A common over-the-counter allergy nasal spray containing azelastine (sold as Astepro, Astelin) appeared to lower the risk of SARS-CoV-2 infection and other respiratory viruses in a phase 2, double-blind, placebo-controlled trial published Sept. 2 in JAMA Internal Medicine.
Study design and participants
Researchers at Saarland University Hospital in Germany enrolled 450 healthy adults aged 18 to 65 between March 2023 and July 2024. Most participants were female (66%), identified as white (93%), and had received at least one COVID-19 vaccine dose (median three doses). None had signs of acute infection at enrollment. Participants were randomized to receive either azelastine 0.1% nasal spray (1 mg/mL azelastine hydrochloride) or an identical-looking placebo. Both sprays contained the same inactive ingredients (hypromellose, sodium chloride, purified water). The routine dose was one puff into each nostril three times daily for 56 days; dosing increased to five times daily for three days if symptoms developed or after a known exposure.
Testing and outcomes
Trained staff administered SARS-CoV-2 rapid antigen tests twice weekly; positive rapid tests were confirmed with PCR. Symptomatic participants with negative rapid antigen tests underwent multiplex PCR screening for other respiratory viruses. The primary outcome was PCR-confirmed COVID-19 during the 56-day treatment period. Secondary outcomes included symptomatic COVID-19, time to infection, duration of positive rapid tests, incidence of other respiratory infections, and safety events.
Key results
– PCR-confirmed COVID-19 occurred in 2.2% of azelastine users versus 6.7% of placebo users, corresponding to an approximate 69% relative risk reduction.
– Average time to infection was longer in the azelastine group (31 days) than placebo (19 days).
– Duration of positive rapid antigen tests averaged 3.4 days with azelastine versus 5.1 days with placebo.
– Rhinovirus (common cold) was detected in 1.8% of azelastine users versus 6.3% of placebo users, roughly a 71% lower risk.
– Any laboratory-confirmed respiratory infection occurred in 8.4% of the azelastine group compared with 18.8% of the placebo group.
Safety
Side effects were generally mild and consistent with known azelastine effects. A bitter taste was reported by 9.3% of azelastine users versus 1.3% of placebo users. Nosebleeds occurred in 6.6% of azelastine users and 4% of placebo users. Tiredness and dizziness were noted as possible effects. Serious adverse events were rare and none were judged related to the spray; no deaths occurred.
Expert guidance and practical considerations
Clinicians advising patients noted a few practical cautions. Parth Bhavsar, MD, highlighted that azelastine can cause dizziness and recommended avoiding alcohol or sedatives while using it and exercising caution when driving or operating machinery. He also pointed out that azelastine does not cause rebound congestion like topical decongestant sprays, but that dose-dependent drowsiness, local nasal burning, or nosebleeds are practical risks with prolonged or more frequent use. People with recurrent epistaxis or recent nasal surgery should consult a physician before use.
Steven Goldberg, MD, MBA, advised that anyone with a known hypersensitivity to azelastine or any spray ingredient should avoid it, and that safety data are limited for pregnant or breastfeeding people. He suggested following label instructions for over-the-counter azelastine HCl 0.1% or 0.15% (typically once or twice daily) and considering short-term use in high-exposure situations, during travel, or at early symptom onset. Patients with underlying health concerns or those considering longer-term use should consult their doctor.
Limitations
The authors noted several limitations: the trial was relatively small, conducted at a single site, and enrolled a predominantly white population, so results may not generalize to more diverse groups. Larger, multicenter trials will be needed to confirm these findings and better define optimal dosing, duration, and effectiveness across different populations and circulating virus variants.
Public health perspective
Investigators and experts emphasize that while azelastine nasal spray showed early promise for reducing the incidence of some respiratory infections and shortening detectable viral shedding, it should be viewed as a complementary tool—not a replacement for COVID-19 vaccination, testing, masking where appropriate, or other public health measures. Anyone considering off-label or frequent use should discuss it with their healthcare provider.