Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections

DOI record: { "DOI": "10.1001/jamainternmed.2025.4283", "ISSN": [ "2168-6106" ], "URL": "http://dx.doi.org/10.1001/jamainternmed.2025.4283", "abstract": "<jats:sec><jats:title>Importance</jats:title><jats:p>Limited pharmaceutical options exist for preexposure prophylaxis of COVID-19 beyond vaccination. Azelastine, an antihistamine nasal spray used for decades to treat allergic rhinitis, has in vitro antiviral activity against respiratory viruses, including SARS-CoV-2.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To determine the efficacy and safety of azelastine nasal spray for prevention of SARS-CoV-2 infections in healthy adults.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>A phase 2, double-blind, placebo-controlled, single-center trial was conducted from March 2023 to July 2024. Healthy adults from the general population were enrolled at the Saarland University Hospital in Germany.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Participants were randomly assigned 1:1 to receive azelastine, 0.1%, nasal spray or placebo 3 times daily for 56 days. SARS-CoV-2 rapid antigen testing (RAT) was conducted twice weekly, with positive results confirmed by polymerase chain reaction (PCR). Symptomatic participants with negative RAT results underwent multiplex PCR testing for respiratory viruses.</jats:p></jats:sec><jats:sec><jats:title>Main Outcome</jats:title><jats:p>The primary end point was the number of PCR-confirmed SARS-CoV-2 infections during the study.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 450 participants were randomized, with 227 assigned to azelastine and 223 to placebo; 299 (66.4%) were female, 151 (33.6%) male, with a mean (SD) age of 33.0 (13.3) years. Most were White (417 [92.7%]), with 4 (0.9%) African, 22 (4.9%) Asian, and 7 (1.6%) of other ethnicity. In the intention-to-treat (ITT) population, the incidence of PCR-confirmed SARS-CoV-2 infection was significantly lower in the azelastine group (n = 5 [2.2%]) compared with the placebo group (n = 15 [6.7%]) (OR, 0.31; 95% CI, 0.11-0.87). As secondary end points, azelastine demonstrated an increase in mean (SD) time to SARS-CoV-2 infection among infected participants (31.2 [9.3] vs 19.5 [14.8] days), a reduction of the overall number of PCR-confirmed symptomatic infections (21 of 227 participants vs 49 of 223 participants), and a lower incidence of PCR-confirmed rhinovirus infections (1.8% vs 6.3%). Adverse events were comparable between the groups.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>In this single-center trial, azelastine nasal spray was associated with reduced risk of SARS-CoV-2 respiratory infections. These findings support the potential of azelastine as a safe prophylactic approach warranting confirmation in larger, multicentric trials.</jats:p></jats:sec><jats:sec><jats:title>Trial registration</jats:title><jats:p>EudraCT number: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://drks.de/search/de/trial/DRKS00031059\">2022-003756-13</jats:ext-link></jats:p></jats:sec>", "author": [ { "affiliation": [ { "name": "Saarland University, Saarbruecken, Germany" } ], "family": "Lehr", "given": "Thorsten", "sequence": "first" }, { "affiliation": [ { "name": "Ursapharm Arzneimittel GmbH, Saarbruecken, Germany" } ], "family": "Meiser", "given": "Peter", "sequence": "additional" }, { "affiliation": [ { "name": "Saarland University, Saarbruecken, Germany" } ], "family": "Selzer", "given": "Dominik", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine V, Saarland University Medical Center, Germany" } ], 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