Azelastine Nasal Spray Reduces Risk of SARS-CoV-2 Infection

New results from a phase 2 double-blind, placebo-controlled, single-center study published by investigators in JAMA Internal Medicine demonstrate that azelastine nasal spray (Astepro; Bayer) reduced the risk of SARS-CoV-2 respiratory infections, which cause the COVID-19 virus. The findings provide hope regarding the potential for a novel COVID-19 prevention method that is already commonly available and proven safe, though the results need confirmation in larger studies.¹

Azelastine is an antihistamine nasal spray that can treat symptoms of allergies. | Image Credit: © luchjschenF - stock.adobe.com

Promise of Azelastine in Infection Control

Azelastine, a second-generation histamine H1 receptor antagonist, is a standard over-the-counter nasal (OTC) spray used to treat patients with allergies. It offers temporary relief for nasal congestion, sneezing, and runny and itchy noses that can be caused by upper respiratory allergies. It was approved as an OTC product in 2021, making it the FDA’s first clearance of a steroid-free, antihistamine spray for the treatment of allergies. Its steroid-free composition and widespread availability for millions—the product is indicated for individuals aged 6 years and older—make it an intriguing option for further study in the context of prophylactic use.^2,3

Such research has found that azelastine carries antiviral activity against multiple respiratory viruses, including respiratory syncytial virus, influenza A, and SARS-CoV-2, bolstering the drug’s profile beyond its antiallergic properties. These effects are believed to include a series of innate mechanisms involving the angiotensin converting enzyme 2 and inhibition of the SARS-CoV-2 protease Mpro, according to investigators. Furthermore, randomized trials—often a hallmark of reliable trial data—have found that azelastine nasal spray can reduce SARS-CoV-2 viral load in patients with laboratory-confirmed infection.^1,4,5

Phase 2 Trial Finds Effectiveness of Azelastine in SARS-CoV-2 Prevention

The available evidence suggests that azelastine shows promise as a prophylactic intervention against SARS-CoV-2 and other pathogens. The current trial—the CONTAIN study—enrolled 450 healthy volunteers in Germany aged 18 through 65. Primarily, the authors sought to evaluate the development of SARS-CoV-2 infection through day 56 of the study. Volunteers were assigned to the following treatment groups: azelastine 0.1% nasal spray (227 participants) and placebo nasal spray (223 participants). Interestingly, a baseline analysis found that nearly all the participants were vaccinated at least once against COVID-19.¹

For the intention-to-treat population (ITT)—which included all randomized participants—the incidence of confirmed SARS-CoV-2 infection rate was meaningfully lower in the azelastine group (5 of 227 participants; 2.2%) compared with the placebo group (15 of 223 participants; 6.7%), totaling an odds ratio (OR) of 0.31 (95% CI, 0.11–0.87). The findings were corroborated by those from the per-protocol population, which included those with major study protocol deviations (n = 353). In this analysis, there was an OR of 0.36 (95% CI, 0.12–1.02), comparing favorably to the ITT cohort.¹

A series of secondary outcomes related to SARS-CoV-2 emphasized the primary observations. A time-to-event analysis indicated differences in infection rates between the azelastine and placebo groups, while the incidence of symptomatic SARS-CoV-2 infections was lower in patients using azelastine compared with placebo. Accordingly, there was a longer time to symptomatic COVID-19 infection in the azelastine group compared with the placebo group, and there was a shorter mean duration of SARS-CoV-2 positivity in the azelastine group.¹

Major Possible Implications for Clinical Practice

Critically, though the presence of other respiratory pathogens was observed, the number of overall infections was insignificant. In addition, there was a similar overall incidence of adverse events between the azelastine and placebo groups.¹

This data could serve as a paradigm shifter if confirmed in more extensive multicenter trials. With the possibility that azelastine could serve as prophylaxis for SARS-CoV-2, a new method for infection prevention could be widely available to patients. Given its popularity and common prescribing, pharmacists should be well-versed in its administration and be able to properly counsel patients on its application if further research solidifies its safety and effectiveness.¹

“The established safety profile, over-the-counter availability, and ease of use of azelastine nasal spray support its potential as a practical, scalable, on-demand approach to preexposure prophylaxis, particularly in high-risk settings such as large gatherings or travel,” the study authors concluded.¹

REFERENCES

1. Lehr T, Meiser P, Selzer D, et al. Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial. JAMA Intern Med. 2025. doi:10.1001/jamainternmed.2025.4283

2. PT Staff. FDA Approves New OTC Nasal Spray for Allergy Relief. Pharmacy Times. Published June 18, 2021. Accessed September 4, 2025. https://www.pharmacytimes.com/view/fda-approves-new-otc-nasal-spray-for-allergy-relief

3. Bernstein JA. Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007;10:2441-2452. doi:10.1185/030079907X226302

4. Klussman JP, Grosheva M, Meiser P, et al. Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients. Sci Reports. 2023;13:6839. doi:10.1038/s41598-023-32546-z

5. Meiser P, Flegel M, Holzer F, et al. Azelastine Nasal Spray in Non-Hospitalized Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial. Viruses. 2024;16(12):1914. doi:10.3390/v16121914