Research Summary

Azelastine Nasal Spray Linked to Reduced Risk of SARS-CoV-2 Infection

Miranda Manier, BA

Key Highlights

  • Azelastine nasal spray significantly reduced the incidence of PCR-confirmed SARS-CoV-2 infections compared with placebo (2.2% vs 6.7%).
  • Secondary outcomes showed fewer symptomatic infections, longer time to infection, and reduced rhinovirus incidence in the azelastine group.
  • Adverse events were comparable between groups and aligned with known safety profiles of azelastine.
  • Findings suggest azelastine may serve as a safe, practical prophylactic option warranting further large-scale trials.

In a phase 2 randomized, double-blind, placebo-controlled trial, regular use of azelastine nasal spray was associated with a significantly lower incidence of SARS-CoV-2 infection. Among 450 participants, only 2.2% of those using azelastine developed laboratory-confirmed SARS-CoV-2 infection compared with 6.7% of those in the placebo group. Secondary analyses reinforced these findings, including fewer symptomatic cases, delayed time to infection, and reduced rhinovirus infections in the azelastine arm. Safety outcomes were consistent with the established tolerability of the medication.

The ongoing circulation of SARS-CoV-2, despite widespread vaccination and population immunity, highlights the need for additional prophylactic options. Although vaccines mitigate severe disease, infection rates remain high and continue to fuel postacute morbidity. Azelastine, a second-generation histamine H1-receptor antagonist long used for allergic rhinitis, has demonstrated antiviral properties in vitro against respiratory pathogens, including SARS-CoV-2. Previous studies have shown reduced viral load with azelastine in infected individuals, supporting its investigation as a preventive agent.

The trial enrolled healthy adults aged 18 to 65 years at Saarland University Hospital in Germany between March 2023 and July 2024. Participants were randomized 1:1 to receive azelastine 0.1% nasal spray or placebo, applied three times daily for 56 days. SARS-CoV-2 rapid antigen testing was conducted twice weekly, with confirmatory PCR testing for positive cases. Symptomatic individuals with negative antigen tests underwent multiplex PCR testing for respiratory pathogens. The primary endpoint was the incidence of PCR-confirmed SARS-CoV-2 infection.

Of the 450 participants randomized (mean age, 33 years; 66.4% female), infection rates were significantly lower in the azelastine group. Only 5 participants (2.2%) using azelastine developed infection compared with 15 (6.7%) in the placebo group, corresponding to an odds ratio of 0.31 (95% CI, 0.11-0.87). Azelastine use was also associated with longer time to SARS-CoV-2 infection (31.2 vs 19.5 days), fewer symptomatic infections (1.8% vs 6.3%), and reduced incidence of rhinovirus infections (1.8% vs 6.3%). Overall laboratory-confirmed respiratory infections occurred in 8.4% of azelastine participants compared with 18.8% of those receiving placebo.

Safety findings showed similar overall adverse event rates between groups. Events considered related to treatment were more frequent with azelastine, primarily reflecting known effects such as bitter taste, epistaxis, and mild tiredness. Serious adverse events were rare and not considered treatment-related.

The study has several limitations. As a single-center trial in a relatively young, healthy, and predominantly White population, generalizability may be limited. The modest sample size and low incidence of infections restricted statistical power for subgroup analyses. In addition, the bitter taste of azelastine may have partially unblinded participants, potentially biasing results.

“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.”

Reference:
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:e254283. doi:10.1001/jamainternmed.2025.4283