Introduction: A Promising Approach in Respiratory Virus Prevention
Azelastine nasal spray, long used to treat allergic rhinitis, is being explored as a potential preventive tool against respiratory viruses, including SARS-CoV-2. Recent findings from a phase II randomized trial published in JAMA Internal Medicine indicate that intranasal azelastine may lower the rate of SARS-CoV-2 infections and rhinovirus infections compared with placebo, offering a potential pre-exposure prophylaxis strategy in high-risk settings.
The antiviral rationale: How azelastine might work against coronaviruses
Laboratory studies have suggested several antiviral mechanisms for azelastine beyond its antihistamine action. These include interactions with the ACE2 receptor that SARS-CoV-2 uses to enter cells, inhibition of the viral main protease (Mpro), and modulation of receptors and molecules involved in viral entry and inflammation. In clinical contexts, azelastine has shown reduced viral load in some patients with COVID-19, hinting at a possible role in prevention as well as treatment.
Study design: A closer look at the phase II trial
The trial enrolled 450 participants in a single-center setting with a mean age in the early 30s. The majority were women and White, and most had received COVID-19 vaccination (a median of three shots). Eligible participants were randomized to receive 0.1% azelastine nasal spray or a placebo, three times daily for eight weeks—an dosing regimen higher than typical allergic rhinitis use. Participants were tested for SARS-CoV-2 with rapid antigen tests twice weekly, with positive results confirmed by PCR. Symptomatic individuals with negative RAT results underwent additional PCR testing to capture other respiratory infections.
Key findings: Reduced infection rates and delayed onset
Compared with placebo, the azelastine group showed a notable reduction in SARS-CoV-2 infections: 2% vs 6.7%. This translates to roughly a 70% relative reduction in infection risk and a 12-day delay in time to infection for those using azelastine. Among those who contracted the virus, symptoms persisted for about 1.7 fewer days in the azelastine group, according to self-reported RAT results. The protective signal held even when exposure risk was higher, suggesting a robust effect against infection under the study conditions.
Rhinovirus infections, another common cause of winter illness, also decreased with azelastine: 2% in the treatment arm vs 6% in controls. Across all PCR-detected respiratory infections, 9% occurred in the azelastine group compared with 22% in the placebo group. These findings hint at a broader antiviral potential for azelastine beyond SARS-CoV-2.
Safety and limitations: What the trial shows—and what it doesn’t
Adverse events occurred at similar overall frequencies in both groups, though those on azelastine more frequently reported treatment-related effects such as a bitter taste, nosebleeds, and fatigue. Most adverse events were mild. The single-center design, relatively small sample size, and possible unblinding due to taste in the azelastine group limit how broadly these results can be applied. The placebo formulation itself might have contributed to some protective effects by stabilizing the nasal barrier, further complicating interpretation. Funding from the product manufacturer and its collaboration with university researchers also call for cautious extrapolation until larger, multicenter trials replicate findings.
Implications and next steps: Where this could lead
These results support the potential utility of azelastine as a safe, accessible option for pre-exposure prophylaxis against SARS-CoV-2, particularly in high-risk environments such as crowded events or travel. If confirmed in larger trials, azelastine could become a convenient adjunct to existing preventive measures, complementing vaccines and non-pharmaceutical interventions. Researchers stress the need for multicenter studies with diverse populations to validate effectiveness across different ages, ethnicities, and exposure settings, as well as exploration of its impact on other respiratory viruses beyond rhinovirus and SARS-CoV-2.
Bottom line: A promising lead requiring more evidence
While initial data are encouraging, azelastine nasal spray remains investigational for infection prevention. Its ease of use and favorable safety profile make it a compelling candidate for further study, but clinicians and public health officials should await confirmation from larger, multicenter trials before integrating azelastine into standard pre-exposure prophylaxis guidelines.
