What is Azelastine Nasal Spray and COVID-19 Prevention?

Review of a phase 2 clinical trial testing whether azelastine, an allergy nasal spray, can reduce SARS-CoV-2 infections.

Infectious Diseases

Azelastine Nasal Spray and COVID-19 Prevention

2025-09-16

Intro

Azelastine is a long-established antihistamine nasal spray, widely used for hay fever and allergic rhinitis. A phase 2 clinical trial published in JAMA Internal Medicine (September 2025) tested whether it could reduce SARS-CoV-2 infections. The results showed a modest but statistically significant reduction in infections — raising interest in repurposing an over-the-counter allergy spray for COVID-19 prevention.

Key Points

Trial of 450 healthy adults: 2.2% infections with azelastine vs 6.7% with placebo.
This equals about 5 fewer infections per 100 people treated.
Use was 3× daily for 56 days; higher dosing if exposed/symptomatic.
Side effects: bitter taste, nosebleeds, mild fatigue.
Industry-funded by the spray’s manufacturer (Ursapharm).
Results are promising but preliminary; larger independent trials are needed.

Background

Azelastine is a second-generation antihistamine, normally marketed for allergic rhinitis. In laboratory studies, it has shown antiviral activity against SARS-CoV-2, rhinovirus, and other respiratory viruses. Researchers designed the CONTAIN trial to test its role in pre-exposure prophylaxis against COVID-19.

Trial Findings

Primary outcome: SARS-CoV-2 infection confirmed by PCR.
Results: Azelastine 5/227 vs placebo 15/223. Odds ratio 0.31, P = 0.02.
Secondary outcomes: fewer symptomatic infections, longer time to infection, fewer rhinovirus cases.
Limitations: single center, modest sample size, mostly young vaccinated participants, industry sponsorship.

Risks and Safety

Azelastine’s safety profile was consistent with known use in allergies. Mild side effects were more frequent than placebo but no serious treatment-related harms occurred. Continuous long-term use for infection prevention has not been tested.

Off-Label Use

Azelastine is not licensed for COVID-19 prevention. Any use in this setting is experimental. The trial explored both prevention and early treatment strategies, raising questions about how such a product might be used outside controlled studies.

FAQ

Q: Is this a miracle spray?
A: No. The benefit was modest — preventing about 5 infections per 100 people.

Q: Should I start using it now?
A: No health authority currently recommends azelastine for COVID-19 prevention. More evidence is needed.

Q: What about other respiratory viruses?
A: The trial suggested fewer rhinovirus infections, but larger studies are required.