TY - JOUR
AU - Lord, Janet M.
AU - Veenith, Tonny
AU - O'Sullivan, Jack W.
AU - Sharma-Oates, Archana
AU - Richter, Alex
AU - Greening, Neil J.
AU - McAuley, Hamish J.C.
AU - Evans, Rachael A.
AU - Moss, Paul
AU - Moore, Shona C.
AU - Turtle, Lance C.W.
AU - Gautam, Nandan
AU - Gilani, Ahmed
AU - Bajaj, Manan
AU - Wain, Louise V.
AU - Brightling, Christopher E.
AU - Raman, Betty
AU - Marks, Michael
AU - Singapuri, Amisha
AU - Elneima, Omer
AU - Openshaw, Peter J.M.
AU - Duggal, Niharika A.
PY - 2024
DA - January
TI - Accelerated immune ageing is associated with COVID-19 disease severity
JO - Immunity and Ageing
VL - 21
DO - https://doi.org/10.1186/s12979-023-00406-z
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 &lt; 0.0001); increased frequency of EMRA CD4 (p &lt; 0.003) and CD8 T cells (p &lt; 0.001); a higher frequency (p &lt; 0.0001) and absolute numbers (p &lt; 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p &lt; 0.003) and absolute numbers (p &lt; 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p &lt; 0.0001); higher frequency of memory B cells (p &lt; 0.001) and increased frequency (p &lt; 0.0001) and numbers (p &lt; 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 &lt; 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 ( = 0.174, p = 0.043), with a major influence being disease severity ( = 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.
PB - Springer Nature
UR - https://www.research.ed.ac.uk/en/publications/df97fcda-7785-4988-b0c0-be4ba19c5057
KW - Coronavirus (COVID-19)
KW - Older people
ER