Efficacy and Advantages of Nasopharyngeal and Oropharyngeal Treatments for Early Intervention and Prophylaxis in Respiratory Viral Infections: A Systematic Review and Meta-Analysis (2025)
Abstract:
Nasopharyngeal and oropharyngeal (NP/OP) treatments targeting the upper respiratory tract demonstrate significant efficacy in reducing the risk of progression and transmission of respiratory viral infections, including SARS-CoV-2. This systematic review synthesizes data from 66 clinical studies and multiple meta-analyses, evaluating compounds such as povidone-iodine, iota-carrageenan, nitric oxide, and others with established safety profiles. Early treatment or prophylaxis yields a lower risk profile, with efficacy rates of 38% [25-49%] for oral application, 56% [48-63%] for nasal application, and 91% [74-97%] for combined nasal and oral administration. Targeted delivery to the primary site of infection offers direct action, rapid onset, higher local drug concentrations, and reduced systemic side effects. Despite regulatory challenges, evidence supports the potential of NP/OP treatments as safe, cost-effective interventions, with polytherapy enhancing efficacy (68% [57-77%] risk reduction) compared to monotherapy (33% [30-36%]). Further research is warranted to optimize administration and address variant-specific efficacy.
Introduction:
The upper respiratory tract serves as the primary entry point for many viral pathogens, including SARS-CoV-2. Early intervention or prophylaxis targeting this region with nasopharyngeal/oropharyngeal (NP/OP) treatments has emerged as a promising strategy to mitigate infection progression and transmission. This review evaluates the efficacy, administration methods, and advantages of NP/OP treatments, drawing on 66 clinical studies and supporting meta-analyses. Compounds with established safety profiles, such as povidone-iodine, iota-carrageenan, and nitric oxide, are assessed alongside emerging treatments, with a focus on their potential to address respiratory pathogens efficiently.Methods:
Data were compiled from 66 clinical studies (references 11-83) and corroborated by meta-analyses (references 84-86), sourced from c19early.org. Studies employed various administration methods, including nasal sprays, oral rinses, nasal irrigation, and inhalation. Efficacy was quantified as risk reduction percentages with 95% confidence intervals for oral (38% [25-49%]), nasal (56% [48-63%]), and combined nasal/oral (91% [74-97%]) applications. Additional analyses compared monotherapy (33% [30-36%]) and polytherapy (68% [57-77%]) outcomes. Web-based searches and X posts were utilized where applicable to contextualize regulatory challenges and treatment availability as of April 06, 2025.Results:
NP/OP treatments demonstrate efficacy in reducing viral progression and transmission, even with delayed administration. Combined nasal and oral application achieves the highest efficacy (91% [74-97%]), surpassing nasal (56% [48-63%]) and oral (38% [25-49%]) methods alone. Advantages include direct targeting of the initial infection site, rapid onset, elevated local drug concentrations, and minimal systemic side effects. Administration parameters (e.g., viscosity, mucoadhesion, spray angle) influence outcomes, with optimal nasal spray angles potentially increasing drug delivery 100-fold (Figure 4, adapted from Akash et al.). Polytherapy significantly enhances efficacy (68% [57-77%]) compared to monotherapy (33% [30-36%]), supported by synergistic effects observed in trials combining treatments like ivermectin with niclosamide or nigella sativa with vitamin D. However, only 4% of studies directly targeted the upper respiratory tract, highlighting a research gap. A 621-patient randomized controlled trial (RCT) reported 92% lower transmission with NP/OP sprays, corroborated by a 200-patient RCT with 421 close contacts.Discussion:
NP/OP treatments offer a compelling approach to managing respiratory viral infections due to their targeted delivery and favorable safety profiles. Compounds such as povidone-iodine, chlorhexidine, and iota-carrageenan are widely available, yet regulatory barriers—e.g., U.S. FDA actions against povidone-iodine and SaNOtize—limit their adoption for COVID-19 indications, despite evidence from seven RCTs and international availability (e.g., SaNOtize in Israel, NoriZite in the UK). Emerging treatments like cetylpyridinium chloride and hypochlorous acid show promise in reducing viral load, though controlled clinical outcome data are lacking. Efficacy varies across SARS-CoV-2 variants, cell types, and genetic profiles, underscoring the value of polytherapy to address viral evolution and escape mutants. Potential disruptions to beneficial microbial populations necessitate selective treatment design for prolonged use.Conclusion:
NP/OP treatments provide a safe, inexpensive, and effective means of reducing respiratory viral progression and transmission, with combined nasal/oral administration and polytherapy yielding superior outcomes. Despite regulatory hurdles, their advantages warrant accelerated research to optimize delivery and identify novel applications following the emergence of new pathogens. Evidence-based protocols integrating multiple treatments offer the most robust defense against variant-specific challenges.References:
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