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[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].
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BACKGROUND: Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. METHODS: A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. RESULTS: Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. CONCLUSION: To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Cardiología , Enfermedades Transmisibles , Medicina de Emergencia , Geriatría , Azitromicina , Brasil , COVID-19/terapia , Medicina Comunitaria , Humanos , Inmunización Pasiva , Pacientes Ambulatorios , Procedimientos Quirúrgicos Vasculares , Sueroterapia para COVID-19RESUMEN
Background The Brazilian Football Confederation (CBF) protocol to control the spread of COVID-19 among professional soccer players is based on four cornerstone measures: (1) Tracing all symptomatic and asymptomatic COVID-19 cases by clinical monitoring and nasal swab SARS-CoV-2 RT-PCR testing up to 3 days before the soccer games;(2) Respiratory isolation of all SARS-CoV-2 positive players for at least 10 days, regardless symptoms;(3) All player with clinical suspicion of COVID-19 were immediately quarantined;(4) If a player became SARS-CoV-2 positive after the game, the other players were allowed to play the next game, if they remained asymptomatic and SARS-CoV-2 RT-PCR negative. Understanding how antibody responses to SARS-CoV-2 evolve can provide insights into therapeutic and testing approaches for COVID-19. In the present study we profile the antibody responses of players up to nine months from a SARS-CoV-2 positive RT-PCR test. Methods Serum samples were obtained from 955 soccer players, and analyzed at the same laboratory in São Paulo city, in the Hospital Israelita Albert Einstein. It was used the cPas Technology, the sVNT kit for detecting and measuring circulating neutralizing antibodies against the SARS-CoV-2 virus. Results Neutralizing antibody was positive for 416 samples (416/955=44%;C.I. 95%= [40%;47%]). From the 955 soccer players, 454 had RT-PCR+ previously, up to nine months until the neutralizing antibody tests. From this 454 players, 172 (38%) had neutralizing antibody below 20% (C.I. 95% = [34%;42%]), 30 (7%) between 20% and 30% (C.I. 95% = [5%;9%]), and e 252 (56%) above 30% (C.I. 95% =[51%;60%]). Antibody responses to SARS-CoV-2 were significantly higher in individuals RT-PCR+ (Table 1). There was no difference between the neutralizing antibody responses status to SARS-CoV-2 and the time between the RT-PCR+ and the neutralizing antibody test (p-value = 0.423;Figures 1 and 2, Table 2). Table 1. Neutralizing antibody responses to SARS-CoV-2. Figure 1. Scatter plot with Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Table 2. Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Conclusion This study found neutralizing activity of infection against SARS-CoV-2 in 63% RT-PCR+ individuals, but only in 26% in RT-PCR(-) players. Level of neutralizing antibody responses maintained stable until up to nine months after a RT-PCR+. Figure 2. Percentage of soccer players at each antibody level (below 20%, between 20% and 30%, and above 30%) versus time between the positive RT-PCR test and neutralizing antibody test (days). Disclosures All Authors: No reported disclosures
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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.
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INTRODUCTION: Different therapies are currently used, considered, or proposed for the treatment of COVID-19;for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. METHODS: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. RESULTS: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. CONCLUSION: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients;therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.
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INTRODUCTION: Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. METHODS: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. RESULTS: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. CONCLUSION: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.