Efficacy of Nasal Spray, Mouth Spray, and Mouthwash Containing Limonene, Cetylpyridinium Chloride, and Monolaurin in COVID-19 Management: A Double-Blind, Randomized, Placebo-Controlled Trial

Introduction: COVID-19 predominantly affects the respiratory tract, leading to symptoms such as fever, sore throat, cough, and nasal congestion. This study aimed to evaluate the efficacy and safety of nasal spray, mouth spray, and mouthwash containing limonene, cetylpyridinium chloride (CPC), and monolaurin in alleviating symptoms among patients with mild-to-moderate COVID-19. Methods: A double-blind, randomized, placebo-controlled trial was conducted at Dontum Hospital, Thailand, from May to November 2022. A total of 120 RT-PCR–confirmed COVID-19 patients were randomly assigned to receive either the active antiviral formulations or placebo products. Symptom severity was assessed on Days 1, 3, and 7 using a 7-point Likert scale. Patient satisfaction regarding symptom relief and product attributes (color, smell, taste) was evaluated on Day 7 using a 5-point Likert scale. The study was approved by the Ethics Committee of Silpakorn University (COE 65.0517-081) and registered with the Thai Clinical Trials Registry (TCTR20240803002). Results: Compared to the placebo group, the experimental group exhibited significantly faster symptom resolution, particularly for sore throat, cough with mucus, and nasal congestion, with notable improvements observed as early as Day 3 (p < 0.05). By Day 7, a higher proportion of patients in the experimental group reported complete recovery (p < 0.05). Additionally, patient satisfaction scores for symptom relief and product characteristics were significantly higher in the experimental group (p < 0.001). No adverse events were reported in either group. Conclusion: The nasal spray, mouth spray, and mouthwash formulations containing limonene, CPC, and monolaurin were effective and well-tolerated in managing mild-to-moderate COVID-19 symptoms. These findings suggest their potential as adjunctive therapies in outpatient settings. Further large-scale, multicenter studies are warranted to confirm these results and assess long-term clinical benefits. Trial Registration: Thai Clinical Trials Registry (TCTR20240803002).