Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2023, 9, 20]], 'date-time': '2023-09-20T15:34:07Z', 'timestamp': 1695224047001}, 'posted': {'date-parts': [[2020, 10, 27]]}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'reference-count': 27, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2020, 10, 27]]}, 'abstract': '<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To ' 'examine the association between hydroxyzine use and mortality in patients hospitalized for ' 'COVID-19, based on its anti-inflammatory and antiviral ' 'properties.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Multicenter ' 'observational retrospective cohort ' 'study.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Greater Paris ' 'University hospitals, ' 'France.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>7,345 ' 'adults hospitalized for COVID-19 between 24 January and 1 April 2020, including 138 patients ' '(1.9%) who received hydroxyzine during the visit at a mean dose of 49.8 mg (SD=51.5) for an ' 'average of 22.4 days (SD=25.9).</jats:p></jats:sec><jats:sec><jats:title>Data ' 'source</jats:title><jats:p>Assistance Publique-Hôpitaux de Paris Health Data ' 'Warehouse.</jats:p></jats:sec><jats:sec><jats:title>Main outcome ' 'measures</jats:title><jats:p>The study endpoint was death. We compared this endpoint between ' 'patients who received hydroxyzine and those who did not in time-to-event analyses adjusting ' 'for patient characteristics (such as age, sex, and comorbidities), clinical and biological ' 'markers of disease’s severity, and use of other medications. The primary analysis was a ' 'multivariable Cox model with inverse probability weighting. Sensitivity analyses included a ' 'multivariable Cox model and a univariate Cox regression model in a matched analytic sample in ' 'a 1:1 ratio.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Over a mean ' 'follow-up of 20.3 days (SD=27.5), 994 patients (13.5%) had a primary end-point event. The ' 'primary multivariable analysis with inverse probability weighting showed a significant ' 'association between hydroxyzine use and reduced mortality (HR, 0.42; 95% CI, 0.25 to 0.71; ' 'p=0.001) with a significant dose-effect relationship (HR, 0.10; 95% CI, 0.02 to 0.45; ' 'p=0.003). This association was similar in sensitivity analyses. In secondary analyses ' 'conducted among subsamples of patients, we found a significant association between ' 'hydroxyzine use and a faster decrease in biological inflammatory markers associated with ' 'COVID-19-related mortality, including neutrophil-to-lymphocyte ratio (NLR), ' 'lymphocyte-to-C-reactive protein ratio (LCRP), and circulating interleukin 6 levels (IL-6) ' '(all p&lt;0.016), with a significant dose-effect relationship for NLR and LCRP (both ' 'p&lt;0.037).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In this ' 'retrospective observational study, hydroxyzine use was associated with reduced mortality in ' 'patients hospitalized for COVID-19. This association may be partially mediated by specific ' 'anti-inflammatory properties of H1 antihistamines. Double-blind controlled randomized ' 'clinical trials of hydroxyzine for COVID-19 are needed to confirm these ' 'results.</jats:p></jats:sec>', 'DOI': '10.1101/2020.10.23.20154302', 'type': 'posted-content', 'created': { 'date-parts': [[2020, 10, 27]], 'date-time': '2020-10-27T18:01:01Z', 'timestamp': 1603821661000}, 'source': 'Crossref', 'is-referenced-by-count': 8, 'title': 'Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for ' 'Coronavirus Disease 2019: Results from a multicenter observational study', 'prefix': '10.1101', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7890-1349', 'authenticated-orcid': False, 'given': 'Nicolas', 'family': 'Hoertel', 'sequence': 'first', 'affiliation': []}, {'given': 'Marina', 'family': 'Sánchez', 'sequence': 'additional', 'affiliation': []}, {'given': 'Raphaël', 'family': 'Vernet', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nathanaël', 'family': 'Beeker', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-7142-6728', 'authenticated-orcid': False, 'given': 'Antoine', 'family': 'Neuraz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Carlos', 'family': 'Blanco', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mark', 'family': 'Olfson', 'sequence': 'additional', 'affiliation': []}, {'given': 'Cédric', 'family': 'Lemogne', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pierre', 'family': 'Meneton', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christel', 'family': 'Daniel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nicolas', 'family': 'Paris', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alexandre', 'family': 'Gramfort', 'sequence': 'additional', 'affiliation': []}, {'given': 'Guillaume', 'family': 'Lemaitre', 'sequence': 'additional', 'affiliation': []}, {'given': 'Elisa', 'family': 'Salamanca', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mélodie', 'family': 'Bernaux', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ali', 'family': 'Bellamine', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anita', 'family': 'Burgun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Frédéric', 'family': 'Limosin', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2020103005500463000_2020.10.23.20154302v2.1', 'doi-asserted-by': 'crossref', 'unstructured': 'Hoertel N , Blachier M , Blanco C , et al. 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