Therapy of allergic rhinitis using ribavirin spray to clear nasal commensal viruses

Much attention has focused on commensal bacteria in health and disease, but the role of commensal viruses is largely unexplored. Although commensal viruses are suggested in some organs such as intestine to maintain tissue homeostasis, it is unknown whether they participate in the physiology or pathology of nose, which directly contacts outer environment. Here, we focused on nasal commensal viruses in the development of allergic rhinitis (AR), a global health problem affecting 20% to 30% of the population, and found that clearance of nasal commensal viruses using ribavirin alleviated AR symptoms, suggesting that these viruses contribute to AR pathogenesis. Mechanistically, nasal commensal viruses, recognized by innate sensors, initiated the production of type I interferon, recruiting and generating a population of interferon-induced neutrophils in the nasal cavity, which released neutrophil extracellular traps (NETs) to promote AR. Most importantly, to verify whether clearing nasal commensal viruses could treat AR patients clinically, we performed a randomized, double-blind, placebo-controlled, phase 2 clinical trial (Chinese Clinical Trial Registry identifier: www.chictr.org.cn ChiCTR2400082642) to explore the efficacy and safety of ribavirin spray in treating AR patients, and found that the patients of ribavirin group experienced significantly reduced nasal commensal viruses and alleviated symptoms as compared to the placebo group, determining the therapeutic efficacy of ribavirin spray. Thus, we suggest a new mechanism for AR and a new approach for treating AR patients.