Accelarated immune ageing is associated with COVID-19 disease severity

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Lord, JM, Veenith, T, Sullivan, J, Sharma-Oates, A, Richter, AG, Greening, NJ, McAuley, HJC, Evans, RA, Moss, P, Moore, SC ORCID: 0000-0001-8610-2806 et al (show 90 more authors) , Turtle, L ORCID: 0000-0002-0778-1693, Gautam, N, Gilani, A, Bajaj, M, Wain, LV, Brightling, C, Raman, B, Marks, M, Singapuri, A, Elneima, O, Openshaw, PJM, Duggal, NA, Abel, K, Adamali, H, Adeloye, D, Adeyemi, O, Adrego, R, AguilarJimenez, LA, Ahmad, S, Ahmad Haider, N, Ahmed, R, Ahwireng, N, Ainsworth, M, Al-Sheklly, B, Alamoudi, A, Ali, M, Aljaroof, M, All, AM, Allan, L, Allen, RJ, 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, JK, Bain, S, Bakali, M, Bakau, M, Baldry, E, Baldwin, D, Baldwin, M, Ballard, C, Banerjee, A, Bang, B, Barker, RE, 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 and Bell, R (2024) Accelarated immune ageing is associated with COVID-19 disease severity Immunity and Ageing, 21 (1). 6-. ISSN 1742-4933, 1742-4933

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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<sup>−ve</sup> CD57<sup>+ve</sup> 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</sup> 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.

Item Type:	Article
Uncontrolled Keywords:	PHOSP-COVID Study collaborative group, ISARIC4C investigators
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	30 Jan 2024 09:51
Last Modified:	22 Jan 2026 13:33
DOI:	10.1186/s12979-023-00406-z
Open Access URL:	https://doi.org/10.1186/s12979-023-00406-z
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178066
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