Abstract
<title>Abstract</title> <p> <bold>Background</bold> To evaluate the efficacy of a slow-release mucoadhesive paste containing 3% Carvacrol (Mucodentol) applied to the oral vestibule in preventing the onset and severity of COVID-19 symptoms among high-risk healthcare personnel. <bold>Methods</bold> A triple-blind, randomized, placebo-controlled field trial was conducted on 1,624 asymptomatic healthcare workers in COVID-19 center hospitals. Participants were randomly assigned to use either Mucodentol or an identical placebo paste three times daily for four weeks. The primary outcome was the total symptom severity score, assessed weekly via telephone interviews. Data were analyzed using an intention-to-treat approach with Generalized Estimating Equations (GEE) to model the effect of the intervention over time, adjusting for key confounding variables. <bold>Results</bold> Analysis with the GEE model, after adjusting for covariates, revealed a statistically significant group-by-time interaction for the total symptom severity score (p < 0.001), indicating a time-dependent treatment effect. Mucodentol demonstrated significant benefits for a range of specific symptoms, including dry cough, shortness of breath, fatigue, myalgia, and ageusia (loss of taste). The intervention's effect on individual symptoms varied dynamically over the study period, with some showing increasing benefits over time. <bold>Conclusions</bold> The analysis revealed that Mucodentol provided a significant and progressively evolving benefit in reducing overall symptom severity over the course of the study (p < 0.001), after adjusting for key confounding variables. <bold>Trial registration</bold> IRCT20130428013151N2 '( 20200506), https//en.irct.ir/trial/49356. </p>