COVID 19 has become a global health challenge even when the percentage of vaccinated individuals is large, and individuals have natural immunity against it due to involvement in previous infections. Vaccines are our best weapon, but researchers are scouting more methods to defend humanity, particularly of those who are more susceptible. A possible device might be a strange one; azelastine nasal spray, a drug that has been used to treat allergic rhinitis.
In September 2025, a new phase 2 randomized, placebo controlled clinical trial that indicated that regular administration of azelastine nasal spray has the ability to greatly reduce the risk of getting contracted with SARS-CoV-2, which is a virus causing COVID 19, was published in JAMA Internal Medicine.
What Is Azelastine?
Azelastine is a second generation antihistamine and is sold extensively over the counter as nasal spray. It has been used over decades to treat the symptoms of hay fever and other allergies. In addition to its effects as an antiallergic and anti inflammatory, laboratory experiments have demonstrated that azelastine has antiviral activity against various respiratory viruses such as SARS-CoV-2, influenza and rhinoviruses as well.
Scientists postulate that it operates in a number of ways:
Engagement with the ACE2 receptor which is the primary point of entry of SARS-CoV-2.
Blocking of the main protease of the virus (Mpro), which is essential in virus reproduction.
Manipulation of host immune pathways and an anti inflammatory effect.
Inhibition against an ICAM-1 receptor of rhinoviruses.
These results prompted researchers to conduct trials to determine whether azelastine would be a preventive measure of COVID 19.
The CONTAIN Clinical Trial
It was a randomized controlled trial (the CONTAIN study) carried out at Saarland University Hospital in Germany in March 2023 to July 2024.
Participants: 450 normal adults between 18-65 years, with no active infections.
Design: 1:1, randomized, placebo, double blind.
Intervention: Azelastine 0.1% nasal spray vs. placebo, but used thrice a day on 56 days.
Surveillance: Rapid antigen tests (with validation by PCR in case of a positive result) three times a week and further multiplex PCR among symptomatic persons.
This stringent design gave high confidence of accuracy in the determination of whether azelastine indeed lessened the risk of infection.
Key Findings
The results were striking:
COVID 19 Infections:Less than 2.2% of the participants in the azelastine group were PCR positive with SARS-CoV-2 as compared to 6.7% in the placebo group. This is a reduction of risk by 69 percent (odds ratio 0.31).
Symptomatic Infections: The symptomatic COVID 19 cases also were lower (1.8% vs. 6.3%).
Time to Infection: Infected persons taking azelastine had a longer time to remain virus free mean 31 days versus 19 days with the placebo group.
Other Viruses: Rhinovirus infections were also decreased (1.8% vs. 6.3%) by the spray, suggesting more general antiviral action.
Safety: Side effects were very mild and were typical of known azelastine use, such as bitter taste, and occasional nosebleeds. No treatment related serious adverse events were reported.
Why These Results Matter
The present research is notable due to the fact that there are only few safe and affordable preventive alternatives that are scalable. Although vaccines are still necessary, they can decrease over the period of time and differ in relation to new variants. Previously in use antibody therapies have mostly lost their activity against Omicron subvariants.
On the other: Azelastine nasal spray:
Is already sold over the counter in most countries.
Well developed safety profile.
Is simple and cheap to operate.
Demonstrates possible efficacy not only against SARS-CoV-2, but also against a variety of viruses.
Provided that these results are validated in large scale studies, azelastine would be a useful addition to the COVID 19 prevention toolkit, particularly in high risk environments such as in healthcare institutions, educational institutions, traveling, and big events.
Limitations of the Study
The trial was promising, but was limited:
Single center design only one hospital in Germany.
Small sample size 450 participants would not represent every variation in the population.
Vaccinated and mostly healthy people this may not necessarily be true even among older and immunocompromised individuals.
The possible unblinding of the bitter taste of azelastine might have identified the participants who were treated with the active spray.
Researchers emphasize that bigger multicentric research studies are required to validate efficacy in varied demographics and natural circumstances.
Broader Implications
Azelastine, in case proved effective, would be added to vaccines as a complementary protection method, i.e. vaccines to activate systemic immunity, and nasal sprays to prevent viruses at the point of contact.
The research paper also demonstrates a larger change of the way of thinking: instead of only looking at systemic treatments, topical nasal treatments can be of great importance in combating respiratory pandemics. Given that the nose is the main point of entry of SARS-CoV-2 and other respiratory pathogens, reinforcing this first line barrier may serve to decrease the number of infections and transmissions within the community.
Conclusion
The CONTAIN trial is a strong piece of evidence that azelastine nasal spray could be used to prevent new COVID 19 infections. Azelastine can improve prevention of the virus by preventing infections, prolonging time to infection, and preventing other viral infections like rhinovirus, and could be a safe, accessible and scalable preventative measure.
Although more studies are required, this over the counter allergy treatment is potentially a valuable addition to immunization, particularly in the case of risky populations and at times when the virus is more widespread.
As the world is still searching to find effective ways to help against COVID 19 and other respiratory viruses, azelastine nasal spray could be one of the most effective and the simplest additions to our arsenal of prevention measures.
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 Internal Medicine. Published online September 2, 2025.
https://jamanetwork.com/journals/jama/fullarticle/10.1001/jamainternmed.2025.4283