Accelerated immune ageing is associated with COVID-19 disease severity

Abstract

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 &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 ( $$\beta$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>β</mml:mi> </mml:math> = 0.174, p = 0.043), with a major influence being disease severity ( $$\beta$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>β</mml:mi> </mml:math> = 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.