Codivir suppresses SARS-Cov-2 viral replication and stabilizes clinical outcome: In vitro and Phase I clinical trial results.

BACKGROUND: Treatment of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) remains a significant challenge in the face of increased worldwide morbidity and mortality. The acute illness caused by SARS-CoV-2 is initiated by a viral phase, followed by an inflammatory phase. Numerous anti-inflammatory and anti-viral therapies, with a relatively minor clinical effect, have been applied. Developing a safe and efficient direct anti-viral treatment is essential as it can block disease progression before significant complications ensue and potentially prevent transmission. AIM: The present phase 1 study aimed to determine the safety of Codivir, a newly developed anti-viral agent, and to preliminarily assess its anti-viral activity in patients infected by COVID-19. METHODS: In vitro studies were conducted to determine the direct anti-viral effect of Codivir using an immunofluorescence-based assay and to assess its cytotoxic effect by tetrazolium assay (MTT). In a phase I clinical trial, Codivir was administered for ten days in 12 patients who were followed for its safety. Patients were followed for clinical manifestations during administration. Sequential nasal viral PCR titers (Cycle Threshold, CT) were determined preceding and during treatment. RESULTS: In vitro, Codivir showed activity against SARS-CoV-2 with 90% viral replication suppression and minimal cytotoxicity. The anti-viral activity was demonstrated at the early stages of infection, post-entry of the virus in the cell. Codivir was safe in all 12 patients in phase I clinical trial and significantly suppressed viral replication in 5/7 fully assessed patients, with an anti-viral effect noted as early as three days. SUMMARY: The present study's data support the safety of Codivir administration in humans and suggest its significant anti-COVID-19 effect. These results support the testing of the drug in more extensive controlled trials in patients with SARS-CoV-2.

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial.

BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

Corrigendum to "Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial." [EClinicalMedicine 37 (2021) 100981].

[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].

Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis.

INTRODUCTION: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. OBJECTIVE: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. METHOD: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. RESULTS: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). CONCLUSION: The EN2 test showed high specificity (89%) and low sensitivity (66%).

Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis / Proteína EN2 urinária no diagnóstico do câncer de próstata: revisão sistemática e metanálise

Summary Introduction: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. Objective: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. Method: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. Results: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). Conclusion: The EN2 test showed high specificity (89%) and low sensitivity (66%).

Resumo Introdução: O câncer de próstata é o segundo tipo de câncer diagnosticado e a quinta causa de morte em homens em todo o mundo. O diagnóstico precoce é fundamental para o prognóstico da doença. Atualmente, o antígeno específico da próstata (PSA) é o biomarcador mais utilizado; porém, biomarcadores mais específicos devem ser estudados. Objetivo: Avaliar a acurácia da proteína engrenada-2 (EN2) na urina como biomarcador de câncer de próstata. Método: Foi realizada uma busca abrangente no período de janeiro de 2005 a julho de 2016, utilizando as seguintes bases de dados eletrônicas: Medline (PubMed), Embase, Cochrane Library e Lilacs. As palavras-chave utilizadas foram: "engrailed-2", "EN2", "prostatic neoplasms". A busca foi limitada a humanos e não houve restrição de idioma. A avaliação da qualidade dos estudos incluídos foi realizada de acordo com Quadas-2. A análise estatística foi realizada usando o software Meta-DiSc® e RevMan 5.3. Resultados: Foram identificados 248 estudos. Após a triagem dos títulos e resumos, foram excluídos 231. Um total de 17 foram lidos na íntegra e dois, incluídos na metanálise. A sensibilidade combinada foi de 66% (IC95% 0,56-0,75). A especificidade foi de 89% (IC95% 0,86-0,92). O DOR foi de 15,08 (IC95% 8,43-26,97). Conclusão: O teste EN2 mostrou alta especificidade (89%) e baixa sensibilidade (66%).