, S Kaprowska, Zunaira Kausar, Natalie Keenan, Sadie Kelly, Graham J. Kemp, S Kerr, Helen Kerslake, A L Key, Fasihul Khan, Kamlesh Khunti, Susan Kilroy, B. King, C King, L. Kingham, Jodie Kirk, Pádraig T. Kitterick, Paul Klenerman, Lucy Knibbs, Stella C. Knight, A. Knighton, Onn Min Kon, Samantha S.C. Kon, S. Koprowska, Ania Korszun, Ivan Koychev, C Kurasz, P Kurupati, Charles Laing, H. Lamlum, G Landers, Claudia Langenberg, Daniel Lasserson, Lara Lavelle-Langham, Alison M. Lawrie, Claire Lawson, A Layton, A Lea, Olivia C. Leavy, D. Lee, J.-H. Lee, E. Lee, K. Leitch, R Lenagh, Daniel J. Lewis, James E. M. Lewis, Keir Lewis, Virginia Lewis, N Lewis-Burke, X. Li, Teresa Light, Liz Lightstone, W. Lilaonitkul, L. Lim, S Linford, Anne Lingford‐Hughes, Marc Lipman, Kamal Liyanage, Adam Lloyd, Sarah Logan, David A. Lomas, Nazir Lone, Ronda Loosley, Harpreet Lota, Wayne Lovegrove, Alice Lucey, Elena Lukaschuk, A Lye, C. Lynch, Steven MacDonald, Guy MacGowan, Irene Macharia, J Mackie, L Macliver, S Madathil, G Madzamba, N Magee, M M Magtoto, N Mairs, Nauman Majeed, Eugene O. Major, Flora Malein, Michael H. Malim, Georgia Mallison, William D‐C Man, Sema Mandal, Kenneth Mangion, Charlotte Manisty, R Manley, Keith L. March, Stefan J. Marciniak, Pietro Marino, M Mariveles, E Marouzet, S. Marsh, Ben G. Marshall, Michael S. Marshall, James Martín, Adrian R. Martineau, Luis M. Martínez, Nick Maskell, Darwin Matila, Wadzanai Matimba-Mupaya, Lauren Matthews, A Mbuyisa, Stephen P. McAdoo, R. Hamish McAllister‐Williams, Angela McArdle, P McArdle, D McAulay, Gerry P McCann, Jacqueline McCormick, W McCormick, P McCourt, Lorcan McGarvey, C. A. McGhee, Kirsty McGee, J McGinness, K McGlynn, A McGovern, Heather McGuinness, Iain B. McInnes, J McIntosh, E McIvor, K McIvor, L McLeavey, Anne McMahon, Michael McMahon, Liam McMorrow, T Mcnally, Melitta A. McNarry, J McNeill, Alison McQueen, H McShane, C Mears, C Megson, S Megson, Puja Mehta, James Meiring, L Melling, Mark Mencias, Dan Menzies, Marta Merida Morillas, A. Michael, Chris Miller, Lea Milligan, C Mills, Gary Mills, Nicholas L. Mills, L Milner, Shivani Misra, Jane A. Mitchell, A. Mohamed, N Mohamed, Sarhan Mohammed, Philip L. Molyneaux, W Monteiro, S Moriera, Anna Morley, Leigh Morrison, Richard Morriss, A Morrow, Alastair J. Moss, K Motohashi, N Msimanga, Elizabeta B. Mukaetova‐Ladinska, U Munawar, Jennifer Murira, Uttam Nanda, H Nassa, M Nasseri, A Neal, R. Needham, P Neill, Stefan Neubauer, David E. Newby, Helen Newell, Tom Newman, Julia Newman, A. Newton-Cox, Timothy R. Nicholson, D Nicoll, A. Nikolaidis, Claire M. Nolan, Michael Noonan, Chris Norman, Petr Novotný, J Nunag, Lorenza Nwafor, U Nwanguma, J Nyaboko, Conor O’Brien, Kieran J. O’Donnell, D. O’Regan, L O'Brien, N Odell, Graham S. Ogg, O Olaosebikan, C Oliver, Z Omar, L. Orriss-Dib, Lynn Osborne, R Osbourne, Marlies Ostermann, Christopher E. Overton, J. Owen, J Oxton, Jamie Pack, Edmund Pacpaco, Stella‐Maria Paddick, S Painter, Ashkan Pakzad, S. Palmer, Padmasayee Papineni, Kitty Paques, Kerry Paradowski, Manish Pareek, Dhruv Parekh, Helen Parfrey, Carmine M. Pariante, Sean Parker, J. Parmar, S Patale, B. Patel, Manishkumar Patel, Suhani Patel, D Pattenadk, M Pavlides, Sarah Payne, Lyndsay Pearce, John E. Pearl, D. Peckham, Jessica Pendlebury, Yanchun Peng, Catherine Pennington, I Peralta, Emma Perkins, Zhane Peterkin, Tim Peto, Nayia Petousi, Jennifer Petrie, Paul Pfeffer, J Phipps, J Pimm, Karen Piper Hanley, Riinu Pius, H Plant, Sven Plein, Tatiana Plekhanova, Megan Plowright, O Polgar, Lonneke van de Poll, Joanna C. Porter, S Portukhay, Nick Powell, A Prabhu, John Pratt, Angeline Price, David A. Price, L Price, A Prickett, J. Propescu, S. Prosper, S. Pugmire, Sheena Quaid, J Quigley, Jennifer K Quint, H Qureshi, Imran Nazir Qureshi, Kavita Radhakrishnan, Najib M. Rahman, Markus Ralser, A. Ramos, H. Ramos, J Rangeley, B Rangelov, L Ratcliffe, P Ravencroft, A Reddington, Raghunath Reddy, A. Vijaya Bhaskar Reddy, H Redfearn, Dawn Redwood, Anna Reed, Megan Rees, T Rees, Karen Regan, Will Reynolds, Cinthia Mucci Ribeiro, A Richards, E Richardson, Matthew Richardson, Pilar Rivera‐Ortega, K. Roberts, Elaine Robertson, Emma C. Robinson, Lisa A. Robinson, L Roche, Chloe Roddis, J. Rodger, Amelia Ross, G Ross, J Rossdale, Anthony Rostron, Anna Rowe, J Rowland, Matthew Rowland, Sarah Rowland‐Jones, Krishna Chandra Roy, Maxim Roy, Igor Rudan, Richard Russell, Emma Russell, G Saalmink, R. Sabit, Elizabeth K. Sage, T Samakomva, N Samani, Claire Sampson, Katie Samuel, R Samuel, Amanda Sanderson, Elizabeth Sapey, Dinesh Saralaya, Jack Sargent, C Sarginson, Thea Sass, Naveed Sattar, Karen Saunders, Richard M. Saunders, Peter Saunders, L. C. Saunders, Heather Savill, W Saxon, Avan Aihie Sayer, J Schronce, Wilhelm Schwaeble, J. T. Scott, K Scott, Nicholas M. Selby, Malcolm G. Semple, Marco Sereno, T Sewell, Ajay M. Shah, Kanan Shah, Pallav L. Shah, Manu Shankar‐Hari, Manish Sharma, Claire C. Sharpe, Michael Sharpe, S Shashaa, Andrew Shaw, Kaitlin Shaw, Victoria Shaw, Aziz Sheikh, Sarah Shelton, L Shenton, K Shevket, A Shikotra, Jay M. Short, S Siddique, Salman Siddiqui, J Sidebottom, Louise Sigfrid, G Simons, Jennifer Simpson, Nicholas Simpson, Claire Singh, Suveer Singh, Sally Singh, D Sissons, J Skeemer, Katie Slack, Andrew Smith, Davey M. Smith, Susan M. Smith, John A. Smith, Lauren C. Smith, M Soares, T S Solano, Reanne Solly, A R Solstice, T Soulsby, David Southern, D. Sowter, Mark Spears, L. G. Spencer, F Speranza, Louise Stadon, Stefan Stanel, N Steele, Michael Steiner, David J. Stensel, G Stephens, L Stephenson, M. Stern, Iain Stewart, R Stimpson, Skye Stockdale, James Stockley, William Thornley Stoker, Richard Stone, W Storrar, A. Storrie, Kim Storton, Jeffrey S. A. Stringer, Sophia Strong-Sheldrake, Natalie Stroud, Christian P Subbe, Cathie Sudlow, Z Suleiman, Charlotte Summers, Christina Summersgill, D Sutherland, Dominic L. Sykes, Robert Sykes, Nick P. Talbot, Ai Lyn Tan, L Tarusan, Vera Tavoukjian, Alex H. Taylor, C Taylor, J Taylor, A Te, H Tedd, C J Tee, J Teixeira, Helen Tench, S. Terry, S. Thackray-Nocera, Favas Thaivalappil, B Thamu, David Thickett, C Thomas, David Thomas, S Thomas, Abey Thomas, T Thomas-Woods, T Thompson, A. A. Roger Thompson, T Thornton, Mathew Thorpe, Ryan S. Thwaites, J Tilley, N Tinker, Gerlynn Tiongson, Martin D. Tobin, James Tomlinson, Catherine Tong, Mark Toshner, Rhian M. Touyz, K A Tripp, Elizabeth M. Tunnicliffe, Alison E. Turnbull, Emma L. Turner, Steve Turner, Victoria Turner, K. Turner, Sharon Turney, H. Turton, J Ugoji, R Ugwuoke, Rachel Upthegrove, Jonathan Valabhji, Maria Teresa Ventura, Joanne Vere, Carinna Vickers, B Vinson, Erin A. Wade, Phillip Wade, Thomas W. Wainwright, L O Wajero, S Walder, Emma Wall, T Wallis, Sharon Walmsley, Jessica A. Walsh, Simon Walsh, L Warburton, Tom Ward, K Warwick, Helen Wassall, Sharon Waterson, Eleanor Watson, Lea C. Watson, Judith Watson, Carly Welch, H Welch, B Welsh, Simon Wessely, S West, H Weston, Helen Wheeler, Simon R. White, Victor Whitehead, Julie Whitney, Spence Whittaker, B. Whittam, V Whitworth, Andrew Wight, Jim M. Wild, Martin R. Wilkins, Dean Wilkinson, Bryan Williams, Nefyn Williams, J. E. Williams, S A Williams-Howard, Michelle Willicombe, Guillermo B. Willis, J Willoughby, A Wilson, David M. Wilson, Iseult Wilson, Nicola Window, Miles D. Witham, R Wolf-Roberts, C Wood, Felix Woodhead, Jeffrey A. Woods, Dan Wootton, Joanne Wormleighton, J Worsley, David C. Wraith, C Wrey Brown, Clinton B. Wright, L Wright, S. Wright, J Wyles, Inez Wynter, Mengxin Xu, N Yasmin, S Yasmin, Thomas Yates, Kay Por Yip, Bernadette Young, Scott Young, Alison L. Young, Ahmed Yousuf, A. Zawia, Lisa Zeidan, Bo Zhao, Bang Zheng, O Zongo
30Citations signalées
16Institutions associées
1Pays d’affiliation
Résumé fourni par la source
Abstract Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe ( n = 56; age 53.12 ± 11.30 years), moderate ( n = 32; age 52.28 ± 11.43 years) or mild ( n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults ( n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells ( p < 0.0001); increased frequency of EMRA CD4 ( p < 0.003) and CD8 T cells ( p < 0.001); a higher frequency ( p < 0.0001) and absolute numbers ( p < 0.001) of CD28 −ve CD57 +ve senescent CD4 and CD8 T cells; higher frequency ( p < 0.003) and absolute numbers ( p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation ( p < 0.0001); higher frequency of memory B cells ( p < 0.001) and increased frequency ( p < 0.0001) and numbers ( p < 0.001) of CD57 +ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls ( p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( $$\beta$$ β = 0.174, p = 0.043), with a major influence being disease severity ( $$\beta$$ β = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.
Sujets associés
COVID-19 Clinical Research StudiesLong-Term Effects of COVID-19Immune responses and vaccinations