Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial
Marcelo Augusto Duarte Silveira, David De Jong, Andresa Aparecida Berretta, Erica Batista Dos Santos Galvão, Juliana Caldas Ribeiro, Thiago Cerqueira-Silva, Thais Chaves Amorim, Luis Filipe Miranda Rebelo Da Conceição, Marcel Miranda Dantas Gomes, Maurício Brito Teixeira, Sergio Pinto De Souza, Marcele Helena Celestino Alves Dos Santos, Raissa Lanna Araújo San Martin, Márcio De Oliveira Silva, Monique Lírio, Lis Moreno, Julio Cezar Miranda Sampaio, Renata Mendonça, Silviana Salles Ultchak, Fabio Santos Amorim, João Gabriel Rosa Ramos, Paulo Benigno Pena Batista, Suzete Nascimento Farias Da Guarda, Ana Verena Almeida Mendes, Rogerio Da Hora Passos
Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2021.111526
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. Methods: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF® ) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. Results: We enrolled 124 patients; 40 were assigned to EPP-AF® 400 mg/day, 42 to EPP-AF® 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate
Author Contributions MADS designed the trial and was the principal investigator, with overall responsibility for conducting the trial and for medical oversight of trial implementation and wrote the final report. RHP, SNFG, AVAM, JGR, and PBPB were responsible for the study design with the principal investigator. DDJ, AAB and RHP wrote the final report. JCR and TCS were responsible for analyzing the data. EBSG, RLASM, and TCA were responsible for coordinating and organizing the participants' data. SPS, LFMRC, MMDG, MBT, MHCAS, MOS, ML, SSU, and FSA contributed to the clinical and operational implementation of the trial. All authors contributed to trial design and interpretation of data and reviewed the final report.
Conflict of interest statement Dr. Berretta is an employee of Apis Flora. Dr. Silveira and all the other authors, except for Dr. Berretta and Dr. De Jong, are employed by the São Rafael hospital, which is part of the D'Or Institute for Research and Education.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at doi:10.1016/j.biopha.2021.111526.
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