T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19
Fabienne Venet,
Morgane Gossez,
Frank Bidar,
Maxime Bodinier,
Rémy Coudereau,
Anne-Claire Lukaszewicz,
Claire Tardiveau,
Karen Brengel-Pesce,
Valérie Cheynet,
Marie-Angélique Cazalis,
Rémi Pescarmona,
Lorna Garnier,
Marine Ortillon,
Marielle Buisson,
Maude Bouscambert-Duchamp,
Florence Morfin-Sherpa,
Jean-Sébastien Casalegno,
Filippo Conti,
Thomas Rimmelé,
Laurent Argaud,
Martin Cour,
Mitra Saadatian-Elahi,
Laetitia Henaff,
Philippe Vanhems,
Guillaume Monneret
Affiliations
Fabienne Venet
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Corresponding author at: Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France.
Morgane Gossez
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France
Frank Bidar
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France; Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon 69437, France
Maxime Bodinier
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Rémy Coudereau
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France; EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Anne-Claire Lukaszewicz
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France; Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon 69437, France
Claire Tardiveau
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Karen Brengel-Pesce
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Valérie Cheynet
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Marie-Angélique Cazalis
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Rémi Pescarmona
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Immunology Laboratory, Lyon-Sud University Hospital - Hospices Civils de Lyon, Pierre-Bénite, France
Lorna Garnier
Immunology Laboratory, Lyon-Sud University Hospital - Hospices Civils de Lyon, Pierre-Bénite, France
Marine Ortillon
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France
Marielle Buisson
Centre d'Investigation Clinique de Lyon (CIC 1407 Inserm), Hospices Civils de Lyon, Lyon F-69677, France
Maude Bouscambert-Duchamp
Virology Laboratory, CNR des virus des infections Respiratoires, Institut des Agents Infectieux, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon, France
Florence Morfin-Sherpa
Virology Laboratory, CNR des virus des infections Respiratoires, Institut des Agents Infectieux, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon, France
Jean-Sébastien Casalegno
Virology Laboratory, CNR des virus des infections Respiratoires, Institut des Agents Infectieux, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon, France
Filippo Conti
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Thomas Rimmelé
EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France; Anesthesia and Critical Care Medicine Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon 69437, France
Laurent Argaud
Medical intensive Care Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69437, France
Martin Cour
Medical intensive Care Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69437, France
Mitra Saadatian-Elahi
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service Hygiène, Epidémiologie, Infectiovigilance et Prévention, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69437, France
Laetitia Henaff
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service Hygiène, Epidémiologie, Infectiovigilance et Prévention, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69437, France
Philippe Vanhems
Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard-Lyon 1, Lyon, France; Service Hygiène, Epidémiologie, Infectiovigilance et Prévention, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69437, France
Guillaume Monneret
Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, Lyon 69437 CEDEX 03, France; EA 7426 ''Pathophysiology of Injury-Induced Immunosuppression'' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Lyon 69003, France
Summary: Background: In critically ill COVID-19 patients, the initial response to SARS-CoV-2 infection is characterized by major immune dysfunctions. The capacity of these severe patients to mount a robust and persistent SARS-CoV-2 specific T cell response despite the presence of severe immune alterations during the ICU stay is unknown. Methods: Critically ill COVID-19 patients were sampled five times during the ICU stay and 9 and 13 months afterwards. Immune monitoring included counts of lymphocyte subpopulations, HLA-DR expression on monocytes, plasma IL-6 and IL-10 concentrations, anti-SARS-CoV-2 IgG levels and T cell proliferation in response to three SARS-CoV-2 antigens. Findings: Despite the presence of major lymphopenia and decreased monocyte HLA-DR expression during the ICU stay, convalescent critically ill COVID-19 patients consistently generated adaptive and humoral immune responses against SARS-CoV-2 maintained for more than one year after hospital discharge. Patients with long hospital stays presented with stronger anti-SARS-CoV-2 specific T cell response but no difference in anti-SARS-CoV2 IgG levels. Interpretation: Convalescent critically ill COVID-19 patients consistently generated a memory immune response against SARS-CoV-2 maintained for more than one year after hospital discharge. In recovered individuals, the intensity of SARS-CoV-2 specific T cell response was dependent on length of hospital stay. Funding: This observational study was supported by funds from the Hospices Civils de Lyon, Fondation HCL, Claude Bernard Lyon 1 University and Région Auvergne Rhône-Alpes and by partial funding by REACTing (Research and ACTion targeting emerging infectious diseases) INSERM, France and a donation from Fondation AnBer (http://fondationanber.fr/).