Increased levels of GM-CSF and CXCL10 and low CD8(+) memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people

GM-CSF 和 CXCL10 水平升高以及 CD8(+) 记忆干细胞 T 细胞计数降低是老年人免疫衰老和重症 COVID-19 的标志。

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Abstract

BACKGROUND: Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8(+) T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity. RESULTS: One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1β, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8(+)T cells, and (ii) decreased early precursors CD8(+) T stem cell-like memory cells (TSCM) and CD27(+)CD28(+). The cytokines mentioned above were found at higher concentrations in the COVID-19(+) older cohort compared to a younger cohort in which they were not associated with disease severity. CONCLUSIONS: Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care.

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