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Accelerated immune ageing is associated with COVID-19 disease severity
Lord, Janet M Sullivan, Jack Sharma-Oates, Archana Richter, Alex G Greening, Neil J McAuley, Hamish J C Evans, Rachael A Moss, Paul Moore, Shona C
Lord, Janet M
Sullivan, Jack
Sharma-Oates, Archana
Richter, Alex G
Greening, Neil J
McAuley, Hamish J C
Evans, Rachael A
Moss, Paul
Moore, Shona C
Authors
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
PHOSP-COVID Study collaborative group
ISARIC4C investigators
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
PHOSP-COVID Study collaborative group
ISARIC4C investigators
Editors
Other contributors
Affiliation
Epub Date
Issue Date
2024-01-11
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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.
Citation
Lord, J.M., Veenith, T., Sullivan, J. et al. Accelerated immune ageing is associated with COVID-19 disease severity. Immun Ageing 21, 6 (2024). https://doi.org/10.1186/s12979-023-00406-z
Publisher
Journal
Research Unit
PubMed ID
38212801 (pubmed)
PubMed Central ID
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Type
Journal article
Language
en
Description
© 2024 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s12979-023-00406-z
Series/Report no.
ISSN
1742-4933
EISSN
1742-4933
ISBN
ISMN
Gov't Doc #
Sponsors
This work was supported by funding from the Medical Research Council supported UK Coronavirus Immunology Consortium and the National Institute for Health Research (NIHR) supported PHOSP-COVID Collaborative study. The funders provided financial support to this research but had no role in the design of the study, analysis, interpretations of the data and in writing the manuscript.
Rights
Licence for published version: Creative Commons Attribution 4.0 International