Accelerated 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 J C; Evans, Rachael A; Moss, Pal; 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; on behalf of the PHOSP-COVID Study collaborative group; ISARIC4C investigators; Bolton, Charlotte E

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 3–5months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30years), moderate (n = 32; age 52.28 ± 11.43years) or mild (n = 15; age 49.67 ± 7.30years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68years). 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 (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.

• Journal Article Type: Article
• Acceptance Date: Feb 14, 2024
• Online Publication Date: Jan 11, 2024
• Publication Date: 2024-01
• Deposit Date: Feb 29, 2024
• Publicly Available Date: Feb 29, 2024
• Journal: Immunity and Ageing
• Electronic ISSN: 1742-4933
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: 1
• Article Number: 6
• DOI: https://doi.org/10.1186/s12979-023-00406-z
• Keywords: Aging; Immunology
• Public URL: https://nottingham-repository.worktribe.com/output/29840993
• PMID: 38212801
• Additional Information: Received: 4 July 2023; Accepted: 18 December 2023; First Online: 11 January 2024; : ; : The severe COVID patients were recruited in Birmingham as part of the Coronavirus Immunological Analysis study approved by North West Preston Research Ethics Committee (20/NW/0240). The moderate disease patients were recruited as part of the PHOSP-COVID study approved by Leeds West Research Ethics Committee (20/YH/0225) and the Human Immune Responses to Acute Virus Infections study (16/NW/0170) approved by North West—Liverpool Central Research Ethics Committee. The mild disease cohort were recruited as part of the COVID in the Community study approved by the London Camden & Kings Cross Research Ethics Committee (20/HRA/1817).; : All authors provide consent for the publication of the research findings of the study.; : The authors declare no competing interests.