New research suggests that eliminating the nasal virus that causes the symptoms may reduce allergic inflammation and open a new treatment avenue for the millions of people suffering from allergic rhinitis.
Study: Treatment of allergic rhinitis using ribavirin spray to eliminate commensal viruses in the nose. Image credit: Cinefootage Visuals / Shutterstock
In a recent study published in the journal Signal transduction and targeted therapyresearchers investigated how viruses present in the nasal cavity contribute to the development of allergic rhinitis (AR). In a small phase 2 trial, researchers found that removing commensal viruses from the nose with ribavirin nasal spray improved symptoms in mice, and that ribavirin spray improved symptoms in patients, suggesting a role for these viruses in AR development.
The virus, which normally resides in the nasal cavity without causing overt infection, activated innate immune sensors, leading to the accumulation of type I interferon (IFN)-associated neutrophils. These cells subsequently formed neutrophil extracellular traps (NETs) that appear to promote AR development.
AR is a common disease of the upper respiratory tract that causes frequent sneezing, nose rubbing, and itching. If left untreated, it can lead to nasal sinus obstruction in advanced cases. As a result, such a person may not sleep well and work less efficiently.
Scientists are therefore working to identify the biological pathways that drive AR progression and develop new strategies to target them and improve standard treatments. In particular, researchers are looking to investigate whether viruses that occupy the nasal passages contribute to the development of AR.
About research
In this study, researchers investigated the mechanism by which a virus that normally lives in the nose promotes AR development in mice. They then evaluated the safety and efficacy of ribavirin treatment in 43 AR patients (42 of whom were randomized) who were screened between April and May 2024.
The research team first developed a mouse model of AR. We then collected nasal lavage fluid (NLF) from these animals and identified viral populations within the nasal cavity. They administered intranasal ribavirin infusions daily for 7 days to reduce intranasal viral load and elucidate their role in the pathophysiology of AR. Next, they performed 16S ribosomal RNA amplicon sequencing on the collected NLF samples.
The researchers reintroduced NLF to control mice after ribavirin treatment and separately treated AR mice with favipiravir to test their results. Single-cell RNA sequencing (scRNA-seq) efforts have revealed the impact of viral commensals on nasal immune cell populations. The researchers also performed knockout experiments in which they deleted the innate sensor and transcription factor for IFN-related genes, followed by administering an IFN-α1b infusion.
The researchers then conducted the Ribavirin Spray Therapy for Allergic Rhinitis (R-STAR) study, a single-center, phase 2 randomized controlled trial (RCT). In this trial, participants received ribavirin or a placebo for four weeks. We then assessed AR symptoms using the Total Nasal Symptom Score (TNSS).
The research team also assessed secondary outcomes using Rhinitis Control Assessment Test (RCAT) scores and visual analogue scales (VAS). We also collected NLF from participants and tested them for cytokine levels, and tested serum-specific immunoglobulin E (IgE) levels to identify allergens. They further performed metatranscriptomic analysis to identify the most abundant viruses in AR patients.
result
In a mouse model, administration of ribavirin reduced the amount of commensal virus in the nose and improved AR symptoms such as sneezing and scratching. Nasal mucosal samples taken from these animals showed reduced numbers of eosinophils. These leukocytes often accumulate in allergic inflammation, and in such cases can contribute to chronic inflammatory responses and tissue damage. NLF also decreased the production of type I IFN and interleukin (IL) 4, 5, and 13, which attenuated mucosal pathology.
Among immune cells, neutrophils were most significantly decreased in the nasal mucosa of mice. Notably, neutrophil populations, which upregulate cluster of differentiation 14 (CD14) receptors and IFN-stimulated genes (ISGs) during inflammation, were reduced after ribavirin therapy.
Reintroducing NLF from controls restored post-ribavirin AR symptoms and type II cytokine production, whereas administration of favipiravir alone reduced AR symptoms and type II cytokine production, supporting this finding. Knockout of IFN-related genes and innate sensors also alleviated AR symptoms, but administration of IFN-α1b infusion worsened symptoms.
The R-STAR study provided initial clinical support for the findings. Ribavirin-treated patients showed significant reductions in nasal viral commensals and improved TNSS, RCAT, and VAS values after 4 weeks of treatment. Ribavirin therapy also significantly reduced IL-4, 5, 13, 17A cytokine levels and NET activity, and these cytokines were positively correlated with IFN-α and IFN-β in NLF samples.
This treatment also reduced viral sequences classified as Betaretrovirus genus and candidate Betaretrovirus species Environmental Animal Rhinous Tumor Virus 2 (ENTV-2) and Bovine Retrovirus CH15 (BoRV CH15) in the samples.
Treatment effects were more pronounced in participants with severe symptoms and high nasal commensal viral loads, and some effects persisted at 1-year follow-up after a 4-week treatment course.
The research team identified dust mites and sensitization to dust mites as the most common allergens. Half of the participants tested positive. Three participants required rescue medications such as cetirizine or emedastine to manage AR symptoms. There were no grade 3 or higher adverse events, serious adverse events, or side effects.
conclusion
This discovery reveals a new mechanism driving AR development and an innovative approach to treating affected individuals.
These results suggest that virus present in the nasal cavity may worsen AR symptoms and that ribavirin may be a promising investigational treatment strategy with long-term efficacy.
If validated in further studies, ribavirin could provide an alternative treatment to existing treatments such as glucocorticoid nasal sprays, antihistamines, and allergen immunotherapy by addressing limitations associated with treatment-associated side effects and variable long-term efficacy. However, larger multicenter phase 3 trials are needed, nasal viruses can recur after treatment discontinuation, and candidate viruses associated with human AR require further causal testing.
The authors also note that ribavirin may affect bacteriophages and the nasal bacterial ecosystem.
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Reference magazines:
- Zhou, Y., Wang, T., Fan, Y., et al. (2026). Treatment of allergic rhinitis with ribavirin spray, which removes commensal viruses in the nose. Signal Transduction and Targeted Therapy, 11, 249. Doi: 10.1038/s41392-026-02744-y. https://www.nature.com/articles/s41392-026-02744-y
