@article{5cfcb9133043405991e3b7f4bb64e670,
title = "Accelarated immune ageing is associated with COVID-19 disease severity",
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 na{\"i}ve 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 (β = 0.174, p = 0.043), with a major influence being disease severity (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.",
author = "{on behalf of the PHOSP-COVID Study collaborative group} and {ISARIC4C Investigators} and K. Abel and S. Ahmad and R. Ahmed and M. Ali and Allen, {R. J.} and P. Almeida and D. Anderson and L. Armstrong and N. Armstrong and M. Ashworth and A. Ayoub and R. Baggott and L. Bailey and D. Baldwin and C. Ballard and A. Banerjee and A. Bates and M. Begum and D. Bell and R. Bell and C. Berry and K. Bhui and K. Bramham and G. Breen and C. Brookes and M. Broome and A. Brown and A. Brown and J. Brown and J. Brown and J. Brown and M. Brown and M. Brown and A. Burns and A. Butt and S. Byrne and G. Carson and P. Carter and T. Chalder and CHambers, {R. C.} and F. Chan and J. Chen and Y. Cheng and A. Chiribiri and N. Choudhury and P. Chowienczyk and D. Clark and C. Clark and J. Clarke and J. Cole and C. Coleman and B. Connolly and L. Connor and A. Cook and B. Cooper and J. Cooper and S. Cooper and T. Craig and A. Cross and A. David and E. Davies and G. Davies and G. Davies and K. Davies and Davies, {M. J.} and J. Dawson and A. Donaldson and T. Dong and A. Dougherty and R. Dowling and S. Dunn and S. Edwards and A. Elliott and K. Elliott and D. Evans and H. Evans and J. Evans and Evans, {R. I.} and Evans, {R. I.} and T. Evans and J. Finch and H. Fisher and M. Flynn and A. Ford and R. Francis and X. Fu and M. Gill and C. Goodwin and B. Gooptu and H. Gregory and R. Gregory and D. Grieve and L. Griffiths and A. Gupta and L. Hall and E. Harris and Harris, {V. C.} and P. Harrison and N. Hart and A. Harvey and M. Harvey and A. Hayday and M. Henderson and Ho, {L. P.} and S. Holden and M. Holland and M. Holmes and A. Hosseini and M. Hotopf and Howard, {L. S.} and Hughes, {A. D.} and J. Hughes and R. Hughes and M. Husain and K. Ismail and T. Jackson and J. Jacob and James, {W. Y.} and Jenkins, {R. G.} and C. Johnson and S. Johnson and Jolley, {C. J.} and D. Jones and G. Jones and H. Jones and H. Jones and I. Jones and L. Jones and Jones, {M. G.} and S. Jones and S. Jose and G. Kaltsakas and S. Kelly and S. Kerr and F. Khan and B. King and S. Knight and Kon, {S. S.} and Kon, {S. S.} and C. Laing and D. Lasserson and C. Lawson and C. Lawson and D. Lee and Lee, {J. H.} and D. Lewis and J. Lewis and X. Li and L. Lim and A. Lloyd and E. Major and M. Malim and Man, {W. D.C.} and S. Mandal and K. Mangion and S. Marsh and B. Marshall and M. Marshall and J. Martin and Martinez, {L. M.} and McMahon, {M. J.} and P. Mehta and C. Miller and C. Mills and J. Mitchell and A. Mohamed and S. Mohammed and A. Morley and A. Morrow and Moss, {A. J.} and A. Neal and Newby, {D. E.} and J. Newman and T. Nicholson and M. Ostermann and J. Owen and C. Pariante and S. Parker and B. Patel and M. Patel and S. Patel and S. Payne and L. Pearce and Y. Peng and C. Pennington and P. Pfeffer and H. Plant and S. Plein and Porter, {J. C.} and J. Porter and N. Powell and J. Pratt and A. Price and C. Price and C. Price and D. Price and A. Prickett and J. Quigley and Qureshi, {I. N.} and Rahman, {N. M.} and A. Reddy and M. Rees and T. Rees and W. Reynolds and A. Richards and E. Richardson and M. Richardson and K. Roberts and E. Robertson and E. Robinson and L. Robinson and J. Rodger and A. Ross and A. Rowe and A. Rowland and J. Rowland and R. Russell and Sage, {E. K.} and K. Saunders and Saunders, {R. M.} and P. Saunders and Scott, {J. T.} and A. Shah and K. Shah and P. Shah and M. Shankar-Hari and M. Sharma and C. Sharpe and A. Shaw and K. Shaw and J. Simpson and C. Singh and S. Singh and S. Singh and A. Smith and D. Smith and S. Smith and J. Smith and L. Smith and Spencer, {L. G.} and L. Stephenson and I. Stewart and S. Stockdale and R. Stone and Tan, {A. L.} and A. Taylor and C. Taylor and J. Taylor and S. Terry and C. Thomas and Thomas, {D. C.} and S. Thomas and Thomas, {A. K.} and T. Thompson and Thompson, {A. A.R.} and J. Tilley and J. Tomlinson and S. Turner and K. Turner and P. Wade and T. Wainwright and S. Walker and S. Walker and Walsh, {J. A.} and S. Walsh and Ward, {T. J.C.} and E. Watson and L. Watson and J. Watson and {Weir McCall}, J. and C. Welch and S. Wessely and S. West and S. White and J. Whitney and S. Whittaker and J. Wild and B. Williams and N. Williams and N. Williams and J. Williams and J. Willoughby and A. Wilson and D. Wilson and I. Wilson and C. Wood and J. Woods and C. Wright and L. Wright and S. Wright and M. Xu and Yip, {K. P.} and B. Young and S. Young and A. Young and B. Zhao and B. Zheng",
note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",
year = "2024",
month = jan,
day = "11",
doi = "10.1186/s12979-023-00406-z",
language = "English",
volume = "21",
journal = "Immunity and Ageing",
issn = "1742-4933",
publisher = "BioMed Central",
number = "1",
}
