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

{ 'indexed': {'date-parts': [[2023, 8, 5]], 'date-time': '2023-08-05T04:24:25Z', 'timestamp': 1691209465597}, 'reference-count': 78, 'publisher': 'MDPI AG', 'issue': '8', 'license': [ { 'start': { 'date-parts': [[2023, 8, 4]], 'date-time': '2023-08-04T00:00:00Z', 'timestamp': 1691107200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, '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>', 'DOI': '10.3390/ph16081107', 'type': 'journal-article', 'created': {'date-parts': [[2023, 8, 4]], 'date-time': '2023-08-04T13:27:48Z', 'timestamp': 1691155668000}, 'page': '1107', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among ' 'Patients with SARS-CoV-2: An Observational Study', 'prefix': '10.3390', 'volume': '16', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7890-1349', 'authenticated-orcid': False, 'given': 'Nicolas', 'family': 'Hoertel', 'sequence': 'first', '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'}]}, { 'given': 'Katayoun', 'family': 'Rezaei', 'sequence': 'additional', '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'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1121-8641', 'authenticated-orcid': False, 'given': 'Marina', 'family': 'Sánchez-Rico', 'sequence': 'additional', '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'}]}, { 'ORCID': 'http://orcid.org/0000-0002-1889-4503', 'authenticated-orcid': False, 'given': 'Alfonso', 'family': 'Delgado-Álvarez', 'sequence': 'additional', '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'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8096-3987', 'authenticated-orcid': False, 'given': 'Johannes', 'family': 'Kornhuber', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Psychiatry and Psychotherapy, University Hospital, ' 'Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), ' '91054 Erlangen, Germany'}]}, { 'given': 'Erich', 'family': 'Gulbins', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute of Molecular Biology, University Hospital Essen, ' 'University of Duisburg-Essen, 47057 Essen, Germany'}]}, { 'given': 'Mark', 'family': 'Olfson', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Psychiatry, New York State Psychiatric ' 'Institute/Columbia University, New York, NY 10032, USA'}]}, { 'ORCID': 'http://orcid.org/0000-0002-3587-7182', 'authenticated-orcid': False, 'given': 'Charles', 'family': 'Ouazana-Vedrines', 'sequence': 'additional', 'affiliation': [ { 'name': 'Service de Psychiatrie de l’Adulte, DMU Psychiatrie et ' 'Addictologie, Hôpital Hôtel-Dieu, AP-HP, Université Paris Cité, ' 'F-75004 Paris, France'}]}, { 'given': 'Alexander', 'family': 'Carpinteiro', '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'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6795-5448', 'authenticated-orcid': False, 'given': 'Céline', 'family': 'Cougoule', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute of Pharmacology and Structural Biology (IPBS), ' 'University of Toulouse, CNRS, 31000 Toulouse, France'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6317-7298', 'authenticated-orcid': False, 'given': 'Katrin Anne', 'family': 'Becker', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institute of Molecular Biology, University Hospital Essen, ' 'University of Duisburg-Essen, 47057 Essen, Germany'}]}, { 'ORCID': 'http://orcid.org/0000-0003-4780-0147', 'authenticated-orcid': False, 'given': 'Jesús M.', 'family': 'Alvarado', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Psychobiology and Behavioural Sciences Methods, ' 'Faculty of Psychology, Universidad Complutense de Madrid, ' 'F-28223 Madrid, Spain'}]}, { 'given': 'Frédéric', 'family': 'Limosin', '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'}]}, { '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', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2023, 8, 4]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '193', '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', 'volume': '46', 'author': 'Chevance', 'year': '2020', 'journal-title': 'L’Encephale'}, { 'key': 'ref_2', 'doi-asserted-by': 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