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J Clin Med ; 10(24)2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1572535


(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients' characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29-0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

Clin Pharmacol Ther ; 110(6): 1498-1511, 2021 12.
Article in English | MEDLINE | ID: covidwho-1245382


Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

COVID-19/enzymology , COVID-19/mortality , Hospitalization/trends , Intubation, Intratracheal/mortality , Intubation, Intratracheal/trends , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19 Testing/trends , Cohort Studies , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Sphingomyelin Phosphodiesterase/metabolism , Young Adult