Inflammatory markers and auto-Abs to type I IFNs in COVID-19 convalescent plasma cohort studyResearch in context
Fabrice Cognasse,
Hind Hamzeh-Cognasse,
Mickael Rosa,
Delphine Corseaux,
Brigitte Bonneaudeau,
Chloe Pierre,
Julie Huet,
Charles Antoine Arthaud,
Marie Ange Eyraud,
Amélie Prier,
Anne Claire Duchez,
Theo Ebermeyer,
Marco Heestermans,
Estelle Audoux-Caire,
Quentin Philippot,
Tom Le Voyer,
Olivier Hequet,
Anne-Marie Fillet,
Patricia Chavarin,
Dominique Legrand,
Pascale Richard,
France Pirenne,
Pierre Gallian,
Jean Laurent Casanova,
Sophie Susen,
Pascal Morel,
Karine Lacombe,
Paul Bastard,
Pierre Tiberghien
Affiliations
Fabrice Cognasse
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France; Corresponding author. Etablissement Français du Sang Auvergne-Rhône-Alpes, INSERM U1059, Campus Santé Innovation - 10 rue de la Marandière, 42270, Saint-Priest-en-Jarez, France.
Hind Hamzeh-Cognasse
Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Mickael Rosa
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, CNRS, U1011- EGID, F-59000 Lille, France; Centre National de la Recherche Scientifique (National Scientific Research Centre), Surgical Critical Care, Department of Anaesthesiology and Critical Care, U1019 - Unité Mixte de Recherche 9017 (Mixed Research Unit 9017) – Lille Centre for Infection and Immunity, France
Delphine Corseaux
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, CNRS, U1011- EGID, F-59000 Lille, France; Centre National de la Recherche Scientifique (National Scientific Research Centre), Surgical Critical Care, Department of Anaesthesiology and Critical Care, U1019 - Unité Mixte de Recherche 9017 (Mixed Research Unit 9017) – Lille Centre for Infection and Immunity, France
Brigitte Bonneaudeau
Etablissement Français du Sang, La Plaine, St Denis, France
Chloe Pierre
Etablissement Français du Sang, La Plaine, St Denis, France
Julie Huet
Etablissement Français du Sang, La Plaine, St Denis, France
Charles Antoine Arthaud
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Marie Ange Eyraud
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Amélie Prier
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Anne Claire Duchez
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Theo Ebermeyer
Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Marco Heestermans
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Estelle Audoux-Caire
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France; Univ Jean Monnet, Mines Saint-Étienne, INSERM, U 1059 Sainbiose, 42023, Saint-Étienne, France
Quentin Philippot
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163 (National Institute for Health and Medical Research), Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France
Tom Le Voyer
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163 (National Institute for Health and Medical Research), Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France
Olivier Hequet
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Anne-Marie Fillet
Etablissement Français du Sang, La Plaine, St Denis, France
Patricia Chavarin
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Dominique Legrand
Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Pascale Richard
Etablissement Français du Sang, La Plaine, St Denis, France
France Pirenne
Univ Paris Est Creteil, INSERM U955, Institut Mondor de Recherche Biomédicale (Mondor Biomedical Research Institute) (IMRB), Creteil, France & Laboratory of Excellence GR-Ex, Paris, France
Pierre Gallian
Etablissement Français du Sang, La Plaine, St Denis, France; UMR “Unité des Virus Emergents” (Emerging Virus Unit), Aix-Marseille University - IRD 190 - INSERM 1207 - IRBA - EFS - IHU Méditerranée Infection, Marseille, France
Jean Laurent Casanova
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163 (National Institute for Health and Medical Research), Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA
Sophie Susen
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, CNRS, U1011- EGID, F-59000 Lille, France; Centre National de la Recherche Scientifique (National Scientific Research Centre), Surgical Critical Care, Department of Anaesthesiology and Critical Care, U1019 - Unité Mixte de Recherche 9017 (Mixed Research Unit 9017) – Lille Centre for Infection and Immunity, France
Pascal Morel
Etablissement Français du Sang, La Plaine, St Denis, France
Etablissement Français du Sang, La Plaine, St Denis, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163 (National Institute for Health and Medical Research), Necker Hospital for Sick Children, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
Pierre Tiberghien
Etablissement Français du Sang, La Plaine, St Denis, France; UMR RIGHT U1098, INSERM, Etablissement Français du Sang, University of Franche-Comté, Besançon, France
Summary: Background: COVID-19 convalescent plasma (CCP) contains neutralising anti-SARS-CoV-2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients. Methods: CCP (n = 766) was compared to non-convalescent control plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralising auto-Abs to type I IFNs and reported adverse events in the recipients. Findings: CCP exhibited a statistically significant increase in IL-6 and TNF-alpha levels (0.531 ± 0.04 vs 0.271 ± 0.04; (95% confidence interval [CI], 0.07371–0.4446; p = 0.0061) and 0.900 ± 0.07 vs 0.283 ± 0.07 pg/mL; (95% [CI], 0.3097–0.9202; p = 0.0000829) and lower IL-10 (0.731 ± 0.07 vs 1.22 ± 0.19 pg/mL; (95% [CI], −0.8180 to −0.1633; p = 0.0034) levels than control plasma. Neutralising auto-Abs against type I IFNs were detected in 14/766 (1.8%) CCPs and were not associated with reported adverse events when transfused. Inflammatory markers and bioactivity in CCP with or without auto-Abs, or in CCP whether or not linked to adverse events in transfused patients, did not differ to a statistically significant extent. Interpretation: Overall, CCP exhibited moderately increased inflammatory markers compared to the control plasma with no discernible differences in ex-vivo bioactivity. Auto-Abs to type I IFNs detected in a small fraction of CCP were not associated with reported adverse events or differences in inflammatory markers. Additional studies, including careful clinical evaluation of patients treated with CCP, are required in order to further define the clinical relevance of these findings. Funding: French National Blood Service—EFS, the Association “Les Amis de Rémi” Savigneux, France, the “Fondation pour la Recherche Médicale (Medical Research Foundation)–REACTing 2020”.
