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REVIEW ARTICLE

Greek poplar-type propolis as an adjunct therapy in hospitalized COVID-19 adults: A randomized controlled trial protocol

Giorgos Tzigkounakis1* ,  Jonathan Brown2
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1 Department of Research, Health and Resilience Institute, Athens, Greece
2 Department of Nutrition, Food and Exercise Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom
JCTR, 00073 https://doi.org/10.36922/jctr.24.00073
Received: 30 October 2024 | Revised: 11 March 2025 | Accepted: 26 March 2025 | Published online: 16 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: Despite the rapid development and distribution of COVID-19 vaccines, the pandemic continues to challenge global health systems. With vaccine inequity and hesitancy, especially in low-income populations and specific demographic cohorts, alternative therapeutic strategies to mitigate COVID-19 symptoms and reduce viral clearance time remain vital. Propolis, a natural bee product with immunomodulatory and antiviral properties, has demonstrated efficacy against other viral pathogens, suggesting potential as an adjunctive therapy for COVID-19. Objectives: This study protocol outlines a randomized, triple-blind, placebo-controlled clinical trial to assess the efficacy of a Greek propolis hydroalcoholic extract as an adjunct to standard care in hospitalized COVID-19 patients. The primary objectives are to evaluate the extract’s impact on viral clearance time and hospitalization duration, with secondary objectives examining body temperature, cough severity, quality of life, and safety. Methods: A total of 441 severe acute respiratory syndrome coronavirus 2-positive adult patients will be enrolled and stratified by age and vaccination status. Participants will be randomly assigned to one of three arms: (i) propolis extract, (ii) placebo, or (iii) control (standard care only). Primary outcomes include time to negative reverse transcription polymerase chain reaction tests and hospital discharge. Secondary measures involve cough severity and quality-of-life assessments through Visual Analog Scale and Leicester Cough Questionnaire scores, fever duration and resolution patterns, and safety through adverse events and mortality tracking. Statistical analysis will include Kaplan–Meier survival curves, Cox regression for confounders, and analysis of variance for quality-of-life scores. Conclusion: This study aims to validate the therapeutic potential of propolis as a natural, accessible adjunctive treatment for COVID-19. Findings may provide critical evidence supporting propolis in symptom relief, viral clearance, and healthcare burden reduction in resource-limited settings. Relevance for patients: Participants in the intervention arm may experience improved clinical outcomes, such as faster recovery and symptom alleviation, while all patients will continue to receive standard care in alignment with current clinical protocols.

Keywords
SARS-CoV-2
COVID-19
Propolis
Adjunct therapy
Nutraceuticals
Randomized controlled trial
Immune modulation
Funding
None.
Conflict of interest
The authors declare no conflict of interest.
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