Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID‐19: An Observational Multicenter Study. Issue 6 (2nd July 2021)

• Record Type: Journal Article
• Authors: 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; Beeker, Nathanaël; Neuraz, Antoine; Gorwood, Philip; Alvarado, Jesús M.; Meneton, Pierre; Limosin, Frédéric
• Other Names: Ancel Pierre‐Yves investigator.; Bauchet Alain investigator.; Beeker Nathanaël investigator.; Benoit Vincent investigator.; Bernaux Mélodie investigator.; Bellamine Ali investigator.; Bey Romain investigator.; Bourmaud Aurélie investigator.; Breant Stéphane investigator.; Burgun Anita investigator.; Carrat Fabrice investigator.; Caucheteux Charlotte investigator.; Champ Julien investigator.; Cormont Sylvie investigator.; Daniel Christel investigator.; Dubiel Julien investigator.; Ducloas Catherine investigator.; Esteve Loic investigator.; Frank Marie investigator.; Garcelon Nicolas investigator.; Gramfort Alexandre investigator.; Griffon Nicolas investigator.; Grisel Olivier investigator.; Guilbaud Martin investigator.; Hassen‐Khodja Claire investigator.; Hemery François investigator.; Hilka Martin investigator.; Sophie Jannot Anne investigator.; Lambert Jerome investigator.; Layese Richard investigator.; Leblanc Judith investigator.; Lebouter Léo investigator.; Lemaitre Guillaume investigator.; Leprovost Damien investigator.; Lerner Ivan investigator.; Levi Sallah Kankoe investigator.; Maire Aurélien investigator.; Mamzer Marie‐France investigator.; Martel Patricia investigator.; Mensch Arthur investigator.; Moreau Thomas investigator.; Neuraz Antoine investigator.; Orlova Nina investigator.; Paris Nicolas investigator.; Rance Bastien investigator.; Ravera Hélène investigator.; Rozes Antoine investigator.; Salamanca Elisa investigator.; Sandrin Arnaud investigator.; Serre Patricia investigator.; Tannier Xavier investigator.; Treluyer Jean‐Marc investigator.; van Gysel Damien investigator.; Varoquaux Gaël investigator.; Vie Jill Jen investigator.; Wack Maxime investigator.; Wajsburt Perceval investigator.; Wassermann Demian investigator.; Zapletal Eric investigator.;
• Is Part Of: Clinical pharmacology & therapeutics. Volume 110:Issue 6(2021)
• Page Start: 1498
• Page End: 1511
• Publication Date: 2021-07-02
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.2317
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : 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 severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (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 an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an 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 end point occurred in 104 patients (37.5%) receiving an 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 (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58–0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46–0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID‐19 and support the continuation of FIASMA medications in these patients. Double‐blind controlled randomized clinical trials of these medications for COVID‐19 are needed.