A recent study published in JAMA Internal Medicine suggests that azelastine nasal spray may significantly lower the risk of SARS-CoV-2 infection. The single center, phase 2 randomized controlled trial enrolled 450 participants, predominantly White women with an average age of 33 years, to evaluate the effect of 0.1% azelastine nasal spray compared with a placebo.
Azelastine, a selective histamine H1 receptor antagonist with some H2 receptor activity, is commonly used to relieve allergy symptoms such as itching, sneezing, and nasal congestion. In this study, participants received the nasal spray or placebo three times daily for 8 weeks, which is a higher frequency than the usual twice daily dose recommended for moderate to severe allergic rhinitis. SARS-CoV-2 screening was performed twice weekly using rapid antigen tests, with positive results confirmed by PCR. Symptomatic participants who tested negative were also assessed using PCR for SARS-CoV-2 and other respiratory viruses.
The results showed that only 2% of participants in the azelastine group contracted SARS-CoV-2, compared with 6.7% in the placebo group, indicating an approximate 70% reduction in infection risk. Azelastine also delayed infection onset by 12 days, reduced the likelihood of symptomatic COVID-19, and shortened the duration of positive test results by an average of 1.7 days. Rhinovirus was the most common non-COVID infection, and azelastine treatment lowered infection rates to 2% versus 6% in the placebo group. Overall, PCR-confirmed respiratory infections occurred in 9% of the azelastine group compared with 22% of controls. Participants with pre-existing SARS-CoV-2 antibodies had slightly lower reinfection odds, suggesting modest effects of baseline immunity.
Adverse events were comparable between groups, though those in the azelastine group were more often considered treatment related. Most were mild, including bitter taste, nosebleeds, and fatigue. Supporting these findings, a separate study indicated that azelastine may have broad antiviral activity and is safe for the local prevention and treatment of common respiratory viral infections via nasal administration. The study highlights azelastine’s potential to protect against symptomatic rhinovirus, possibly through ICAM-1 inhibition.
While the nasal spray is convenient and accessible for pre-exposure SARS-CoV-2 prevention, the single center design, small sample size, and potential for unblinding limit the general applicability of the findings. Experts caution that most nasal sprays for COVID-19 remain under clinical investigation and have not yet received widespread regulatory approval. They are being explored primarily as adjuncts to existing preventive measures such as vaccination and mask wearing, rather than as replacements. Individuals should consult healthcare professionals before using any nasal spray for COVID-19 prevention or treatment, especially those with underlying health conditions.
Azelastine nasal spray shows promising potential in reducing SARS-CoV-2 infection risk and other respiratory viral infections, offering a convenient additional preventive option. While the findings are encouraging, larger multicenter trials are needed to confirm its efficacy, safety, and broader applicability. Nasal sprays should complement, not replace, established preventive measures such as vaccination, mask wearing, and hygiene practices, and individuals should consult healthcare professionals before use.
References
- Lehr, T., Meiser, P., Selzer, D., et al. (2025). Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial. JAMA Internal Medicine. doi:10.1001/jamainternmed.2025.4283.
- Azelastine [Internet]. [cited 2025 Oct 8]. Available from: https://go.drugbank.com/drugs/DB00972
- Fischhuber K, Bánki Z, Kimpel J, Kragl N, Rössler A, Bolze A, Muellauer B, Angerer J, Nagy G, Nagy E, Szijarto V. Antiviral Potential of Azelastine against Major Respiratory Viruses. Viruses. 2023 Nov 23;15(12):2300. doi: 10.3390/v15122300. PMID: 38140540; PMCID: PMC10747764.