1. Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID‐19: An Observational Multicenter Study
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Hoertel, Nicolas, Sánchez-Rico, Marina, Gulbins, Erich, Kornhuber, Johannes, Carpinteiro, Alexander, Lenze, Eric J., Reiersen, Angela M., Abellán, Miriam, de la Muela, Pedro, Vernet, Raphaël, Blanco, Carlos, Cougoule, Céline, Neuraz, Antoine, Gorwood, Philip, Alvarado, Jesús M., Meneton, Pierre, Limosin, Frédéric, Ancel, Pierre-Yves, Bauchet, Alain, Beeker, Nathanaël, Benoit, Vincent, Bernaux, Mélodie, Bellamine, Ali, Bey, Romain, Bourmaud, Aurélie, Breant, Stéphane, Burgun, Anita, Carrat, Fabrice, Caucheteux, Charlotte, Champ, Julien, Cormont, Sylvie, Daniel, Christel, Dubiel, Julien, Ducloas, Catherine, Esteve, Loic, Frank, Marie, Garcelon, Nicolas, Gramfort, Alexandre, Griffon, Nicolas, Grisel, Olivier, Guilbaud, Martin, Hassen-Khodja, Claire, Hemery, François, Hilka, Martin, Sophie Jannot, Anne, Lambert, Jerome, Layese, Richard, Leblanc, Judith, Lebouter, Léo, Lemaitre, Guillaume, Leprovost, Damien, Lerner, Ivan, Levi Sallah, Kankoe, Maire, Aurélien, Mamzer, Marie-France, Martel, Patricia, Mensch, Arthur, Moreau, Thomas, Orlova, Nina, Paris, Nicolas, Rance, Bastien, Ravera, Hélène, Rozes, Antoine, Salamanca, Elisa, Sandrin, Arnaud, Serre, Patricia, Tannier, Xavier, Treluyer, Jean-Marc, van Gysel, Damien, Varoquaux, Gaël, Vie, Jill Jen, Wack, Maxime, Wajsburt, Perceval, Wassermann, Demian, Zapletal, Eric, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Duisburg-Essen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Hôpital Européen Georges Pompidou [APHP] (HEGP), National Institute on Drug Abuse [Bethesda] (NIDA), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Institute on Drug Abuse [Bethesda], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Medizin ,law.invention ,Cohort Studies ,COVID-19 Testing ,medications ,Randomized controlled trial ,law ,Clinical endpoint ,Intubation ,Pharmacology (medical) ,Enzyme Inhibitors ,acid sphingomyelinase ,Aged, 80 and over ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,treatment ,Inverse probability weighting ,Hazard ratio ,Middle Aged ,3. Good health ,Hospitalization ,[SDV] Life Sciences [q-bio] ,Sphingomyelin Phosphodiesterase ,Female ,FIASMA ,Adult ,medicine.medical_specialty ,Adolescent ,intubation ,Young Adult ,Internal medicine ,Intubation, Intratracheal ,medicine ,Humans ,ceramide ,Aged ,Retrospective Studies ,Pharmacology ,SARS-CoV-2 ,Proportional hazards model ,business.industry ,COVID-19 ,mortality ,Confidence interval ,COVID-19 Drug Treatment ,Observational study ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, “Entrepôt de Données de Santé” AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal; International audience; Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p
- Published
- 2021
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