Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study

DOI record: { "DOI": "10.3390/ph16081107", "ISSN": [ "1424-8247" ], "URL": "http://dx.doi.org/10.3390/ph16081107", "abstract": "<jats:p>Prior evidence indicates the potential central role of the acid sphingomyelinase (ASM)/ceramide system in the infection of cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 36 AP-HP (Assistance Publique–Hôpitaux de Paris) hospitals from 2 May 2020 to 31 August 2022. We examined the association between the ongoing use of medications functionally inhibiting acid sphingomyelinase (FIASMA), which reduces the infection of cells with SARS-CoV-2 in vitro, upon hospital admission with 28-day all-cause mortality in a 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other medications (N = 9714). The univariate Cox regression model of the matched analytic sample showed that FIASMA medication use at admission was associated with significantly lower risks of 28-day mortality (HR = 0.80; 95% CI = 0.72–0.88; p &lt; 0.001). In this multicenter observational study, the use of FIASMA medications was significantly and substantially associated with reduced 28-day mortality among adult patients hospitalized with COVID-19. These findings support the continuation of these medications during the treatment of SARS-CoV-2 infections. Randomized clinical trials (RCTs) are needed to confirm these results, starting with the molecules with the greatest effect size in the study, e.g., fluoxetine, escitalopram, and amlodipine.</jats:p>", "alternative-id": [ "ph16081107" ], "author": [ { "ORCID": "http://orcid.org/0000-0002-7890-1349", "affiliation": [ { "name": "INSERM U1266, Université Paris Cité, F-75014 Paris, France" }, { "name": "Service de Psychiatrie et Addictologie de l’adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France" } ], "authenticated-orcid": false, "family": "Hoertel", "given": "Nicolas", "sequence": "first" }, { "affiliation": [ { "name": "Service de Psychiatrie et Addictologie de l’adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France" } ], "family": "Rezaei", "given": "Katayoun", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1121-8641", "affiliation": [ { "name": "Service de Psychiatrie et Addictologie de l’adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France" }, { "name": "Department of Psychobiology and Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, F-28223 Madrid, Spain" } ], "authenticated-orcid": false, "family": "Sánchez-Rico", "given": "Marina", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1889-4503", "affiliation": [ { "name": "Service de Psychiatrie et Addictologie de l’adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France" }, { "name": "Department of Psychobiology and Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, F-28223 Madrid, Spain" }, { "name": "Department of Biological and Health Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, F-28049 Madrid, Spain" } ], "authenticated-orcid": false, "family": "Delgado-Álvarez", "given": "Alfonso", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-8096-3987", "affiliation": [ { "name": "Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany" } ], "authenticated-orcid": false, "family": "Kornhuber", "given": "Johannes", "sequence": "additional" }, { "affiliation": [ { "name": "Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany" } ], "family": "Gulbins", "given": "Erich", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Psychiatry, New York State Psychiatric Institute/Columbia University, New York, NY 10032, USA" } ], "family": "Olfson", "given": "Mark", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-3587-7182", "affiliation": [ { "name": "Service de Psychiatrie de l’Adulte, DMU Psychiatrie et Addictologie, Hôpital Hôtel-Dieu, AP-HP, Université Paris Cité, F-75004 Paris, France" } ], "authenticated-orcid": false, "family": "Ouazana-Vedrines", "given": "Charles", "sequence": "additional" }, { "affiliation": [ { "name": "Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany" }, { "name": "Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany" } ], "family": "Carpinteiro", "given": "Alexander", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6795-5448", "affiliation": [ { "name": "Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France" } ], "authenticated-orcid": false, "family": "Cougoule", "given": "Céline", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6317-7298", "affiliation": [ { "name": "Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany" } ], "authenticated-orcid": false, "family": "Becker", "given": "Katrin Anne", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-4780-0147", "affiliation": [ { "name": "Department of Psychobiology and Behavioural Sciences Methods, Faculty of Psychology, Universidad Complutense de Madrid, F-28223 Madrid, Spain" } ], "authenticated-orcid": false, "family": "Alvarado", "given": "Jesús M.", "sequence": "additional" }, { "affiliation": [ { "name": "INSERM U1266, Université Paris Cité, F-75014 Paris, France" }, { "name": "Service de Psychiatrie et Addictologie de l’adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France" } ], "family": "Limosin", "given": "Frédéric", "sequence": "additional" }, { "affiliation": [], "name": "on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium", "sequence": "additional" } ], "container-title": "Pharmaceuticals", "container-title-short": "Pharmaceuticals", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 8, 4 ] ], "date-time": "2023-08-04T13:27:48Z", "timestamp": 1691155668000 }, "deposited": { "date-parts": [ [ 2023, 8, 4 ] ], "date-time": "2023-08-04T14:46:15Z", "timestamp": 1691160375000 }, "indexed": { "date-parts": [ [ 2023, 8, 5 ] ], "date-time": "2023-08-05T04:24:25Z", "timestamp": 1691209465597 }, "is-referenced-by-count": 0, "issue": "8", "issued": { "date-parts": [ [ 2023, 8, 4 ] ] }, "journal-issue": { "issue": "8", "published-online": { "date-parts": [ [ 2023, 8 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 8, 4 ] ], "date-time": "2023-08-04T00:00:00Z", "timestamp": 1691107200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1424-8247/16/8/1107/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "1107", "prefix": "10.3390", "published": { "date-parts": [ [ 2023, 8, 4 ] ] }, "published-online": { "date-parts": [ [ 2023, 8, 4 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1016/j.encep.2020.04.005", "article-title": "Ensuring Mental Health Care during the SARS-CoV-2 Epidemic in France: A Narrative Review", "author": "Chevance", "doi-asserted-by": "crossref", "first-page": "193", "journal-title": "L’Encephale", "key": "ref_1", "volume": "46", "year": "2020" }, { "DOI": "10.1038/s41591-020-1001-6", "article-title": "A Stochastic Agent-Based Model of the SARS-CoV-2 Epidemic in France", "author": "Hoertel", "doi-asserted-by": "crossref", "first-page": "1417", 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