BACKGROUND AND PURPOSE:

• Azelastine is an antihistamine nasal spray that has shown antiviral activity against respiratory viruses, including SARS-CoV-2
• Lehr et al. (JAMA Internal Medicine, 2025) assessed the efficacy and safety of azelastine nasal spray for prevention of SARS-CoV-2 infections in healthy adults

METHODS:

• Double-blind, placebo-controlled, single-center trial
  • CONTAIN study
  • Conducted in the state of Saarland, Germany
  • From March 2023
• Participants
  • 18 to 65 years
  • Healthy adults from the general population
• Interventions
  • Azelastine: 0.1%, nasal spray, 3 times daily for 56 days | If developed acute symptoms, confirmed SARS-CoV-2 infection of knowledge of contact with infected person then5 times daily over 3 days
  • Placebo
• Study design
  • SARS-CoV-2 rapid antigen testing (RAT) was conducted twice weekly
    • Positive results were confirmed with PCR testing
  • Patients who were symptomatic but had a negative RAT test underwent multiplex PCR for respiratory viruses
  • Analysis was by intention to treat
• Primary outcome
  • PCR-confirmed SARS-CoV-2 infections

RESULTS:

• Azelastine: 227 participants | Placebo: 223
  • Female: 66.4% | Mean age: 33.0 (SD, 13.3) years
  • White: 92.7% | African: 0.9% | Asian: 4.9% | Other: 1.6%
• The incidence of PCR-confirmed SARS-CoV-2 infection was significantly lower in the azelastine group
  • Azelastine: 2.2% | Placebo: 6.7%
  • Odds ratio (OR) 0.31 (95% CI, 0.11 to 0.87)
• Azelastine demonstrated an increase in mean time to SARS-CoV-2 infection among infected participants
  • Azelastine: 31.2 (SD, 9.3) days | Placebo: 19.5 (SD, 14.8) days
• Azelastine also reduced the overall number of PCR-confirmed symptomatic infections
  • Azelastine: 9.3% | Placebo: 22.0%
• Participants in the azelastine group also had lower incidence of PCR-confirmed rhinovirus infections
  • Azelastine: 1.8% | Placebo: 6.3%
• Adverse events were similar between the groups

CONCLUSION:

• Azelastine nasal spray was associated with a reduced incidence of SARS-CoV-2 infection
• The authors state

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

… larger trials are warranted to confirm efficacy against SARS-CoV-2 and to explore potential benefits against other respiratory pathogens across more diverse populations and settings

Learn More – Primary Sources:

Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial