Accelerated immune ageing is associated with COVID-19 disease severity

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 A.,Brown J.,Brown J.,Brown J. S.,Brown M.,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. 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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 C.,Price D.,Price L.,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.,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 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., ,

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

Aging,Immunology

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