The Scientific Pursuit of a Nasal Spray for COVID
For years, scientists have explored the potential of nasal sprays to combat respiratory viruses like SARS-CoV-2. The appeal lies in targeting the virus directly at its primary entry point: the nasal passages. This localized approach could, in theory, neutralize the virus before it spreads to the rest of the body. The goal is to either treat existing infections by reducing the viral load in the nose or prevent infections from taking hold altogether, a concept known as pre-exposure prophylaxis.
However, it is crucial to understand that the landscape of nasal sprays for COVID-19 is varied and complex. It includes repurposed over-the-counter medications, physical barriers, and novel intranasal vaccines. As of late 2025, no nasal spray has received FDA approval specifically as an antiviral treatment for COVID-19 in the United States, and claims of effectiveness for non-approved products are often met with regulatory warnings.
Promising Candidates in Clinical Trials
Several nasal spray products and technologies have shown promise in clinical studies, leading to cautious optimism among researchers. These candidates work through different mechanisms and are in various stages of development.
Azelastine: The Over-the-Counter Contender
Azelastine is a well-established antihistamine nasal spray sold under brand names such as Astepro and Astelin, commonly used to treat seasonal allergies. Early in the pandemic, laboratory studies suggested azelastine possessed antiviral properties against SARS-CoV-2, which prompted further investigation.
Most recently, a Phase 2 trial conducted in Germany and published in JAMA Internal Medicine in September 2025 provided encouraging results. The study found that regular application of azelastine nasal spray significantly reduced the incidence of PCR-confirmed SARS-CoV-2 infection in healthy adults compared to a placebo. The antihistamine appears to have an antiviral effect against a range of respiratory viruses, including the one that causes COVID. While these findings are promising and support further research, it is important to note that the FDA has not approved azelastine for the prevention or treatment of COVID-19, and experts emphasize that it should not replace vaccination.
Nitric Oxide Nasal Spray (NONS)
Nitric oxide is a naturally occurring molecule in the body with known antimicrobial properties. This led researchers to investigate nitric oxide nasal sprays (NONS), sold under brands like Enovid or VirX in countries where they have received authorization, such as Israel and Indonesia.
Small studies have suggested that NONS can reduce the viral load in patients with COVID-19 and potentially shorten the duration of contagiousness. The spray is thought to work by inhibiting viral replication in the nasal cavity. A large-scale Phase 3 prevention trial for NONS was ongoing as of late 2024. However, NONS is not FDA-approved for COVID-19 in the U.S..
Intranasal COVID-19 Vaccines
Distinct from antiviral medications, intranasal vaccines are designed to trigger a robust immune response specifically in the mucous membranes of the nose and respiratory tract. This targeted approach is intended to provide a better defense against infection at the portal of entry.
While several countries have authorized intranasal COVID vaccines, including China, India, and Russia, none are yet FDA-authorized in the U.S.. However, promising candidates are advancing through clinical trials in the United States, such as the vaccine developed by Washington University and licensed by Ocugen. This technology has the potential to provide broad immunity and better protection against future variants.
The Landscape of Other Nasal Spray Ingredients
In addition to azelastine and NONS, other nasal spray ingredients have been studied or marketed with claims of efficacy against respiratory viruses. These include:
- Iota-carrageenan: A polysaccharide derived from red algae, studied for its ability to form a barrier in the nasal passages. Some studies suggested it might reduce COVID-19 risk, but active research appears to have ceased as of late 2024.
- Xylitol: A sugar alcohol that, in some reports, is suggested to help reduce viral load and improve symptoms. Clinical trials are needed to confirm these anecdotal findings.
- Povidone iodine: An antiseptic used in some nasal rinses, which has shown some limited promise against COVID-19 in small studies.
- Steroid nasal sprays (e.g., Flonase): Primarily used for inflammation from conditions like allergies, some observational studies have explored their potential role in managing COVID-19 symptoms or reducing hospitalization risk, but research results have been mixed.
The FDA has issued warning letters to companies marketing products with iota-carrageenan, xylitol, or povidone iodine for COVID, as their claims were unverified and not supported by FDA authorization.
Comparison of Nasal Sprays for COVID
| Type | Active Ingredient | Primary Mechanism | FDA Status (for COVID in U.S.) | Evidence Status | Availability | Potential Use |
|---|---|---|---|---|---|---|
| Antihistamine | Azelastine | May have direct antiviral effect and reduce inflammation | Not FDA-approved | Promising Phase 2 data, warrants larger trials | Over-the-counter (for allergies) | Complementary prevention, not replacement for vaccine |
| Barrier | Nitric Oxide (NONS) | Forms a barrier, reduces viral load | Not FDA-approved | Ongoing Phase 3 trials | Available in certain countries only (e.g., Israel, Indonesia) | Potential preventative or early treatment |
| Barrier | Iota-carrageenan | Forms a barrier in nasal passages | Not FDA-approved | Limited studies, no active trials noted as of late 2024 | Varies by brand/country | Potentially preventative |
| Vaccine | Various | Induces mucosal immunity | None yet in U.S. | In clinical trials globally; some authorized abroad | Limited availability, if any, via clinical trials | Preventative immunity against infection |
The Importance of Rigorous Research
The promising findings for nasal spray candidates like azelastine and intranasal vaccines must be interpreted cautiously. Phase 2 trials, while encouraging, are designed to test safety and preliminary efficacy. Larger, multi-center Phase 3 trials are required to confirm reliable effectiveness across diverse populations. Regulatory bodies like the FDA play a critical role in scrutinizing this evidence to determine if a medication is safe and effective enough for widespread use.
Furthermore, the mechanism of action matters. While antihistamines and barrier sprays might offer some complementary protection, they should not be viewed as alternatives to proven measures like vaccination and masking. Vaccines are designed to prevent severe disease, hospitalization, and death, which is a different goal than simply reducing viral load in the nose.
Conclusion
The quest to find what is the antiviral nasal spray for COVID-19 continues, with significant progress made in recent years. The antihistamine azelastine has shown noteworthy potential for preventing infection in clinical trials, but further confirmation is needed before it could be considered a standard prophylactic measure. Meanwhile, intranasal vaccines are advancing through trials with the potential for targeted mucosal immunity, and other barrier sprays are still being explored.
For now, the most effective and reliable strategies for protecting against COVID-19 remain consistent: staying up-to-date with recommended vaccinations, practicing good hygiene, and considering other public health measures like masking when appropriate. Any decision to use a nasal spray off-label should be discussed with a healthcare professional, based on the latest evidence and your personal health situation.
Authoritative Link
To explore the specific results of the recent azelastine trial, readers can review the findings published in JAMA Internal Medicine: Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections: A Phase 2 Randomized Clinical Trial.
