학술논문
Accelarated immune ageing is associated with COVID-19 disease severity
Document Type
Academic Journal
Author
Lord, Janet M.; Veenith, Tonny; Sullivan, Jack; Sharma-Oates, Archana; Richter, Alex G.; Greening, Neil J.; McAuley, Hamish J. C.; Evans, Rachael A.; Moss, Paul; Moore, Shona C.; Turtle, Lance; Gautam, Nandan; Gilani, Ahmed; Bajaj, Manan; Wain, Louise V.; Brightling, Christopher; Raman, Betty; Marks, Michael; Singapuri, Amisha; Elneima, Omer; Openshaw, Peter J. M.; Duggal, Niharika A.; Abel, K.; Adamali, H.; Adeloye, D.; Adeyemi, O.; Adrego, R.; AguilarJimenez, L. A.; Ahmad, S.; Ahmad Haider, N; Ahmed, R.; Ahwireng, N.; Ainsworth, M.; Al-Sheklly, B.; Alamoudi, A.; Ali, M.; Aljaroof, M.; All, A. M.; Allan, L.; Allen, R. J.; Allerton, L.; Allsop, L.; Almeida, P.; Altmann, D.; Alvarez Corral, M; Amoils, S.; Anderson, D.; Antoniades, C.; Arbane, G.; Arias, A.; Armour, C.; Armstrong, L.; Armstrong, N.; Arnold, D.; Arnold, H.; Ashish, A.; Ashworth, A.; Ashworth, M.; Aslani, S.; Assefa-Kebede, H.; Atkin, C.; Atkin, P.; Aul, R.; Aung, H.; Austin, L.; Avram, C.; Ayoub, A.; Babores, M.; Baggott, R.; Bagshaw, J.; Baguley, D.; Bailey, L.; Baillie, J. K.; Bain, S.; Bakali, M.; Bakau, M.; Baldry, E.; Baldwin, D.; Baldwin, M.; Ballard, C.; Banerjee, A.; Bang, B.; Barker, R. E.; Barman, L.; Barratt, S.; Barrett, F.; Basire, D.; Basu, N.; Bates, M.; Bates, A.; Batterham, R.; Baxendale, H.; Bayes, H.; Beadsworth, M.; Beckett, P.; Beggs, M.; Begum, M.; Beirne, P.; Bell, D.; Bell, R.; Bennett, K.; Beranova, E.; Bermperi, A.; Berridge, A.; Berry, C.; Betts, S.; Bevan, E.; Bhui, K.; Bingham, M.; Birchall, K.; Bishop, L.; Bisnauthsing, K.; Blaikely, J.; Bloss, A.; Bolger, A.; Bolton, C. E.; Bonnington, J.; Botkai, A.; Bourne, C.; Bourne, M.; Bramham, K.; Brear, L.; Breen, G.; Breeze, J.; Briggs, A.; Bright, E.; Brill, S.; Brindle, K.; Broad, L.; Broadley, A.; Brookes, C.; Broome, M.; Brown, A.; Brown, J.; Brown, J. S.; Brown, M.; Brown, V.; Brugha, T.; Brunskill, N.; Buch, M.; Buckley, P.; Bularga, A.; Bullmore, E.; Burden, L.; Burdett, T.; Burn, D.; Burns, G.; Burns, A.; Busby, J.; Butcher, R.; Butt, A.; Byrne, S.; Cairns, P.; Calder, P. C.; Calvelo, E.; Carborn, H.; Card, B.; Carr, C.; Carr, L.; Carson, G.; Carter, P.; Casey, A.; Cassar, M.; Cavanagh, J.; Chablani, M.; Chalder, T.; Chalmers, J. D.; CHambers, R. C.; Chan, F.; Channon, K. M.; Chapman, K.; Charalambou, A.; Chaudhuri, N.; Checkley, A.; Chen, J.; Cheng, Y.; Chetham, L.; Childs, C.; Chilvers, E. R.; Chinoy, H.; Chiribiri, A.; Chong-James, K.; Choudhury, G.; Choudhury, N.; Chowienczyk, P.; Christie, C.; Chrystal, M.; Clark, D.; Clark, C.; Clarke, J.; Clohisey, S.; Coakley, G.; Coburn, Z.; Coetzee, S.; Cole, J.; Coleman, C.; Conneh, F.; Connell, D.; Connolly, B.; Connor, L.; Cook, A.; Cooper, B.; Cooper, J.; Cooper, S.; Copeland, D.; Cosier, T.; Coulding, M.; Coupland, C.; Cox, E.; Craig, T.; Crisp, P.; Cristiano, D.; Crooks, M. G.; Cross, A.; Cruz, I.; Cullinan, P.; Cuthbertson, D.; Daines, L.; Dalton, M.; Daly, P.; Daniels, A.; Dark, P.; Dasgin, J.; David, A.; David, C.; Davies, E.; Davies, F.; Davies, G.; Davies, G. A.; Davies, K.; Davies, M. J.; Dawson, J.; Daynes, E.; De Soyza, A.; Deakin, B.; Deans, A.; Deas, C.; Deery, J.; Defres, S.; Dell, A.; Dempsey, K.; Denneny, E.; Dennis, J.; Dewar, A.; Dharmagunawardena, R.; Diar-Bakerly, N.; Dickens, C.; Dipper, A.; Diver, S.; Diwanji, S. N.; Dixon, M.; Djukanovic, R.; Dobson, H.; Dobson, S. L.; Docherty, A. B.; Donaldson, A.; Dong, T.; Dormand, N.; Dougherty, A.; Dowling, R.; Drain, S.; Draxlbauer, K.; Drury, K.; Dulawan, P.; Dunleavy, A.; Dunn, S.; Dupont, C.; Earley, J.; Easom, N.; Echevarria, C.; Edwards, S.; Edwardson, C.; El-Taweel, H.; Elliott, A.; Elliott, K.; Ellis, Y.; Elmer, A.; Evans, D.; Evans, H.; Evans, J.; Evans, R.; Evans, R. I.; Evans, T.; Evenden, C.; Evison, L.; Fabbri, L.; Fairbairn, S.; Fairman, A.; Fallon, K.; Faluyi, D.; Favager, C.; Fayzan, T.; Featherstone, J.; Felton, T.; Finch, J.; Finney, S.; Finnigan, J.; Finnigan, L.; Fisher, H.; Fletcher, S.; Flockton, R.; Flynn, M.; Foot, H.; Foote, D.; Ford, A.; Forton, D.; Fraile, E.; Francis, C.; Francis, R.; Francis, S.; Frankel, A.; Fraser, E.; Free, R.; French, N.; Fu, X.; Fuld, J.; Furniss, J.; Garner, L.; Geddes, J. R.; George, J.; George, P.; Gibbons, M.; Gill, M.; Gilmour, L.; Gleeson, F.; Glossop, J.; Glover, S.; Goodman, N.; Goodwin, C.; Gooptu, B.; Gordon, H.; Gorsuch, T.; Greatorex, M.; Greenhaff, P. L.; Greenhalf, W.; Greenhalgh, A.; Greenwood, J.; Gregory, H.; Gregory, R.; Grieve, D.; Griffin, D.; Griffiths, L.; Guerdette, A.-M.; Guillen Guio, B; Gummadi, M.; Gupta, A.; Gurram, S.; Guthrie, E.; Guy, Z.; Henson, H.; Hadley, K.; Haggar, A.; Hainey, K.; Hairsine, B.; Haldar, P.; Hall, I.; Hall, L.; Halling-Brown, M.; Hamil, R.; Hancock, A.; Hancock, K.; Hanley, N. A.; Haq, S.; Hardwick, H. E.; Hardy, E.; Hardy, T.; Hargadon, B.; Harrington, K.; Harris, E.; Harris, V. C.; Harrison, E. M.; Harrison, P.; Hart, N.; Harvey, A.; Harvey, M.; Harvie, M.; Haslam, L.; Havinden-Williams, M.; Hawkes, J.; Hawkings, N.; Haworth, J.; Hayday, A.; Haynes, M.; Hazeldine, J.; Hazelton, T.; Heaney, L. G.; Heeley, C.; Heeney, J. L.; Heightman, M.; Heller, S.; Henderson, M.; Hesselden, L.; Hewitt, M.; Highett, V.; Hillman, T.; Hiwot, T.; Ho, L. P.; Hoare, A.; Hoare, M.; Hockridge, J.; Hogarth, P.; Holbourn, A.; Holden, S.; Holdsworth, L.; Holgate, D.; Holland, M.; Holloway, L.; Holmes, K.; Holmes, M.; Holroyd-Hind, B.; Holt, L.; Hormis, A.; Horsley, A.; Hosseini, A.; Hotopf, M.; Houchen-Wolloff, L.; Howard, K.; Howard, L. S.; Howell, A.; Hufton, E.; Hughes, A. D.; Hughes, J.; Hughes, R.; Humphries, A.; Huneke, N.; Hurditch, E.; Hurst, J.; Husain, M.; Hussell, T.; Hutchinson, J.; Ibrahim, W.; Ilyas, F.; Ingham, J.; Ingram, L.; Ionita, D.; Isaacs, K.; Ismail, K.; Jackson, T.; Jacob, J.; James, W. Y.; Jang, W.; Jarman, C.; Jarrold, I.; Jarvis, H.; Jastrub, R.; Jayaraman, B.; Jenkins, R. G.; Jezzard, P.; Jiwa, K.; Johnson, C.; Johnson, S.; Johnston, D.; Jolley, C. J.; Jones, D.; Jones, G.; Jones, H.; Jones, I.; Jones, L.; Jones, M. G.; Jones, S.; Jose, S.; Kabir, T.; Kaltsakas, G.; Kamwa, V.; Kanellakis, N.; Kaprowska, S.; Kausar, Z.; Keenan, N.; Kelly, S.; Kemp, G.; Kerr, S.; Kerslake, H.; Key, A. L.; Khan, F.; Khunti, K.; Kilroy, S.; King, B.; King, C.; Kingham, L.; Kirk, J.; Kitterick, P.; Klenerman, P.; Knibbs, L.; Knight, S.; Knighton, A.; Kon, O.; Kon, S.; Kon, S. S.; Koprowska, S.; Korszun, A.; Koychev, I.; Kurasz, C.; Kurupati, P.; Laing, C.; Lamlum, H.; Landers, G.; Langenberg, C.; Lasserson, D.; Lavelle-Langham, L.; Lawrie, A.; Lawson, C.; Layton, A.; Lea, A.; Leavy, O. C.; Lee, D.; Lee, J.-H.; Lee, E.; Leitch, K.; Lenagh, R.; Lewis, D.; Lewis, J.; Lewis, K. E.; Lewis, V.; Lewis-Burke, N.; Li, X.; Light, T.; Lightstone, L.; Lilaonitkul, W.; Lim, L.; Linford, S.; Lingford-Hughes, A.; Lipman, M.; Liyanage, K.; Lloyd, A.; Logan, S.; Lomas, D.; Lone, N. I.; Loosley, R.; Lota, H.; Lovegrove, W.; Lucey, A.; Lukaschuk, E.; Lye, A.; Lynch, C.; MacDonald, S.; MacGowan, G.; Macharia, I.; Mackie, J.; Macliver, L.; Madathil, S.; Madzamba, G.; Magee, N.; Magtoto, M. M.; Mairs, N.; Majeed, N.; Major, E.; Malein, F.; Malim, M.; Mallison, G.; Man, W. D.-C.; Mandal, S.; Mangion, K.; Manisty, C.; Manley, R.; March, K.; Marciniak, S.; Marino, P.; Mariveles, M.; Marouzet, E.; Marsh, S.; Marshall, B.; Marshall, M.; Martin, J.; Martineau, A.; Martinez, L. M.; Maskell, N.; Matila, D.; Matimba-Mupaya, W.; Matthews, L.; Mbuyisa, A.; McAdoo, S.; McAllister-Williams, H.; McArdle, A.; McArdle, P.; McAulay, D.; McCann, G. P.; McCormick, J.; McCormick, W.; McCourt, P.; Mcgarvey, L.; McGhee, C.; Mcgee, K.; McGinness, J.; McGlynn, K.; McGovern, A.; McGuinness, H.; McInnes, I. B.; McIntosh, J.; McIvor, E.; McIvor, K.; McLeavey, L.; McMahon, A.; McMahon, M. J.; McMorrow, L.; Mcnally, T.; McNarry, M.; McNeill, J.; McQueen, A.; McShane, H.; Mears, C.; Megson, C.; Megson, S.; Mehta, P.; Meiring, J.; Melling, L.; Mencias, M.; Menzies, D.; Merida Morillas, M; Michael, A.; Miller, C.; Milligan, L.; Mills, C.; Mills, G.; Mills, N. L.; Milner, L.; Misra, S.; Mitchell, J.; Mohamed, A.; Mohamed, N.; Mohammed, S.; Molyneaux, P. L.; Monteiro, W.; Moriera, S.; Morley, A.; Morrison, L.; Morriss, R.; Morrow, A.; Moss, A. J.; Motohashi, K.; Msimanga, N.; Mukaetova-Ladinska, E.; Munawar, U.; Murira, J.; Nanda, U.; Nassa, H.; Nasseri, M.; Neal, A.; Needham, R.; Neill, P.; Neubauer, S.; Newby, D. E.; Newell, H.; Newman, T.; Newman, J.; Newton-Cox, A.; Nicholson, T.; Nicoll, D.; Nikolaidis, A.; Nolan, C. M.; Noonan, M. J.; Norman, C.; Novotny, P.; Nunag, J.; Nwafor, L.; Nwanguma, U.; Nyaboko, J.; O'Brien, C.; O'Donnell, K.; O'Regan, D.; O'Brien, L.; Odell, N.; Ogg, G.; Olaosebikan, O.; Oliver, C.; Omar, Z.; Orriss-Dib, L.; Osborne, L.; Osbourne, R.; Ostermann, M.; Overton, C.; Owen, J.; Oxton, J.; Pack, J.; Pacpaco, E.; Paddick, S.; Painter, S.; Pakzad, A.; Palmer, S.; Papineni, P.; Paques, K.; Paradowski, K.; Pareek, M.; Parekh, D.; Parfrey, H.; Pariante, C.; Parker, S.; Parmar, J.; Patale, S.; Patel, B.; Patel, M.; Patel, S.; Pattenadk, D.; Pavlides, M.; Payne, S.; Pearce, L.; Pearl, J. E.; Peckham, D.; Pendlebury, J.; Peng, Y.; Pennington, C.; Peralta, I.; Perkins, E.; Peterkin, Z.; Peto, T.; Petousi, N.; Petrie, J.; Pfeffer, P.; Phipps, J.; Pimm, J.; Piper Hanley, K; Pius, R.; Plant, H.; Plein, S.; Plekhanova, T.; Plowright, M.; Poinasamy, K.; Polgar, O.; Poll, L.; Porter, J. C.; Porter, J.; Portukhay, S.; Powell, N.; Prabhu, A.; Pratt, J.; Price, A.; Price, C.; Price, D.; Price, L.; Prickett, A.; Propescu, J.; Prosper, S.; Pugmire, S.; Quaid, S.; Quigley, J.; Quint, J.; Qureshi, H.; Qureshi, I. N.; Radhakrishnan, K.; Rahman, N. M.; Ralser, M.; Ramos, A.; Ramos, H.; Rangeley, J.; Rangelov, B.; Ratcliffe, L.; Ravencroft, P.; Reddington, A.; Reddy, R.; Reddy, A.; Redfearn, H.; Redwood, D.; Reed, A.; Rees, M.; Rees, T.; Regan, K.; Reynolds, W.; Ribeiro, C.; Richards, A.; Richardson, E.; Richardson, M.; Rivera-Ortega, P.; Roberts, K.; Robertson, E.; Robinson, E.; Robinson, L.; Roche, L.; Roddis, C.; Rodger, J.; Ross, A.; Ross, G.; Rossdale, J.; Rostron, A.; Rowe, A.; Rowland, A.; Rowland, J.; Rowland, M. J.; Rowland-Jones, S. L.; Roy, K.; Roy, M.; Rudan, I.; Russell, R.; Russell, E.; Saalmink, G.; Sabit, R.; Sage, E. K.; Samakomva, T.; Samani, N.; Sampson, C.; Samuel, K.; Samuel, R.; Sanderson, A.; Sapey, E.; Saralaya, D.; Sargent, J.; Sarginson, C.; Sass, T.; Sattar, N.; Saunders, K.; Saunders, R. M.; Saunders, P.; Saunders, L. C.; Savill, H.; Saxon, W.; Sayer, A.; Schronce, J.; Schwaeble, W.; Scott, J. T.; Scott, K.; Selby, N.; Semple, M. G.; Sereno, M.; Sewell, T. A.; Shah, A.; Shah, K.; Shah, P.; Shankar-Hari, M.; Sharma, M.; Sharpe, C.; Sharpe, M.; Shashaa, S.; Shaw, A.; Shaw, K.; Shaw, V.; Sheikh, A.; Shelton, S.; Shenton, L.; Shevket, K.; Shikotra, A.; Short, J.; Siddique, S.; Siddiqui, S.; Sidebottom, J.; Sigfrid, L.; Simons, G.; Simpson, J.; Simpson, N.; Singh, C.; Singh, S.; Singh, S. J.; Sissons, D.; Skeemer, J.; Slack, K.; Smith, A.; Smith, D.; Smith, S.; Smith, J.; Smith, L.; Soares, M.; Solano, T. S.; Solly, R.; Solstice, A. R.; Soulsby, T.; Southern, D.; Sowter, D.; Spears, M.; Spencer, L. G.; Speranza, F.; Stadon, L.; Stanel, S.; Steele, N.; Steiner, M.; Stensel, D.; Stephens, G.; Stephenson, L.; Stern, M.; Stewart, I.; Stimpson, R.; Stockdale, S.; Stockley, J.; Stoker, W.; Stone, R.; Storrar, W.; Storrie, A.; Storton, K.; Stringer, E.; Strong-Sheldrake, S.; Stroud, N.; Subbe, C.; Sudlow, C. L.; Suleiman, Z.; Summers, C.; Summersgill, C.; Sutherland, D.; Sykes, D. L.; Sykes, R.; Talbot, N.; Tan, A. L.; Tarusan, L.; Tavoukjian, V.; Taylor, A.; Taylor, C.; Taylor, J.; Te, A.; Tedd, H.; Tee, C. J.; Teixeira, J.; Tench, H.; Terry, S.; Thackray-Nocera, S.; Thaivalappil, F.; Thamu, B.; Thickett, D.; Thomas, C.; Thomas, D. C.; Thomas, S.; Thomas, A. K.; Thomas-Woods, T.; Thompson, T.; Thompson, A. A. R.; Thornton, T.; Thorpe, M.; Thwaites, R. S.; Tilley, J.; Tinker, N.; Tiongson, G. F.; Tobin, M.; Tomlinson, J.; Tong, C.; Toshner, M.; Touyz, R.; Tripp, K. A.; Tunnicliffe, E.; Turnbull, A.; Turner, E.; Turner, S.; Turner, V.; Turner, K.; Turney, S.; Turton, H.; Ugoji, J.; Ugwuoke, R.; Upthegrove, R.; Valabhji, J.; Ventura, M.; Vere, J.; Vickers, C.; Vinson, B.; Wade, E.; Wade, P.; Wainwright, T.; Wajero, L. O.; Walder, S.; Walker, S.; Wall, E.; Wallis, T.; Walmsley, S.; Walsh, J. A.; Walsh, S.; Warburton, L.; Ward, T. J. C.; Warwick, K.; Wassall, H.; Waterson, S.; Watson, E.; Watson, L.; Watson, J.; Weir McCall, J; Welch, C.; Welch, H.; Welsh, B.; Wessely, S.; West, S.; Weston, H.; Wheeler, H.; White, S.; Whitehead, V.; Whitney, J.; Whittaker, S.; Whittam, B.; Whitworth, V.; Wight, A.; Wild, J.; Wilkins, M.; Wilkinson, D.; Williams, B.; Williams, N.; Williams, J.; Williams-Howard, S. A.; Willicombe, M.; Willis, G.; Willoughby, J.; Wilson, A.; Wilson, D.; Wilson, I.; Window, N.; Witham, M.; Wolf-Roberts, R.; Wood, C.; Woodhead, F.; Woods, J.; Wootton, D. G.; Wormleighton, J.; Worsley, J.; Wraith, D.; Wrey Brown, C.; Wright, C.; Wright, L.; Wright, S.; Wyles, J.; Wynter, I.; Xu, M.; Yasmin, N.; Yasmin, S.; Yates, T.; Yip, K. P.; Young, B.; Young, S.; Young, A.; Yousuf, A. J.; Zawia, A.; Zeidan, L.; Zhao, B.; Zheng, B.; Zongo, O.
Source
Immunity & Ageing. January 11, 2024, Vol. 21 Issue 1
Subject
Language
English
ISSN
1742-4933
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 [+ or -] 11.30 years), moderate (n = 32; age 52.28 [+ or -] 11.43 years) or mild (n = 15; age 49.67 [+ or -] 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 [+ or -] 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.sup.-ve CD57.sup.+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.sup.+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 ([formula omitted] = 0.174, p = 0.043), with a major influence being disease severity ([formula omitted] = 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.
Author(s): Janet M. Lord[sup.1,2,3], Tonny Veenith[sup.3], Jack Sullivan[sup.1], Archana Sharma-Oates[sup.4], Alex G. Richter[sup.5], Neil J. Greening[sup.6], Hamish J. C. McAuley[sup.6], Rachael A. Evans[sup.6], Paul Moss[sup.5], Shona C. Moore[sup.7], Lance Turtle[sup.7], [...]
Author(s): Janet M. Lord[sup.1,2,3], Tonny Veenith[sup.3], Jack Sullivan[sup.1], Archana Sharma-Oates[sup.4], Alex G. Richter[sup.5], Neil J. Greening[sup.6], Hamish J. C. McAuley[sup.6], Rachael A. Evans[sup.6], Paul Moss[sup.5], Shona C. Moore[sup.7], Lance Turtle[sup.7], [...]