Inferring a causal relationship between ceramide levels and COVID-19 respiratory distress

Khodadoust, Mehran M.

doi:10.1038/s41598-021-00286-7

Cited by 27 publications

(36 citation statements)

References 28 publications

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“…b Models were adjusted for sex, age, race and ethnicity, obesity, number of diagnoses, history of mood or anxiety disorder, history of other psychiatric disorders, number of home medications, concurrent exposure to benzodiazepine or Z drug, concurrent exposure to antipsychotic drugs, and concurrent exposure to non-antidepressant drugs with FIASMA or S1R activity (listed in Table S1). markers [42][43][44][45], lending further support for FIASMA as an explanatory mechanism behind the associations reported in observational studies.…”

Section: Discussionsupporting

confidence: 55%

Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

et al. 2022

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Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive SARS-CoV-2 test performed in a non-hospital setting. Logistic regression analyses tested associations between home use of antidepressant medications and a composite outcome of ED visitation or hospital admission within 30 days. Secondary exposures included individual antidepressants and antidepressants with functional inhibition of acid sphingomyelinase (FIASMA) activity. Patients with antidepressant exposure were less likely to experience the primary composite outcome compared to patients without antidepressant exposure (adjusted odds ratio [aOR] 0.89, 95% CI 0.79–0.99, p = 0.04). This association was only observed with daily doses of at least 20 mg fluoxetine-equivalent (aOR 0.87, 95% CI 0.77–0.99, p = 0.04), but not with daily doses lower than 20 mg fluoxetine-equivalent (aOR 0.94, 95% CI 0.80–1.11, p = 0.48). In exploratory secondary analyses, the outcome incidence was also reduced with exposure to selective serotonin reuptake inhibitors (aOR 0.87, 95% CI 0.75–0.99, p = 0.04), bupropion (aOR 0.70, 95% CI 0.55–0.90, p = 0.005), and FIASMA antidepressant drugs (aOR 0.87, 95% CI 0.77–0.99, p = 0.03). Antidepressant exposure was associated with a reduced incidence of emergency department visitation or hospital admission among SARS-CoV-2 positive patients, in a dose-dependent manner. These data support the FIASMA model of antidepressants’ effects against COVID-19.

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Section: Discussionsupporting

confidence: 55%

Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

et al. 2022

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“…Instead, Bizkarguenaga et al [ 57 ] found by NMR that recovered COVID-19 patients between 3 and 10 months after diagnosis showed increased plasma levels of cholesterol, triglycerides (TG), and phospholipids. Finally, Khodadoust [ 58 ], through lipidomic analysis of 52 plasma samples, detected lipids belonging to the ceramide class increased by a 400-fold in infected patients.…”

Section: Metabolomics Of Covid-19mentioning

confidence: 99%

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Costanzo

Caterino

Fedele

et al. 2022

IJMS

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Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale to understand the pathobiology of the SARS-CoV-2 infection and its replication into human cells. The application of omics techniques has been addressed to every level of application, from the detection of mutations, methods of diagnosis or monitoring, drug target discovery, and vaccine generation, to the basic definition of the pathophysiological processes and the biochemical mechanisms behind the infection and spread of SARS-CoV-2. Thus, the term COVIDomics wants to include those efforts provided by omics-scale investigations with application to the current COVID-19 research. This review summarizes the diverse pieces of knowledge acquired with the application of COVIDomics techniques, with the main focus on proteomics and metabolomics studies, in order to capture a common signature in terms of proteins, metabolites, and pathways dysregulated in COVID-19 disease. Exploring the multiomics perspective and the concurrent data integration may provide new suitable therapeutic solutions to combat the COVID-19 pandemic.

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“… 2 Three studies found that plasma ceramide levels strongly correlate with clinical and inflammation severity among patients with COVID-19. 39 – 41 Intriguingly, SARS-CoV-2 infection was demonstrated to stimulate even this ASM/ceramide system. 2 Thus, an inhibition of sphingomyelin break down by the aforementioned special weakly basic drugs, so-called functional inhibitors of acid sphingomyelinase (FIASMAs), might by a promising approach to prevent SARS-CoV-2 entry into cells.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

Bonnet

Juckel

2022

J Clin Psychopharmacol

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Purpose/BackgroundStudies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2–infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.Methods/ProceduresWe conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.Finding/ResultsAs of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19–related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.Implications/ConclusionsAt present, the best evidence of an “anti–COVID-19” potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute “dark zones” in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

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Inferring a causal relationship between ceramide levels and COVID-19 respiratory distress

Cited by 27 publications

References 28 publications

Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

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