Accelarated immune ageing is associated with COVID-19 disease severity.


Lord, Janet M, Veenith, Tonny, Sullivan, Jack, Sharma-Oates, Archana, Richter, Alex G, Greening, Neil J, McAuley, Hamish JC, Evans, Rachael A, Moss, Paul, Moore, Shona C ORCID: 0000-0001-8610-2806 et al (show 14 more authors) (2024) Accelarated immune ageing is associated with COVID-19 disease severity. Immunity & ageing : I & A, 21 (1). 6-.

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Abstract

<h4>Background</h4>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.<h4>Results</h4>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 ([Formula: see text] = 0.174, p = 0.043), with a major influence being disease severity ([Formula: see text] = 0.188, p = 0.01).<h4>Conclusions</h4>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 and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 30 Jan 2024 09:51
Last Modified: 30 Jan 2024 10:59
DOI: 10.1186/s12979-023-00406-z
Open Access URL: https://doi.org/10.1186/s12979-023-00406-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3178066
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