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

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Poisson, Johanne | El-Sissy, Carine | Serret-Larmande, Arnaud | Smith, Nikaïa | Lebraud, Morgane | Augy, Jean-Loup | Conti, Catherine | Gonnin, Cécile | Planquette, Benjamin | Arlet, Jean-Benoît | Hermann, Bertrand | Charbit, Bruno | Pastre, Jean | Devaux, Floriane | Ladavière, Cyrielle | Lim, Lydie | Ober, Pauline | Cannovas, Johanna | Biard, Lucie | Gulczynski, Marie-Christelle | Blumenthal, Noémie | Péré, Hélène | Knosp, Camille | Gey, Alain | Benhamouda, Nadine | Murris, Juliette | Veyer, David | Tartour, Eric | Diehl, Jean-Luc | Duffy, Darragh | Paillaud, Elena | Granier, Clémence

Edité par CCSD ; BioMed Central -

International audience. 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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