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

doi:10.1186/s12979-024-00430-7

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

Immun Ageing. 2024 May 7;21(1):28. doi: 10.1186/s12979-024-00430-7.

Authors

Johanne Poisson^#^{1

2

3}, Carine El-Sissy^#^{4

5

6}, Arnaud Serret-Larmande⁷, Nikaïa Smith⁸, Morgane Lebraud⁶, Jean-Loup Augy⁹, Catherine Conti^{1

2}, Cécile Gonnin^{6

10}, Benjamin Planquette¹¹, Jean-Benoît Arlet^{12

13}, Bertrand Hermann^{14

15}, Bruno Charbit¹⁶, Jean Pastre¹¹, Floriane Devaux⁶, Cyrielle Ladavière⁶, Lydie Lim⁶, Pauline Ober⁶, Johanna Cannovas², Lucie Biard⁷, Marie-Christelle Gulczynski¹⁷, Noémie Blumenthal⁶, Hélène Péré^{18

19

20}, Camille Knosp¹⁰, Alain Gey⁶, Nadine Benhamouda⁶, Juliette Murris²¹, David Veyer^{18

19}, Eric Tartour⁶, Jean-Luc Diehl^{14

22}, Darragh Duffy⁸, Elena Paillaud^{23

24

25}, Clémence Granier²⁶

Affiliations

¹ Université Paris Cité, Paris, France.
² Department of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HP, Paris, France.
³ Inserm U1149, Center for Research on Inflammation, Paris, France.
⁴ INSERM, Laboratory of Integrative Cancer Immunology, Paris, France.
⁵ Cordeliers Research Center, Sorbonne University, University Paris Cité, Paris, France.
⁶ Department of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP), Paris, France.
⁷ ECSTRRA Team, UMR-1153, Université Paris Cité, INSERM, AP-HP, Saint Louis Hospital, Paris, France.
⁸ Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.
⁹ Medical intensive care unit, Hopital Delafontaine, 2 rue du Dr Delafontaine, Saint-Denis, 93200, France.
¹⁰ Université Paris Cité, INSERM, PARCC, Paris, France.
¹¹ Service de Pneumologie Et Soins Intensifs, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
¹² Internal Medicine Department, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹³ Faculty of Medicine, Université Paris Cité, Paris, 75006, France.
¹⁴ Medical Intensive Care Unit, AP-HP. Centre Université Paris Cité, Georges Pompidou European Hospital, Paris, 75015, France.
¹⁵ INSERM UMR 1266, Institut de Psychiatrie Et Neurosciences de Paris (IPNP), Université Paris Cité, Paris, France.
¹⁶ Institute of Ophthalmology, University College London (UCL), London, UK.
¹⁷ Gérontologie 1, GHU AP-HP. Centre Université Paris Cité, Corentin Celton Hospital, Issy-Les-Moulineaux, 92130, France.
¹⁸ Virology Laboratory, Hôpital Européen Georges-Pompidou, APHP.Centre - Université Paris Cité, Paris, France.
¹⁹ Centre de Recherche Des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Functional Genomics of Solid Tumors Laboratory, Équipe Labellisée Ligue Nationale Contre Le Cancer, Labex OncoImmunology, Paris, France.
²⁰ Université Paris Cité, Faculté de Santé, UFR de Médecine, Paris, France.
²¹ HeKA, Inria Paris, Inserm, Université Paris Cité, Paris, France.
²² University Paris Cité, Innovative Therapies in Hemostasis, INSERM, Paris, 75006, France.
²³ Université Paris Cité, Paris, France. elena.paillaud@aphp.fr.
²⁴ Department of Geriatric Medicine, Hôpital Europeen Georges Pompidou, AP-HP, Paris, France. elena.paillaud@aphp.fr.
²⁵ Univ. Paris Est Créteil, Inserm U955, IMRB, Créteil, France. elena.paillaud@aphp.fr.
²⁶ Department of Immunology, APHP, Hôpital Européen Georges Pompidou (HEGP), Paris, France. clemence.granier@aphp.fr.

^# Contributed equally.

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.

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