Accelerated immune ageing is associated with COVID-19 disease severity
Janet M. Lord, Tonny Veenith, Jack Sullivan, Archana Sharma‐Oates, Alex Richter, Neil Greening, Hamish McAuley, Rachael A Evans, Paul Moss, Shona C. Moore, Lance Turtle, Nandan Gautam, Ahmed Gilani, Manan Bajaj, Louise V. Wain, Christopher E. Brightling, Betty Raman, Michael Marks, Amisha Singapuri, Omer Elneima, Peter Openshaw, Niharika A. Duggal, on behalf of the PHOSP-COVID Study collaborative group, Kathryn M. Abel, Huzaifa Adamali, Davies Adeloye, O Adeyemi, R Adrego, L Aguilar-Jimenez, Sohail Ahmad, Nafees Haider, Rizwan Ahmed, N Ahwireng, Mark Ainsworth, B Al-Sheklly, A Alamoudi, Mohammad Ali, M Aljaroof, A.M. All, Louise Allan, Richard J. Allen, L. Allerton, Lynne Allsop, P. Almeida, Doris Altmann, Maria Alvarez Corral, S Amoils, Debra Anderson, Chrystalina A. Antoniades, G. Arbane, Ana Arias, Chérie Armour, Lará Armstrong, Natalie Armstrong, David Arnold, H Arnold, Abdul Ashish, Andrew Ashworth, Mark Ashworth, S Aslani, H Assefa-Kebede, Catherine Atkin, Philip A. Atkin, Raminder Aul, Htin Aung, Luke Austin, Cristina Avram, A Ayoub, Marta Babores, Rob Baggott, J. Bagshaw, David Baguley, L. Charles Bailey, J. Kenneth Baillie, S. Bain, M Bakali, M Bakau, Eileen Baldry, David Baldwin, Molly M Baldwin, Clive Ballard, Amitava Banerjee, B. Bang, Ruth E Barker, L Barman, Shaney Barratt, Fiona Barrett, D Basire, N Basu, M. Bates, Andrew Bates, Rachel L. Batterham, Helen Baxendale, Hannah Bayes, Michael Beadsworth, P Beckett, M. Beggs, M Begum, Paul Beirne, D Bell
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 < 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 ( $$\beta$$ <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.