Stéphanie Reynard1, Alexandra Journeaux1, Emilie Gloaguen2, Justine Schaeffer1, Hugo Varet3, Natalia Pietrosemoli3, Mathieu Mateo1, Nicolas Baillet1, Cédric Laouenan2,4, Hervé Raoul5, Jimmy Mullaert2, Sylvain Baize1. 1. Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Centre International de Recherche en Infectiologie, Université Lyon I, INSERM, CNRS, ENS Lyon, Lyon, France. 2. Infection Antimicrobials Modelling Evolution, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 3. Institut Pasteur, Hub Bioinformatique et Biostatistique, Centre de Bioinformatique, Biostatistique et Biologie Intégrative, C3BI, USR 3756 IP CNRS, Paris, France. 4. Assistance Publique - Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Paris, France. 5. Laboratoire P4 Jean Mérieux-INSERM, INSERM, Lyon, France.
Abstract
BACKGROUND: The West African Ebola virus epidemic from 2014-2016 highlighted the lack of knowledge about the pathogenicity of the virus and the factors responsible for outcome. A performant and rapid diagnosis is of crucial importance, as is overcoming the difficulty of providing high-quality patient management during such an extensive outbreak. Here, we propose to study the role of the immune mediators during Ebola virus disease and to define some molecules of importance in the outcome. METHODS: Plasma from Guinean patients sampled during the outbreak were analyzed using RT-qPCR, magnetic bead assay, ELISA, and high-quality statistical analyses. We also performed a transcriptomic analysis in leukocytes samples. Therefore, we deeply characterized the immune responses involved in Ebola virus disease. RESULTS: We evaluated the immune patterns depending on the outcome of the disease. Survivors presented an efficient and well-balanced immune response, whereas fatalities were characterized by an intense inflammatory response, overexpression of multiple cytokines, and a "chemokine storm." The plasma concentration of most of the parameters tested increased until death. Statistical analyses also allowed us to define a panel of markers highly predictive of outcome. CONCLUSION: The immune response observed in fatalities was highly similar to that characterizing septic shock syndrome. Our results suggest that immune responses can play a major pathogenic role during severe Ebola virus infection and argue in favor of therapeutic approaches that act on both viral replication and the induction of shock syndrome. FUNDING: French Ministry of Foreign Affairs, the Agence Française de Développement, and the Institut Pasteur.
BACKGROUND: The West African Ebola virus epidemic from 2014-2016 highlighted the lack of knowledge about the pathogenicity of the virus and the factors responsible for outcome. A performant and rapid diagnosis is of crucial importance, as is overcoming the difficulty of providing high-quality patient management during such an extensive outbreak. Here, we propose to study the role of the immune mediators during Ebola virus disease and to define some molecules of importance in the outcome. METHODS: Plasma from Guinean patients sampled during the outbreak were analyzed using RT-qPCR, magnetic bead assay, ELISA, and high-quality statistical analyses. We also performed a transcriptomic analysis in leukocytes samples. Therefore, we deeply characterized the immune responses involved in Ebola virus disease. RESULTS: We evaluated the immune patterns depending on the outcome of the disease. Survivors presented an efficient and well-balanced immune response, whereas fatalities were characterized by an intense inflammatory response, overexpression of multiple cytokines, and a "chemokine storm." The plasma concentration of most of the parameters tested increased until death. Statistical analyses also allowed us to define a panel of markers highly predictive of outcome. CONCLUSION: The immune response observed in fatalities was highly similar to that characterizing septic shock syndrome. Our results suggest that immune responses can play a major pathogenic role during severe Ebola virus infection and argue in favor of therapeutic approaches that act on both viral replication and the induction of shock syndrome. FUNDING: French Ministry of Foreign Affairs, the Agence Française de Développement, and the Institut Pasteur.
Authors: Helen R Wagstaffe; Elizabeth A Clutterbuck; Viki Bockstal; Jeroen N Stoop; Kerstin Luhn; Macaya Douoguih; Georgi Shukarev; Matthew D Snape; Andrew J Pollard; Eleanor M Riley; Martin R Goodier Journal: J Clin Invest Date: 2020-07-01 Impact factor: 14.808
Authors: Patrick Younan; Rodrigo I Santos; Palaniappan Ramanathan; Mathieu Iampietro; Andrew Nishida; Mukta Dutta; Tatiana Ammosova; Michelle Meyer; Michael G Katze; Vsevolod L Popov; Sergei Nekhai; Alexander Bukreyev Journal: PLoS Pathog Date: 2019-10-24 Impact factor: 6.823
Authors: Tzanko S Stantchev; Autumn Zack-Taylor; Nicholas Mattson; Klaus Strebel; Christopher C Broder; Kathleen A Clouse Journal: Viruses Date: 2019-09-23 Impact factor: 5.048