In a phase 2 randomized, double-blind trial of 450 healthy adult participants, over-the-counter azelastine 0.1% nasal spray was associated with fewer polymerase chain reaction–confirmed SARS-CoV-2 infections over 56 days compared with placebo (2% vs 7%).

Participants used one puff per nostril three times daily. Twice-weekly rapid antigen testing with polymerase chain reaction (PCR) confirmation was performed; symptomatic participants with a negative rapid antigen test received multiplex PCR for other respiratory pathogens. The protocol allowed use up to five times daily for three days after symptoms, confirmed infection, or high-risk exposure.

Symptomatic COVID-19 was 2% of the azelastine group vs 6% with placebo. Those receiving azelastine also reported fewer days of positivity and illness. Laboratory-confirmed respiratory infections overall were lower with azelastine, with 21 events vs 49 events. The proportion of participants who had at least one such event was 8% vs 19%.

Azelastine shows in-vitro antiviral activity. Proposed actions include interaction with ACE2, inhibition of SARS-CoV-2 protease Mpro, sigma-1 receptor modulation, and suppression of ICAM-1 upregulation. These are putative mechanisms and not proven mediators of clinical effect.

Adverse events were similar overall between groups. Bitter taste and nosebleeds were more frequent with azelastine, while serious adverse events were uncommon and not treatment-related.

Limitations included the single-center design, few primary COVID-19 events, a highly vaccinated and largely healthy cohort, potential taste-related unblinding, and symptom-triggered testing for non–SARS-CoV-2 pathogens that may have missed asymptomatic cases.

The study authors reported disclosures in the publication.

Source: JAMA Internal Medicine