TY - JOUR
T1 - Accelarated immune ageing is associated with COVID-19 disease severity
AU - on behalf of the PHOSP-COVID Study collaborative group
AU - ISARIC4C Investigators
AU - Lord, Janet M.
AU - Veenith, Tonny
AU - Sullivan, Jack
AU - Sharma-Oates, Archana
AU - Richter, Alex G.
AU - Greening, Neil J.
AU - McAuley, Hamish J.C.
AU - Evans, Rachael A.
AU - Moss, Paul
AU - Moore, Shona C.
AU - Turtle, Lance
AU - Gautam, Nandan
AU - Gilani, Ahmed
AU - Bajaj, Manan
AU - Wain, Louise V.
AU - Brightling, Christopher
AU - Raman, Betty
AU - Marks, Michael
AU - Singapuri, Amisha
AU - Elneima, Omer
AU - Openshaw, Peter J.M.
AU - Duggal, Niharika A.
AU - Abel, K.
AU - Adamali, H.
AU - Adeloye, D.
AU - Adeyemi, O.
AU - Adrego, R.
AU - AguilarJimenez, L. A.
AU - Ahmad, S.
AU - Ahmad Haider, N.
AU - Ahmed, R.
AU - Ahwireng, N.
AU - Ainsworth, M.
AU - Al-Sheklly, B.
AU - Alamoudi, A.
AU - Ali, M.
AU - Aljaroof, M.
AU - All, A. M.
AU - Allan, L.
AU - Allen, R. J.
AU - Allerton, L.
AU - Allsop, L.
AU - Almeida, P.
AU - Altmann, D.
AU - Alvarez Corral, M.
AU - Amoils, S.
AU - Anderson, D.
AU - Antoniades, C.
AU - Carson, G.
AU - Robinson, E.
N1 - Publisher Copyright:
© 2024, The Author(s).
PY - 2024/12
Y1 - 2024/12
N2 - 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−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.
AB - 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−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.
UR - https://www.scopus.com/pages/publications/85182145161
U2 - 10.1186/s12979-023-00406-z
DO - 10.1186/s12979-023-00406-z
M3 - Article
AN - SCOPUS:85182145161
SN - 1742-4933
VL - 21
JO - Immunity and Ageing
JF - Immunity and Ageing
IS - 1
M1 - 6
ER -