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

Hoertel et al., Pharmaceuticals, doi:10.3390/ph16081107
Aug 2023  
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Mortality, combined -7% Improvement Relative Risk Mortality, desloratadine 8% Mortality, hydroxyzine -9% Antihistamine H1RAs  Hoertel et al.  Prophylaxis Is prophylaxis with antihistamine H1RAs beneficial for COVID-19? Retrospective 5,772 patients in France (May 2020 - August 2022) No significant difference in mortality Hoertel et al., Pharmaceuticals, August 2023 Favorsantihistamine H1RA Favorscontrol 0 0.5 1 1.5 2+
12th treatment shown to reduce risk in January 2021
*, now with p = 0.000000021 from 13 studies.
Lower risk for mortality, recovery, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Retrospective 72,105 COVID+ hospitalized patients in France, showing no significant difference in mortality with antihistamine H1RAs desloratadine and hydroxyzine.
Study covers antihistamine H1RAs and fluvoxamine.
risk of death, 7.2% higher, HR 1.07, p = 0.50, treatment 962, control 4,810, adjusted per study, combined.
risk of death, 8.0% lower, HR 0.92, p = 0.81, treatment 11 of 94 (11.7%), control 62 of 470 (13.2%), NNT 67, adjusted per study, desloratadine, multivariable, Cox proportional hazards, day 28.
risk of death, 9.0% higher, HR 1.09, p = 0.40, treatment 104 of 962 (10.8%), control 591 of 4,810 (12.3%), adjusted per study, hydroxyzine, multivariable, Cox proportional hazards, day 28.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hoertel et al., 4 Aug 2023, retrospective, France, peer-reviewed, 14 authors, study period 2 May, 2020 - 31 August, 2022. Contact: (corresponding author),
This PaperH1RAsAll
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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': '', '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': '', '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': '', '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': '', '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': '', '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': '', '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': '', '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': '', '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': 'crossref', 'first-page': '1417', 'DOI': '10.1038/s41591-020-1001-6', 'article-title': 'A Stochastic Agent-Based Model of the SARS-CoV-2 Epidemic in France', 'volume': '26', 'author': 'Hoertel', 'year': '2020', 'journal-title': 'Nat. 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