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2.
Drugs ; 80(13): 1355-1363, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32870481

RESUMO

The antiviral agent remdesivir (Veklury®; Gilead Sciences), nucleotide analogue prodrug, has broad-spectrum activity against viruses from several families. Having demonstrated potent antiviral activity against coronaviruses in preclinical studies, remdesivir emerged as a candidate drug for the treatment of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during the current global pandemic. Phase III evaluation of remdesivir in the treatment of COVID-19 commenced in early 2020 and has thus far yielded promising results. In late May 2020, Taiwan conditionally approved the use of remdesivir in patients with severe COVID-19. This was followed by a rapid succession of conditional approvals in various countries/regions including the EU and Canada. Preceding these conditional approvals, an emergency use authorization for remdesivir had been granted in the USA (on 1 May 2020) and a special approval for emergency use was granted in Japan (on 7 May 2020). This article summarizes the milestones in the development of remdesivir leading to its first conditional approval for the treatment of COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus , Desenvolvimento de Medicamentos , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
4.
Medwave ; 20(7): e7998, 2020 Aug 19.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-32876623

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world causing significant mortality in high risk patients with severe manifestations. To date, Remdesivir has been the only antiviral authorized by FDA as therapy for emergency use. One of the potential complications of this infection is cytokine storm, which optimal treatment remains unknown. We present the case of a 48-year-old man with no past medical history who presented to the hospital with dyspnea, cough, subjective fever, and diarrhea for 10 days. Nasopharyngeal PCR was positive for SARS-CoV-2. His respiratory status rapidly worsened to the point of requiring supplemental oxygen by high flow nasal cannula with FiO2 of 80%. Chest computed tomography showed confluent ground glass opacities in upper lobes accompanied by patchy airspace opacities in lower lobes bilaterally. He was started on hydroxychloroquine, which was switched to Remdesivir when it became available. Then, methylprednisolone was initiated for suspected cytokine storm. The patients oxygenation improved significantly over the following days and he was discharged home with no oxygen supplementation and saturating 96% on room air. Our case illustrates the role of Remdesivir for the treatment of severe COVID-19 pneumonia. We also observed a possible clinical benefit of corticosteroids in the context of suspected cytokine storm. Further studies are needed to evaluate this therapeutic strategy.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico
6.
Ther Innov Regul Sci ; 54(5): 1236-1255, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32865809

RESUMO

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/tratamento farmacológico , Confiabilidade dos Dados , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , China , Comitês de Monitoramento de Dados de Ensaios Clínicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo , Resultado do Tratamento
7.
BMC Med Res Methodol ; 20(1): 206, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32781984

RESUMO

BACKGROUND: The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical perspective, these quantities are challenging to estimate due to episodes being time-dependent and potentially multiple, as well as being determined by the competing, terminal events of discharge alive and death. METHODS: We used multistate models to study COVID-19 patients' time-dependent progress and provide a statistical framework to estimate hazard rates and transition probabilities. These estimates can then be used to quantify average sojourn times of clinically important states such as intensive care and invasive ventilation. We have made two real data sets of COVID-19 patients (n = 24* and n = 53**) and the corresponding statistical code publically available. RESULTS: The expected lengths of intensive care unit (ICU) stay at day 28 for the two cohorts were 15.05* and 19.62** days, while expected durations of mechanical ventilation were 7.97* and 9.85** days. Predicted mortality stood at 51%* and 15%**. Patients mechanically ventilated at the start of the example studies had a longer expected duration of ventilation (12.25*, 14.57** days) compared to patients non-ventilated (4.34*, 1.41** days) after 28 days. Furthermore, initially ventilated patients had a higher risk of death (54%* and 20%** vs. 48%* and 6%**) after 4 weeks. These results are further illustrated in stacked probability plots for the two groups from time zero, as well as for the entire cohort which depicts the predicted proportions of the patients in each state over follow-up. CONCLUSIONS: The multistate approach gives important insights into the progress of COVID-19 patients in terms of ventilation duration, length of ICU stay, and mortality. In addition to avoiding frequent pitfalls in survival analysis, the methodology enables active cases to be analyzed by allowing for censoring. The stacked probability plots provide extensive information in a concise manner that can be easily conveyed to decision makers regarding healthcare capacities. Furthermore, clear comparisons can be made among different baseline characteristics.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Cuidados Críticos/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Respiração Artificial/métodos , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Algoritmos , Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Estudos de Coortes , Ensaios de Uso Compassivo/métodos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Cuidados Críticos/métodos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Teóricos , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
8.
Drug Des Devel Ther ; 14: 3215-3222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821086

RESUMO

The novel coronavirus 2019 (2019-nCoV), formally named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel human infectious coronavirus. The disease caused by SARS-CoV-2 is named COVID-19. Development and manufacturing of specific therapeutics and vaccines to treat COVID-19 are time-consuming processes. At this time, using available conventional therapeutics along with other treatment options may be useful to fight COVID-19. In different clinical trials, efficacy of remdesivir (GS-5734) against Ebola virus has been demonstrated. Moreover, remdesivir may be an effective therapy in vitro and in animal models infected by SARS and MERS coronaviruses. Hence, the drug may be theoretically effective against SARS-CoV-2. Remdesivir is a phosphoramidate prodrug of an adenosine C-nucleoside. By entrance into respiratory epithelial cells in human, the prodrug is metabolized to a nucleoside triphosphate as the active form. The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP). The nucleoside analog is incorporated into the generating RNA strand and causes a delayed stop in the viral replication process. Knowledge about the potential efficacy of remdesivir against coronaviruses has been restricted to in vitro studies and animal models. However, information related to COVID-19 is rapidly growing. Several clinical trials are ongoing for the management of COVID-19 using remdesivir. In this study, characteristics of remdesivir and its usage for treatment of COVID-19 are reviewed based on an electronic search using PubMed and Google Scholar.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/farmacocinética , Alanina/farmacologia , Alanina/uso terapêutico , Animais , Antivirais/farmacocinética , Antivirais/farmacologia , Ensaios Clínicos como Assunto , Humanos , Pandemias , Replicação Viral/efeitos dos fármacos
10.
J Stroke Cerebrovasc Dis ; 29(9): 105095, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807489
11.
BMJ ; 370: m2980, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732190

RESUMO

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation. CONCLUSION: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Respiração Artificial/estatística & dados numéricos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Betacoronavirus/patogenicidade , Centers for Disease Control and Prevention, U.S./estatística & dados numéricos , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Bases de Dados Factuais/estatística & dados numéricos , Combinação de Medicamentos , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/estatística & dados numéricos , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Metanálise em Rede , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Padrão de Cuidado , Resultado do Tratamento , Estados Unidos/epidemiologia
12.
Mol Cell ; 79(5): 710-727, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32853546

RESUMO

The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Genoma Viral , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , RNA Viral/genética , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/uso terapêutico , Amidas/química , Amidas/uso terapêutico , Antivirais/química , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Humanos , Terapia de Alvo Molecular/métodos , Mutação , Pneumonia Viral/virologia , Pirazinas/química , Pirazinas/uso terapêutico , RNA Viral/antagonistas & inibidores , RNA Viral/metabolismo , Ribonucleosídeos/química , Ribonucleosídeos/uso terapêutico , Índice de Gravidade de Doença , Transcrição Genética , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
13.
Mayo Clin Proc ; 95(9): 1946-1954, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32861338

RESUMO

On May 1, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow use of the antiviral drug remdesivir to treat patients with severe coronavirus disease-2019 (COVID-19). Remdesivir is an investigational drug studied in clinical trials for COVID-19 and is available to children and pregnant women through compassionate-use access but is not yet FDA approved. In early May, the US Department of Health and Human Services began to distribute remdesivir, donated by Gilead Sciences, Inc., to hospitals and state health departments for emergency use; multiple shipments have since been distributed. This process has raised questions of how remdesivir should be allocated. The Minnesota Department of Health has collaborated with the Minnesota COVID Ethics Collaborative and multiple clinical experts to issue an Ethical Framework for May 2020 Allocation of Remdesivir in the COVID-19 Pandemic. The framework builds on extensive ethical guidance developed for public health emergencies in Minnesota before the COVID-19 crisis. The Minnesota remdesivir allocation framework specifies an ethical approach to distributing the drug to facilities across the state and then among COVID-19 patients within each facility. This article describes the process of developing the framework and adjustments in the framework over time with emergence of new data, analyzes key issues addressed, and suggests next steps. Sharing this framework and the development process can encourage transparency and may be useful to other states formulating and refining their approach to remdesivir EUA allocation.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/provisão & distribução , Infecções por Coronavirus/tratamento farmacológico , Alocação de Recursos para a Atenção à Saúde/ética , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/provisão & distribução , Alanina/provisão & distribução , Betacoronavirus , Drogas em Investigação/provisão & distribução , Humanos , Minnesota , Pandemias , Estados Unidos , United States Food and Drug Administration
14.
J Int Med Res ; 48(8): 300060520949077, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32842818

RESUMO

The emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Fatores Etários , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Cloroquina/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Reposicionamento de Medicamentos , Humanos , Incidência , Equipamento de Proteção Individual/provisão & distribução , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Quarentena/métodos , Quarentena/organização & administração , Índice de Gravidade de Doença , Distância Social , Análise de Sobrevida
15.
Biochemistry ; 59(33): 3038-3043, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32786401

RESUMO

The COVID-19 pandemic threatens to overwhelm healthcare systems around the world. The only current FDA-approved treatment, which directly targets the virus, is the ProTide prodrug remdesivir. In its activated form, remdesivir prevents viral replication by inhibiting the essential RNA-dependent RNA polymerase. Like other ProTide prodrugs, remdesivir contains a chiral phosphorus center. The initial selection of the (SP)-diastereomer for remdesivir was reportedly due to the difficulty in producing the pure (RP)-diastereomer of the required precursor. However, the two currently known enzymes responsible for the initial activation step of remdesivir are each stereoselective and show differential tissue distribution. Given the ability of the COVID-19 virus to infect a wide array of tissue types, inclusion of the (RP)-diastereomer may be of clinical significance. To help overcome the challenge of obtaining the pure (RP)-diastereomer of remdesivir, we have developed a novel chemoenzymatic strategy that utilizes a stereoselective variant of the phosphotriesterase from Pseudomonas diminuta to enable the facile isolation of the pure (RP)-diastereomer of the chiral precursor for the chemical synthesis of the (RP)-diastereomer of remdesivir.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/síntese química , Monofosfato de Adenosina/síntese química , Alanina/síntese química , Betacoronavirus , Caulobacteraceae/enzimologia , Infecções por Coronavirus , Humanos , Estrutura Molecular , Pandemias , Hidrolases de Triester Fosfórico/química , Pneumonia Viral , RNA Replicase/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos
16.
BMJ ; 370: m2924, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732352

RESUMO

CLINICAL QUESTION: What is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020. CURRENT PRACTICE: Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice. RECOMMENDATIONS: The guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir. HOW THIS GUIDELINE WAS CREATED: An international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems. THE EVIDENCE: The linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay. UNDERSTANDING THE RECOMMENDATION: Most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Fidelidade a Diretrizes , Humanos , Tempo de Internação/estatística & dados numéricos , Metanálise em Rede , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
18.
Emerg Med J ; 37(8): 522-523, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32753375

RESUMO

A short-cut review of the available medical literature was carried out to establish whether remdesivir was an effective treatment for patients with confirmed COVID-19 infection. After abstract review, five papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that despite some recent promising studies, further well-designed and larger trials are needed to answer this specific question.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Adulto , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Resultado do Tratamento
19.
Pharmazie ; 75(8): 407-410, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758342

RESUMO

New drugs against the in COVID-19 pandemic are urgently needed. Gilead Science's remdesivir has been introduced to China through special approval procedures, and was directly conducting the Phase III clinical trial. As expected, the marketing authorization process was completed soon. The drug brought hope to patients as well as business opportunities to companies. However, we must pay attention to the patent competition, generic drug competition and other unfair competition that remdesivir may face in China. China also needs to strengthen the innovation ability and international cooperation ability of local pharmaceutical companies by taking advantages of the opportunity to introduce remdesivir.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/economia , Alanina/administração & dosagem , Alanina/economia , Antivirais/economia , China , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Aprovação de Drogas , Indústria Farmacêutica/economia , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/economia , Competição Econômica , Humanos , Pandemias , Pneumonia Viral/epidemiologia
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