Nasal antihistamine spray cut risk of COVID-19 infection by about two-thirds in phase 2 trial
Phase 2 study in Germany found azelastine nasal spray lowered confirmed SARS‑CoV‑2 infection rates compared with placebo over 56 days
A phase 2 clinical trial conducted at Saarland University Hospital found that a commonly used antihistamine nasal spray, azelastine, significantly reduced the risk of confirmed SARS‑CoV‑2 infection compared with placebo, researchers reported.
The randomized trial enrolled 450 healthy adults between March 2023 and July 2024. Participants were assigned to self-administer either an azelastine nasal spray or a placebo three times per day for 56 days. SARS‑CoV‑2 rapid antigen testing was performed twice weekly to detect infections, and participants who reported symptoms but tested negative on antigen assays underwent additional PCR testing for respiratory viruses.
Among the 227 individuals who received the azelastine spray, 2.2% developed confirmed COVID‑19 during the study period, compared with 6.7% in the placebo group, the researchers reported in JAMA Internal Medicine. The difference represented a roughly two‑thirds reduction in confirmed infections in the active‑treatment arm during the 56‑day dosing window.
The trial used frequent surveillance testing to identify infections and applied PCR follow-up testing when symptoms and antigen results were discordant. The study authors described the findings as evidence that topical application of azelastine to the nasal mucosa may reduce or delay SARS‑CoV‑2 infection, but they characterized the work as a phase 2 investigation that requires confirmation.
Azelastine is an antihistamine formulation commonly prescribed for allergic rhinitis and available in nasal spray form. The study tested whether routine nasal application could alter viral acquisition at the site of early infection. The investigators randomized participants and monitored them prospectively over the two‑month treatment period; the trial was conducted after wide public availability of vaccines and antivirals, and during a period when multiple SARS‑CoV‑2 variants were circulating.
The authors noted the lower incidence of confirmed infection in the azelastine group relative to placebo but did not report long‑term outcomes beyond the 56‑day treatment window. As a phase 2 trial, the study was not designed to provide definitive evidence of population‑level effectiveness, and the researchers recommended larger, well‑powered phase 3 trials to evaluate efficacy, safety and durability of protection across diverse populations and variant settings.
If confirmed in larger trials, a readily available nasal spray could represent an additional, low‑cost tool to reduce risk of SARS‑CoV‑2 infection, particularly in settings where exposure risk is high or in individuals unable to mount strong vaccine responses. The researchers and independent experts cautioned that the findings do not replace established prevention measures such as vaccination, ventilation and masking when appropriate.
The trial's publication in JAMA Internal Medicine provides peer‑reviewed documentation of the results and methods; further clinical research will be needed to determine whether azelastine or related intranasal therapies can be integrated into public health recommendations for COVID‑19 prevention.