Over the Counter Nasal Spray Shows Promising Results Against COVID-19 and Cold Infections

A new phase 2 clinical trial suggests that a widely available over-the-counter nasal spray typically used for allergies could offer a meaningful reduction in infection risk for both COVID-19 and other respiratory viruses. The antihistamine nasal spray azelastine demonstrated a significantly lower incidence of PCR-confirmed SARS-CoV-2 infections (the virus responsible for COVID-19), as well as fewer cases of common-cold-causing rhinovirus, compared with placebo.

The Study at a Glance

The trial, conducted at Saarland University Hospital in Germany and published in JAMA Internal Medicine, enrolled 450 healthy adults aged 18–65, most of whom had already received COVID-19 vaccination. Participants were randomly assigned to receive either azelastine 0.1% nasal spray (227 participants) or a placebo spray (223 participants) three times daily over a 56-day period. During this time, rapid antigen testing (twice weekly) and confirmatory PCR were used to detect SARS­-CoV-2 infections; symptomatic individuals with negative antigen tests underwent multiplex PCR for other respiratory viruses.

In the azelastine group, only 2.2 % (5 out of 227) developed PCR-confirmed COVID-19, compared to 6.7 % (15 out of 223) in the placebo group corresponding to roughly a 69% reduction in infection risk (odds ratio 0.31, 95% CI 0.11-0.87). As a secondary finding, the azelastine group also had a lower incidence of rhinovirus infection (1.8 % vs 6.3%) suggesting a 71% lower risk of common-cold infection in that subgroup.

Additionally, among those who did get infected, the azelastine group showed a longer time to infection (mean ~31 days vs ~19.5 in placebo) and a shorter duration of positive tests (average ~3.4 days vs ~5.1 days).

How Might It Work?

Although the study did not definitively establish the mechanism of action, several plausible biological explanations have been discussed:

• Azelastine has known antihistamine and anti-inflammatory properties (used for allergic rhinitis) and has also shown in vitro antiviral activity against respiratory viruses including SARS-CoV-2.
• By acting on the nasal mucosa (the primary site of viral entry and early replication for respiratory viruses), the spray may reduce viral attachment, entry or replication in the nose, thereby reducing the chance of infection or lowering viral loads.
• The reduction of local inflammation may make the environment less permissive for viral invasion or spread in the nasal passages.

Important Caveats and Limitations

While the findings are encouraging, several important warnings must be considered before broadly adopting azelastine for infection prophylaxis:

• The trial was single center, relatively small (450 participants), and the population was very homogeneous (average age ~33, 66% female, 93% white).
• It is a phase 2 trial, meaning that larger, multi site, diverse population studies are needed to confirm safety and efficacy in real-world settings.
• The use of azelastine does not replace vaccination, masking, ventilation, and other established public-health measures. Experts emphasise that vaccination remains the gold-standard for preventing severe COVID-19.
• Frequent dosing (three times daily, with increased dosing to five times daily after exposure or symptoms) may pose compliance challenges for many users.
• Side effects were mild but included bitter taste, nosebleeds, fatigue; although serious adverse events were rare and none were deemed related to the spray in this trial.
• Because the trial focused on healthy adults without chronic comorbidities, the efficacy in high-risk individuals (e.g., older adults, immunocompromised) is as yet unknown.

What Does This Mean for You?

For individuals considering incorporating azelastine nasal spray as an adjunct preventive measure, here are some practical considerations:

• Consult your healthcare provider before using a nasal spray off-label for infection prevention, especially if you have underlying nasal conditions, frequent nosebleeds, recent nasal surgery, are pregnant or breastfeeding. Some safety data in these groups is limited.
• Follow dosing instructions carefully: In the trial, participants used one puff in each nostril three times daily for 56 days, increasing to five times daily for three days after known exposure or symptoms.
• Use as one layer of protection: Continue to prioritise vaccination, mask usage in crowded indoor spaces, good ventilation, hand hygiene and staying home when sick. The nasal spray is not a substitute for these core interventions.
• Target periods of higher exposure risk: Some clinicians suggest that use may be particularly helpful during travel, crowded events, or in settings of elevated viral transmission at least until more large-scale evidence is available.
• Monitor for side-effects: While generally well-tolerated, users should be alert for nasal irritation, nosebleeds, bitter taste, dizziness, tiredness and discontinue use and consult a provider if problems arise.

Looking Ahead: What’s Next in Research

Researchers emphasise that the results are promising but preliminary. Larger, multi centre, randomized trials across diverse populations (including older adults, people with comorbidities, varied ethnicities) are needed to:

• Confirm the magnitude of risk reduction in everyday settings.
• Determine optimal dosing, duration, and cost-effectiveness of using azelastine prophylactically.
• Investigate whether it offers protection against other respiratory viruses beyond rhinovirus (e.g., influenza, RSV) and how it might complement vaccination and therapeutics.
• Explore long-term safety of frequent nasal use in broader populations.

If validated, using a readily available nasal spray for early prophylaxis could be a valuable addition to public-health strategies especially in high risk exposure settings or when new viral variants emerge.

The trial results for azelastine nasal spray offer an intriguing possibility: a cheap, easily accessible over-the-counter medication that may reduce the risk of both COVID-19 and common cold infections by a substantial margin (around 69 % and 71 %, respectively). However, the data are still early, and this approach should not replace established preventive measures like vaccination, masking and ventilation.

In short: promising but preliminary. For now, the best strategy remains a layered approach to respiratory infection prevention, and this nasal spray may become an additional tool in our toolbox pending further evidence.