The COVID-19 pandemic prompted extensive research into interventions beyond traditional vaccines and oral medications. Nasal sprays emerged as a potential tool to combat the SARS-CoV-2 virus. These sprays act directly at the primary site of infection—the nose and upper respiratory tract—where the virus first enters and replicates. This localized approach aims to prevent infection or reduce disease severity by targeting the virus before it spreads.
How Nasal Sprays Combat COVID-19
Nasal sprays combat COVID-19 through several mechanisms within the nasal passages.
Some sprays create a physical barrier, such as a gel or film, on the nasal lining. This barrier traps inhaled viral particles, preventing them from attaching to host cells. For example, bentonite-containing sprays form a durable, protective gel that blocks viruses.
Other sprays contain active ingredients that neutralize the virus. These agents bind to SARS-CoV-2, disrupting its structure or blocking its interaction with human cell receptors like ACE2, which the virus uses for entry. Some compounds, for instance, can reduce viral RNA generation in early replication.
Some formulations boost the local immune response within the nasal cavity. By stimulating antibody production, particularly immunoglobulin A (IgA) in the nasal mucosa, these sprays enhance the body’s natural defenses at the virus’s entry point. This localized response can prevent viral spread and limit transmission.
Nasal sprays reduce viral replication, lowering the viral load in the nasal passages. A decreased viral load makes an infected individual less infectious to others, acting as source control. For healthy individuals, inactivating the virus in the nose can help prevent infection.
Current Landscape of COVID-19 Nasal Sprays
COVID-19 nasal sprays are broadly categorized by their intended purpose.
Preventative sprays reduce infection risk, often used before or after potential exposure. Therapeutic sprays treat existing infections, reducing viral load or mitigating symptoms.
These sprays utilize various agents. Some formulations contain antivirals that target viral replication or attachment. For example, the antiviral molecule N-0385 has shown promise in mice, protecting against infection and treating the virus. Others incorporate antibodies or compounds that block viral attachment to host cells, interfering with the interaction between the viral spike protein and the ACE2 receptor.
Natural substances like carrageenan, derived from red seaweed, can inhibit SARS-CoV-2 infection in cell models. Nitric oxide nasal sprays have also been developed and found to reduce viral loads. The development status of these sprays varies; some have received emergency use authorization in regions like India and China, while others remain in various phases of clinical trials globally. In the United States, no nasal sprays are currently authorized by the FDA to fight COVID-19.
Efficacy and Safety of Nasal Sprays
Clinical trials have provided insights into the effectiveness and safety of COVID-19 nasal sprays.
Some studies have indicated that certain nasal sprays can significantly reduce SARS-CoV-2 viral load, even in patients with high viral concentrations. For instance, a nitric oxide nasal spray demonstrated a reduction in viral load and was effective against the UK variant of the virus. In one randomized, double-blind, placebo-controlled phase 2 trial involving 79 patients, the spray significantly decreased SARS-CoV-2 levels when administered early after diagnosis.
Further research into prophylactic nasal sprays has shown promising results in preventing infection. A multi-center, double-blind, placebo-controlled, randomized trial found that a novel prophylactic nasal spray significantly reduced the infection rate from 34.5% in the placebo group to 13.1% in the treated group among high-risk healthcare workers. This study also reported fewer symptomatic cases in the group using the test agent, with 17.6% experiencing symptoms compared to 34.6% in the placebo group.
Regarding safety, clinical trials generally report that nasal sprays are well-tolerated, with a benign safety profile. Common side effects, when reported, are typically mild and localized to the application site, such as a temporary tingling or stinging sensation. For example, the SA58 Nasal Spray reported an adverse event incidence of 28.6%, with the majority being mild and from the administrative site. However, some sprays, particularly those containing povidone-iodine, may have contraindications for individuals with thyroid disease, pregnant individuals, or those with allergies to iodine-containing products.
While nasal sprays offer a convenient and needle-free delivery method, their role compared to established interventions like vaccines and oral antivirals is still being defined. Vaccines induce systemic immunity, providing broad protection, whereas nasal sprays primarily focus on mucosal immunity at the initial site of infection. The ongoing research aims to understand how these localized treatments can complement existing strategies in preventing and treating COVID-19.