Rauch, Antoine, Dupont, Annabelle, GOUTAY, Julien, Caplan, Morgan, Staessens, Senna, Moussa, Mouhamed, Jeanpierre, Emmanuelle, Corseaux, Delphine, Lefevre, Guillaume, Lassalle, Fanny, Faure, Karine, Lambert, Marc, Duhamel, Alain, Labreuche, Julien, Garrigue, Delphine, De Meyer, Simon F., Staels, Bart, Van Belle, Eric, Vincent, Flavien, Kipnis, Eric, Lenting, Peter J., Poissy, Julien, Susen, Sophie, Research Network (LICORNE), For the Lille COVID, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Université Catholique de Louvain = Catholic University of Louvain (UCL), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), This study was supported by the French government through the Program Investissement d’Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE)., Members of the LICORNE Scientific Committee: Dominique Deplanque (Clinical Investigation Center, CHU Lille, France) Karine Faure (Department of Infectious Diseases, CHU Lille, France) Guillaume Lefevre (Department of Immunology, CHU Lille, France) Enagnon Kazali Alidjinou (Department of Virology, CHU Lille, France) Régis Bordet (Department of Medical Pharmacology, CHU Lille, France) Marie-Charlotte Chopin (Department of Infectious Diseases, CHU Lille, France) Ilka Engelmann (Department of Virology, CHU Lille, France) Delphine Garrigue (Department of Emergency, CHU Lille, France) Anne Goffard (Department of Virology, CHU Lille, France) Eric Kipnis (Department of Anesthesia and Critical Care, CHU Lille, France) Myriam Labalette (Department of Immunology, CHU Lille, France) Marc Lambert (Department of Internal Medicine, CHU Lille, France) David Launay (Department of Internal Medicine, CHU Lille, France) Daniel Mathieu (Department of Intensive Care, CHU Lille, France) Claude-Alain Maurage (Department of Anatomopathology, CHU Lille, France) Julien Poissy (Department of Intensive Care, CHU Lille, France) Boualem Sendid (Department of Parasitology, CHU Lille, France) Sophie Susen (Department of Hematology, CHU Lille, France), ANR-16-IDEX-0004,ULNE,ULNE(2016), Université de Lille, LillOA, ULNE - - ULNE2016 - ANR-16-IDEX-0004 - IDEX - VALID, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
This article assessed whether plasma collected from patients with COVID-19 at different disease stages could trigger endothelial damage in vitro by using cultured human pulmonary microvascular endothelial cells (HPMVEC) This study also further investigated the association of plasma-induced cytotoxicity with levels of circulating biomarkers related to organ dysfunction (Pao2 [partial pressure of oxygen in arterial blood]/Fio2 [fraction of inspired oxygen], widely used as an indicator of oxygenation requirements, lactate dehydrogenase, creatinine, and aspartate transaminase), endothelial damage (von Willebrand factor antigen;ADAMTS13;plasminogen activator inhibitor-1;syndecan-1), tissue injury (cell-free DNA, a damage-associated molecular patterns marker), and levels of circulating cytokines related to the activation of innate (interleukin [IL]-6 and tumor necrosis factor-a) and adaptative immune cell responses (soluble IL-2 receptor) Inclusion criteria were individuals aged 18 years or older with a positive SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasal or tracheal samples This data shed new light on the pathophysiology of COVID-19 by demonstrating the direct and rapid cytotoxic effect of plasma collected from critically ill patients on vascular endothelial cells This rapid effect (1 hour after plasma exposure) excludes a direct cytopathic effect of SARS-CoV-2 infection, as the progression of viral infection and visible cytopathogenic effects are in general only apparent 12 to 24 hours after infection 5 A higher cytotoxic effect of plasma on endothelial cells was associated with a more pronounced hypoxemia and organ dysfunction as reflected by the correlation with Pao2/FiO2, lactate dehydrogenase, creatinine, and aspartate transaminase This cytotoxic effect also correlated with circulating markers of endothelial damage, indicating that this in vitro functional assay reflects microvascular endothelial damage in vivo Different pathways could be involved in endothelial cell injury during the course of COVID-19, i e , complement activation, cellular hypoxia, platelets, and direct cytotoxicity of cytokines such as IL-6, IL-1beta, and tumor necrosis factor-a The study observed a relationship between this cytotoxic effect and the level of proinflammatory cytokines, suggesting that cytotoxicity could be related to overproduction of proinflammatory cytokines