학술논문

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
Document Type
Clinical report
Source
Immunity & Ageing. May 7, 2024, Vol. 21 Issue 1
Subject
Semiconductor memory
Memory (Computers)
Cytokines
Medical research
Medicine, Experimental
T cells
Stem cells
Diseases
Immune response
Vascular endothelial growth factor
Gerontology
Language
English
ISSN
1742-4933
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.sup.+ 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-1[beta], CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8.sup.+T cells, and (ii) decreased early precursors CD8.sup.+ T stem cell-like memory cells (TSCM) and CD27.sup.+CD28.sup.+. The cytokines mentioned above were found at higher concentrations in the COVID-19.sup.+ 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. Keywords: Immunosenescence, Inflammaging, Immune-ageing, COVID-19, Geriatrics, Infections, Senescence-associated secretory phenotype, CD8-positive T-lymphocytes, GMCSF, CXCL10, TSCM
Author(s): Johanne Poisson[sup.1,2,3], Carine El-Sissy[sup.4,5,6], Arnaud Serret-Larmande[sup.7], Nikaïa Smith[sup.8], Morgane Lebraud[sup.6], Jean-Loup Augy[sup.9], Catherine Conti[sup.1,2], Cécile Gonnin[sup.6,10], Benjamin Planquette[sup.11], Jean-Benoît Arlet[sup.12,13], Bertrand Hermann[sup.14,15], Bruno Charbit[sup.16], Jean Pastre[sup.11], Floriane Devaux[sup.6], Cyrielle [...]