Overview: A nasal spray with antiviral potential
A recent Phase 2 randomized clinical trial explored whether azelastine nasal spray could reduce infections with SARS-CoV-2, the virus behind COVID-19, and rhinovirus, a common cause of the cold. Conducted at a single center and funded by the spray’s manufacturer, the study enrolled 450 adults and compared 0.1% azelastine nasal spray used three times daily for eight weeks against a placebo. While the findings are encouraging, experts caution that the study’s design limits broad generalizations to diverse populations.
The antiviral rationale for azelastine
Azelastine is a well-known nasal antihistamine primarily used to treat allergic rhinitis. Laboratory research has suggested several mechanisms that could underlie antiviral effects in the airway: interaction with the ACE2 receptor, inhibition of the SARS-CoV-2 main protease (Mpro), and modulation of receptors like σ-1. Some studies have also linked azelastine to reduced expression of intercellular adhesion molecule 1 (ICAM-1), which may influence viral entry and replication. Early clinical signals have hinted that azelastine could lower viral loads in infected individuals, prompting investigation of its preventive potential in exposed people.
The study design and what was measured
Participants had a mean age of about 33 years and were predominantly female and White. Most had received COVID-19 vaccination, with a median of three doses; many vaccinations were given more than a year prior to enrollment. Importantly, the trial used a higher-than-usual dose for allergy care: 0.1% azelastine administered three times daily for eight weeks, rather than the typical twice-daily schedule for allergic rhinitis.
Infection surveillance relied on twice-weekly rapid antigen testing, followed by PCR confirmation for positive results. When participants showed respiratory symptoms but tested negative on RATs, PCR testing for SARS-CoV-2 and other respiratory viruses was also performed. The trial thus aimed to capture a broad spectrum of respiratory infections, with a particular focus on DNA or RNA-based confirmation of infection status.
Key findings: reduced infection rates and delayed onset
The azelastine group had notably lower infection rates compared with placebo: 2% versus 6.7% for SARS-CoV-2, signaling about a 70% relative reduction in infection risk. The onset of infection was also delayed by roughly 12 days in the azelastine group, suggesting a protective effect during periods of exposure. Among those who did contract COVID-19, symptomatic infections were less common in the azelastine arm, and the duration of detectable infection, as measured by RAT, was shorter by about 1.7 days on average.
Beyond COVID-19, rhinovirus infections were less frequent among azelastine recipients (2% vs 6%), indicating potential broader antiviral activity. When considering all PCR-confirmed respiratory infections, 9% occurred in the azelastine group compared with 22% in controls. Baseline immune status, inferred from prior SARS-CoV-2 antibodies, appeared to modestly influence reinfection risk.
Safety profile and practical considerations
Adverse events were similar in overall frequency between groups, though they were somewhat more likely to be labeled treatment-related in the azelastine group. Most adverse effects were mild and consistent with known nasal spray tolerability, including bitter taste, nosebleeds, and fatigue. The authors described the product as generally safe and easily accessible, presenting amply practical potential for pre-exposure prophylaxis in high-risk settings such as crowded events or travel.
Limitations and the path forward
Researchers stressed that the single-center design, modest sample size, and potential unblinding due to the distinctive bitter taste of azelastine limit how broadly the results can be applied. The placebo formulation might also offer some nasal barrier benefits. Consequently, larger, multicenter trials are essential to confirm these findings, determine the optimal dosing strategy, and assess efficacy against a wider range of populations and circulating viral variants.
What this means for the future of respiratory-virus prevention
If validated in future studies, azelastine nasal spray could become a convenient, over-the-counter option for pre-exposure protection against SARS-CoV-2 and rhinoviruses, especially in settings with high exposure risk. Its existing availability and familiar safety profile could accelerate adoption, pending robust evidence from diverse populations and longer follow-up. Researchers are actively pursuing multicenter trials to clarify the role of azelastine as a broader antiviral preventive strategy, potentially extending protection to other respiratory pathogens in due course.
Bottom line
The study offers promising signals that azelastine nasal spray may reduce SARS-CoV-2 and rhinovirus infections, delay infection onset, and shorten symptomatic viral periods. While encouraging, these results require confirmation in larger, more diverse trials before azelastine can be recommended as a standard preventive measure against respiratory viruses.
