Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial

Silveira, Marcelo Augusto Duarte; Jong, David De; Berretta, Andresa Aparecida; Galvão, Erica Batista dos Santos; Caldas, Juliana; Cerqueira‐Silva, Thiago; Amorim, Thais Chaves; Conceição, Luis Filipe Miranda Rebelo da; Gomes, Marcel Miranda Dantas; Teixeira, Maurício Brito; Souza, Samilly Evangelista; Santos, Marcele Helena Celestino Alves Dos; Martin, Raíssa Lanna Araújo San; Silva, Márcio de Oliveira; Lirio, M. Isabel Vargas; Moreno, Lis; Sampaio, Julio Cezar Miranda; Mendonça, Renata Navis de Avila; Ultchak, Silviana Salles; Amorim, Fabio Santos; Ramos, João Gabriel Rosa; Batista, Paulo Benígno Pena; Guarda, Suzete Nascimento Farias da; Mendes, Ana Verena Almeida; Passos, Rogério da Hora

doi:10.1016/j.biopha.2021.111526

Cited by 98 publications

(111 citation statements)

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“…Standardized Brazilian green propolis extract (EPP-AF) was used at two different doses (low and high doses). This study included 124 patients who were divided into three groups: the control group (n = 42), the EPP-AF group receiving 400 mg/day (n = 40), and the EPP-AF group receiving 800 mg/day (n = 42) [2].…”

Section: Propolis: Experimental Evidence Against Viral Targetsmentioning

confidence: 99%

“…The length of hospital stay postintervention was shorter in both propolis groups than in the control group: in the low dose group, the median stay was 7 days versus 12 days (95% con dence interval [CI] − 6.23 to − 0.07; p = 0.049); and in the high dose group, the median stay was 6 days versus 12 days (95% CI − 7.00 to − 1.09; p = 0.009) [two]. The patients who received EPP-AF at the highest dose had a signi cantly lower rate of acute kidney injury than those in the control group (23.8% vs. 4.8%, p = 0.048) [2]. The study had limitations: it was an open, single-center study and did not include a placebo group.…”

Section: Propolis: Experimental Evidence Against Viral Targetsmentioning

confidence: 99%

“…The dose of standardized Brazilian green propolis extract was chosen based on studies that used similar doses without observing adverse effects [2,5,13]. The propolis extract being used in this study was prepared from a single batch to ensure for uniformity.…”

Section: Treatment Groups and Justi Cation Of Dose Usedmentioning

confidence: 99%

“…The COVID-19 pandemic is of great concern because of its unprecedented impact on human health [1]. The disease, after the replication phase, promotes in ammatory and immunological events, and even with advances in knowledge of its pathophysiology, we still do not have a speci c treatment [2].…”

Section: Introductionmentioning

confidence: 99%

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The Use of Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2): A Structured Summary of a Study Protocol for a Randomized Controlled Trial

Silveira

Souza

Galvão

et al. 2021

Preprint

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Background The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. To date, there is no consensus on a specific treatment. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study is once again assessing EPP-AF in hospitalized patients with coronavirus infection. Methods BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days who are not on invasive oxygen therapy are eligible. Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the length of hospital stay. Secondary outcomes include the need for mechanical ventilation, the rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). Discussion This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. Trial registration: ClinicalTrials.gov NCT04800224. Registered on March 16, 2021.

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Section: Propolis: Experimental Evidence Against Viral Targetsmentioning

confidence: 99%

Section: Propolis: Experimental Evidence Against Viral Targetsmentioning

confidence: 99%

Section: Treatment Groups and Justi Cation Of Dose Usedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Use of Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2): A Structured Summary of a Study Protocol for a Randomized Controlled Trial

Silveira

Souza

Galvão

et al. 2021

Preprint

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“…Moreover, the impact generated by the pandemic COVID-19 has motivated the studies of propolis in action against infection by SARS-CoV-2 ( Berretta et al, 2020 ; Refaat et al, 2021 ), whereas this natural product has anti-inflammatory properties ( Lima et al, 2014 ; Washio et al, 2015 ; Kitamura et al, 2018 ) and action against some virus species ( Hazem et al, 2017 ; Kwon et al, 2020 ). Recently, a clinical trial conducted in Brazil (National Clinical Trial Number: NCT04480593) has shown the efficacy of green propolis in supporting treatment in patients hospitalized with COVID-19 ( Silveira et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Red Propolis as a Source of Antimicrobial Phytochemicals: Extraction Using High-Performance Alternative Solvents

et al. 2021

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Propolis is a resinous material rich in flavonoids and involved in several biological activities such as antimicrobial, fungicide, and antiparasitic functions. Conventionally, ethanolic solutions are used to obtain propolis phytochemicals, which restrict their use in some cultures. Given this, we developed an alcohol-free high-performance extractive approach to recover antibacterial and antioxidants phytochemicals from red propolis. Thus, aqueous-solutions of ionic liquids (IL) and eutectic solvents were used and then tested for their total flavonoids, antioxidant, and antimicrobial activities. The surface-responsive technique was applied regarding some variables, namely, the time of extraction, the number of extractions, and cavitation power (W), to optimize the process (in terms of higher yields of flavonoids and better antioxidant activity). After that, four extractions with the same biomass (repetitions) using 1-hexyl-3-methylimidazolium chloride [C6mim]Cl, under the operational conditions fixed at 3.3 min and 300 W, were able to recover 394.39 ± 36.30 mg RuE. g−1 of total flavonoids, with total antioxidant capacity evaluated up to 7595.77 ± 5.48 μmol TE. g−1dried biomass, besides inhibiting the growth of Staphylococcus aureus and Salmonella enteritidis bacteria (inhibition halo of 23.0 ± 1.0 and 15.7 ± 2.1, respectively). Aiming at the development of new technologies, the antimicrobial effect also presented by [C6mim]Cl may be appealing, and future studies are required to understand possible synergistic actions with propolis phytochemicals. Thereby, we successfully applied a completely alcohol-free method to obtain antimicrobials phytochemicals and highly antioxidants from red propolis, representing an optimized process to replace the conventional extracts produced until now.

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Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

et al. 2023

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ImportanceRandomized clinical trials (RCTs) on COVID-19 are increasingly being posted as preprints before publication in a scientific, peer-reviewed journal.ObjectiveTo assess time to journal publication for COVID-19 RCT preprints and to compare differences between pairs of preprints and corresponding journal articles.Evidence ReviewThis systematic review used a meta-epidemiologic approach to conduct a literature search using the World Health Organization COVID-19 database and Embase to identify preprints published between January 1 and December 31, 2021. This review included RCTs with human participants and research questions regarding the treatment or prevention of COVID-19. For each preprint, a literature search was done to locate the corresponding journal article. Two independent reviewers read the full text, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Time to publication was analyzed using a Cox proportional hazards regression model. Differences between preprint and journal article pairs in terms of outcomes, analyses, results, or conclusions were described. Statistical analysis was performed on October 17, 2022.FindingsThis study included 152 preprints. As of October 1, 2022, 119 of 152 preprints (78.3%) had been published in journals. The median time to publication was 186 days (range, 17-407 days). In a multivariable model, larger sample size and low risk of bias were associated with journal publication. With a sample size of less than 200 as the reference, sample sizes of 201 to 1000 and greater than 1000 had hazard ratios (HRs) of 1.23 (95% CI, 0.80-1.91) and 2.19 (95% CI, 1.36-3.53) for publication, respectively. With high risk of bias as the reference, medium-risk articles with some concerns for bias had an HR of 1.77 (95% CI, 1.02-3.09); those with a low risk of bias had an HR of 3.01 (95% CI, 1.71-5.30). Of the 119 published preprints, there were differences in terms of outcomes, analyses, results, or conclusions in 65 studies (54.6%). The main conclusion in the preprint contradicted the conclusion in the journal article for 2 studies (1.7%).Conclusions and RelevanceThese findings suggest that there is a substantial time lag from preprint posting to journal publication. Preprints with smaller sample sizes and high risk of bias were less likely to be published. Finally, although differences in terms of outcomes, analyses, results, or conclusions were observed for preprint and journal article pairs in most studies, the main conclusion remained consistent for the majority of studies.

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Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial

Cited by 98 publications

References 56 publications

The Use of Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2): A Structured Summary of a Study Protocol for a Randomized Controlled Trial

The Use of Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2): A Structured Summary of a Study Protocol for a Randomized Controlled Trial

Red Propolis as a Source of Antimicrobial Phytochemicals: Extraction Using High-Performance Alternative Solvents

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles

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