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0 0.5 1 1.5 2+ Mortality, FIASMA 20% Improvement Relative Risk Mortality, fluoxetine 51% FIASMA for COVID-19  Hoertel et al.  Prophylaxis Is prophylaxis with FIASMA medications beneficial for COVID-19? Retrospective 9,714 patients in France (May 2020 - August 2022) Lower mortality with FIASMA medications (p=0.000016) Hoertel et al., Pharmaceuticals, August 2023 Favors FIASMA Favors control

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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Retrospective 72,105 COVID+ hospitalized patients in France, showing lower mortality with FIASMA medications.
risk of death, 20.0% lower, HR 0.80, p < 0.001, treatment 625 of 4,857 (12.9%), control 772 of 4,857 (15.9%), NNT 33, day 28.
risk of death, 51.0% lower, HR 0.49, p = 0.04, treatment 9 of 145 (6.2%), control 100 of 725 (13.8%), NNT 13, adjusted per study, fluoxetine, multivariable, 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.
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Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study
Nicolas Hoertel, Katayoun Rezaei, Marina Sánchez-Rico, Alfonso Delgado-Álvarez, Johannes Kornhuber, Erich Gulbins, Mark Olfson, Charles Ouazana-Vedrines, Alexander Carpinteiro, Céline Cougoule, Katrin Anne Becker, Jesús M Alvarado, Frédéric Limosin
Pharmaceuticals, doi:10.3390/ph16081107
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 < 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.
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