A common over-the-counter nasal spray used for seasonal allergies has demonstrated significant potential in preventing COVID-19 infections, according to results from a randomized clinical trial published in JAMA Internal Medicine. The study, conducted by German scientists at Saarland University Hospital, found that participants using azelastine nasal spray experienced a three-fold reduction in COVID-19 infections compared to those receiving a placebo.
Clinical Trial Results
The randomized, double-blind phase 2 study, known as "CONTAIN," recruited 450 adults, mostly in their early 30s, and divided them into two groups over a 56-day observation period. The treatment group of 227 participants used azelastine nasal spray three times daily, while the control group of 223 individuals received a placebo spray with the same dosing regimen.
"During the observation period, 2.2% of the participants in the azelastine group became infected with SARS-CoV-2; in the placebo group, it was 6.7%—three times as many," said Professor Robert Bals, Director of the Department of Internal Medicine V at Saarland University Medical Center and the study's senior author. All participants underwent COVID rapid tests twice weekly, with infections confirmed by PCR testing.
Broader Antiviral Effects
Beyond COVID-19 prevention, the trial revealed additional protective benefits. The azelastine group showed fewer symptomatic SARS-CoV-2 infections and a lower overall number of confirmed respiratory infections. Notably, the treatment group also experienced significantly reduced rhinovirus infections, with only 1.8% developing rhinovirus compared to 6.3% in the placebo group.
These findings align with previous in vitro studies suggesting azelastine's antiviral effects against SARS-CoV-2 and other respiratory viruses. "This clinical trial is the first to demonstrate a protective effect in a real-world setting," Bals noted.
Proposed Mechanisms of Action
While researchers acknowledge uncertainty about azelastine's exact mechanism of action against COVID-19, they propose several possibilities. The antihistamine may bind to viruses in the nasal mucosa—the moist membrane lining the nose that pathogens must navigate to enter the body—and inhibit a key enzyme used for viral replication.
Another potential mechanism involves azelastine's interaction with the ACE2 receptor, the preferred entry point for SARS-CoV-2 into human cells, potentially preventing the virus from latching on and establishing infection.
Clinical Implications and Limitations
The researchers suggest practical applications for their findings. "Azelastine nasal spray could provide an additional easily accessible prophylactic to complement existing protective measures, especially for vulnerable groups, during periods of high infection rates, or before travelling," Bals explained.
However, the study had notable limitations. The participant population consisted primarily of young, relatively healthy adults, raising questions about effectiveness in higher-risk groups. Bals emphasized that azelastine should not replace vaccinations and stressed the need for larger studies before recommending it as routine prevention for the general public, particularly vulnerable populations.
Expert Perspectives
External experts provided measured responses to the findings. Dr. William Messer, associate professor of molecular microbiology and immunology at Oregon Health & Science University, described the results as "reasonably convincing" for risk reduction but questioned the practicality of the intensive three-times-daily regimen compared to mask-wearing.
Dr. Peter Chin-Hong, professor in the UCSF Health Division of Infectious Diseases, suggested azelastine could serve as an additional tool for people already using the spray for seasonal allergies but felt insufficient evidence exists for broader endorsement. "While promising, I don't think it's prime time to recommend this to block transmission," he stated, emphasizing continued vaccine prioritization for those 65 and older.
Future Research Directions
The trial results have broader implications for respiratory virus prevention strategies. Chin-Hong noted that the findings provide further evidence that nasal mucosa could be a vital target for future vaccines against COVID-19 and other respiratory viruses.
"The current COVID vaccines clearly do not do a great job of protecting against infections," he observed. "We need more mucosal vaccines for respiratory viruses. There's one which is widely used for influenza, and there's been ongoing work in mucosal vaccines for coronaviruses, but we need to continue to advocate for federal prioritization and support of these initiatives."
Bals emphasized the importance of continued research: "Our results highlight the need for larger, multicentre trials to continue exploring the use of azelastine nasal sprays as an on-demand preventive treatment, and to examine its potential effectiveness against other respiratory pathogens."
The study represents a collaboration between Saarland University Medical Center, the Institute of Clinical Pharmacy, the Institute of Virology, the Helmholtz Institute for Pharmaceutical Research Saarland, and pharmaceutical company URSAPHARM Arzneimittel GmbH, which sponsored the research and manufactured the investigational product.
