494 research outputs found

    Accelarated immune ageing is associated with COVID-19 disease severity

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    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 ( = 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

    Measurement of single top-quark production in the s-channel in proton–proton collisions at s \sqrt{s} = 13 TeV with the ATLAS detector

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    International audienceA measurement of single top-quark production in the s-channel is performed in proton–proton collisions at a centre-of-mass energy of 13 TeV with the ATLAS detector at the CERN Large Hadron Collider. The dataset corresponds to an integrated luminosity of 139 fb1^{−1}. The analysis is performed on events with an electron or muon, missing transverse momentum and exactly two b-tagged jets in the final state. A discriminant based on matrix element calculations is used to separate single-top-quark s-channel events from the main background contributions, which are top-quark pair production and W-boson production in association with jets. The observed (expected) signal significance over the background-only hypothesis is 3.3 (3.9) standard deviations, and the measured cross-section is σ=8.22.9+3.5 \sigma ={8.2}_{-2.9}^{+3.5} pb, consistent with the Standard Model prediction of σSM=10.320.36+0.40 {\sigma}^{\textrm{SM}}={10.32}_{-0.36}^{+0.40} pb.[graphic not available: see fulltext