Accelarated immune ageing is associated with COVID-19 disease severity.
Lord JM., Veenith T., Sullivan J., Sharma-Oates A., Richter AG., Greening NJ., McAuley HJC., Evans RA., Moss P., Moore SC., Turtle L., Gautam N., Gilani A., Bajaj M., Wain LV., Brightling C., Raman B., Marks M., Singapuri A., Elneima O., Openshaw PJM., Duggal NA., PHOSP-COVID Study collaborative group None., ISARIC4C investigators None.
BackgroundThe 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.ResultsWe 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 -ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p +ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p ConclusionsOur 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.