Preventing SARS-CoV-2 Infection with an Allergy Nasal Spray
October 15, 2025
By Stan Deresinski, MD, FIDSA
Synopsis: Use of the antihistamine azelastine nasal spray was effective in preventing SARS-CoV-2 infection in young, healthy, vaccinated outpatients.
Source: Lehr T, Mesier P, Selzer D, et al; CONTAIN Study Group. Azelastine nasal spray for prevention of SARS-CoV-2 infections: A phase 2 randomized clinical trial. JAMA Intern Med. 2025;Sep 2:e254283. doi:10.1001/jamainternmed.2025.428. [Online ahead of print].
Lehr and colleagues performed a randomized placebo-controlled trial examining the ability of azelastine, an over-the-counter antihistamine nasal spray, to prevent infection with SARS-CoV-2. The study was performed during March 2023 to July 2024. They enrolled 450 healthy volunteers (223 randomized to placebo and 227 to azelastine 0.1% nasal spray) with a mean age of 33.5 years; 66.4% were female. A single puff (0.14 mL) of the assigned spray was applied in each nostril three times a day for a mean of 56 days. The placebo contained all the excipient components of the active drug.
In addition to being young and healthy, 99.1% had received at least one vaccine dose, with a median number of doses of three having been received. The median interval since the last vaccine dose was 672 days. Among those tested at baseline, serum antibody directed at nucleocapsid and spike antigens was detected in 65.2% and 71.3% of azelastine and placebo recipients, respectively.
The primary study endpoint, the occurrence of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection in the intention-to-treat (ITT) population, was significantly lower in the azelastine group (5/227; 2.2%) than the placebo group (15/223; 6.7%). This resulted in a risk difference (RD) of -4.5 (95% confidence interval [CI], -8.3 to -0.7 percentage points; P = 0.02). The results were similar in a per-protocol analysis as well as an analysis limited to symptomatic infections. Azelastine administration also was associated with a longer interval to onset of SARS-CoV-2 infection and a shorter duration of reported antigen test positivity.
Azelastine was associated with a bitter taste in the mouth in 9.3% vs. 1.3% in placebo recipients but otherwise was well tolerated. In addition to preventing SARS-CoV-2 infection, azelastine use was associated with a lower incidence of rhinovirus infection — 1.8% vs. 6.3%. There was no apparent difference in occurrence of other respiratory infections, but the numbers of each were quite low. However, including all PCR-confirmed respiratory viral infections, the incidence was 9.3% in azelastine recipients and 22.0% in those assigned to receive placebo.
Commentary
Azelastine is a second-generation antagonist of the H1 receptor that is available without prescription. Previous work had demonstrated its activity against all tested strains of SARS-CoV-2, as well as against respiratory syncytial virus and influenza A (H1N1) virus. Prior work found evidence of reduction in SARS-CoV-2 viral load in infected patients.1,2 The mechanism of antiviral activity against SARS-CoV-2 is unproven but has been suggested to be related to host cell receptors such as angiotensin-converting enzyme (ACE)-2 and, possibly, viral protease. Similarly, activity against rhinovirus may be related to inhibition of a key host cell receptor for this virus, ICAM-1.
Monoclonal antibodies, such as sotrovimab, effectively prevented SARS-CoV-2 infection — until the virus evolved resistance to it. A recent placebo-controlled randomized trial in cancer patients found a 40% reduction in risk of infection with prophylactic use of nasal interferon-α, although there was no apparent benefit in prevention of other respiratory virus infections.3 Although not strictly speaking a prophylactic trial of the same sort, nirmeltravir-ritonavir was found to be ineffective in preventing COVID-19 after exposure.4 The study by Lehr et al demonstrated prophylactic efficacy of azelastine, but in a young, healthy population. In contrast, pemivibart, a neutralizing monoclonal antibody, has been shown to prevent COVID-19 in individuals with moderate to severe immunocompromise and is now recommended in the Infectious Diseases Society of America (IDSA) guideline.5,6
Nasal application of azelastine appears to be effective in the prophylaxis of SARS-CoV-2 infection, at least in young, healthy, vaccinated individuals. One could consider its use in that group, but whether it is effective in a wider group of less healthy individuals with moderate to severe immunocompromise remains to be seen.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
References
- Klussmann JP, Grosheva M, Meiser P, et al. Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients. Sci Rep. 2023;13(1):6839.
- Meiser P, Flegel M, Holzer F, et al; Carvin-Ii Study Group. Azelastine nasal spray in non-hospitalized subjects with mild COVID-19 infection: A randomized placebo-controlled, parallel-group, multicentric, phase II clinical trial. Viruses. 2024;16 (12):1914.
- Yong MK, Thursky K, Crane M, et al. Interferon-α nasal spray prophylaxis reduces COVID-19 in cancer patients: A randomized, double-blinded, placebo-controlled trial. Clin Infect Dis. 2025; Aug 28:ciaf409. doi: 10.1093/cid/ciaf409. [Online ahead of print].
- Hammond J, Yunis C, Fountaine RJ, et al. Oral nirmatrelvir-ritonavir as postexposure prophylaxis for Covid-19. N Engl J Med. 2024;391(3):224-234.
- Wolfe CR, Cohen J, Mahoney K, et al. Safety and efficacy of pemivibart, a long-acting monoclonal antibody, for prevention of symptomatic COVID-19: Interim results from a Phase 3 randomized clinical trial (CANOPY). Clin Infect Dis. 2025;May 24:ciaf265. doi: 10.1093/cid/ciaf265. [Online ahead of print].
- Bhimraj A, Falck-Ytter Y, Kim AY, et al. 2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on the Management of COVID-19: Anti-SARS-CoV-2 Neutralizing Antibody Pemivibart for Pre-exposure Prophylaxis. Clin Infect Dis. 2024; Oct 29:ciae435. [Online ahead of print].
Use of the antihistamine azelastine nasal spray was effective in preventing SARS-CoV-2 infection in young, healthy, vaccinated outpatients.
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