Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study.

Marina Sánchez‐Rico ,Nicolas Hoertel,Elisa Salamanca,Raphaël Vernet,Mélodie Bernaux,Anita Burgun,Pedro De La Muela,Ali Bellamine,Antoine Neuraz,Mark Olfson,Nathanaël Beeker,Carlos Blanco,Alexandre Gramfort,Christel Daniel,Frédéric Limosin,Cédric Lemogne,Pierre Meneton,G Lemaître ,Nicolás Paris

doi:10.3390/jcm10245891

Abstract

(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.

Highlights

Global spread of the novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), has created an unprecedented infectious disease crisis worldwide [1,2,3,4]
We examined the association between hydroxyzine use at hospital admission and mortality among adult patients who have been admitted to these medical centers for COVID-19, while adjusting for potential confounders, including patients’ characteristics, medical conditions, and use of other medications
Of the 17,131 patients hospitalized for laboratory-confirmed COVID-19, 1963 patients

Summary

Introduction

Global spread of the novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), has created an unprecedented infectious disease crisis worldwide [1,2,3,4]. Antihistamines are widely used in the treatment of urticaria, allergic rhinitis, hay fever, conjunctivitis, and pruritus. They work by competitive binding to H1 receptors and inhibiting the action of histamine, a primary mediator of an early-phase allergic inflammatory response that modulates the late-phase response characterized by cellular influx of eosinophils, neutrophils, basophils, mononuclear cells, and T lymphocytes [9]. In vivo and in vitro studies have suggested additional anti-inflammatory properties of H1 antihistamines, including both receptor-dependent and receptor-independent mechanisms [10]. The receptor-independent mechanisms, which require higher drug concentrations, may include inhibition of the release of pre-formed mediators, such as histamine and eosinophil proteins, by inflammatory cells as well as eicosanoid generation and oxygen free radicals’ production [10]

Methods

Results

Conclusion