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

Johanne Poisson (1, 2) , Carine El-Sissy (3, 2) , Arnaud Serret-Larmande (4) , Nikaïa Smith (5) , Morgane Lebraud (2) , Jean-Loup Augy (6) , Catherine Conti (7, 2) , Cécile Gonnin (8) , Benjamin Planquette (2) , Jean-Benoît Arlet (2) , Bertrand Hermann (2, 9) , Bruno Charbit (10) , Jean Pastre (2) , Floriane Devaux (2) , Cyrielle Ladavière (2) , Lydie Lim (2) , Pauline Ober (2) , Johanna Cannovas (2) , Lucie Biard (4) , Marie-Christelle Gulczynski (11) , Noémie Blumenthal (2) , Hélène Péré (2, 12, 13) , Camille Knosp (8) , Alain Gey (2) , Nadine Benhamouda (2) , Juliette Murris (14) , David Veyer (2, 13) , Eric Tartour (2) , Jean-Luc Diehl (12, 2) , Darragh Duffy (5) , Elena Paillaud (2, 15) , Clémence Granier (2)

1 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
2 HEGP - Hôpital Européen Georges Pompidou [APHP]
3 Immunologie et Cancérologie Intégratives = Integrative Cancer Immunology [CRC]
4 ECSTRRA [CRESS - U1153 / UMR_A 1125] - Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé
5 Immunologie Translationnelle - Translational Immunology lab
6 Hôpital Delafontaine
7 UPCité - Université Paris Cité
8 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
9 IPNP - U1266 Inserm - Institut de psychiatrie et neurosciences de Paris
10 UCL - University College of London [London]
11 Hôpital Corentin Celton [Issy-les-Moulineaux]
12 GHU AP-HP Centre Université Paris Cité
13 FunGeST - Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC]
14 HeKA - Health data- and model- driven Knowledge Acquisition
15 IMRB - Institut Mondor de Recherche Biomédicale

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.

Mots clés: CD8-positive T-lymphocytes; COVID-19; CXCL10; GMCSF; Geriatrics; Immune-ageing; Immunosenescence; Infections; Inflammaging; Senescence-associated secretory phenotype; TSCM

Domaines: Sciences du Vivant [q-bio]; Immunologie; Gériatrie et gérontologie; Maladies émergentes

Johanne Poisson, Carine El-Sissy, Arnaud Serret-Larmande, Nikaïa Smith, Morgane Lebraud, et al.. 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. Immunity and Ageing, 2024, 21 (1), pp.28. ⟨10.1186/s12979-024-00430-7⟩. ⟨pasteur-04574482⟩