RESUMEN
OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice. METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated. RESULTS: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates. CONCLUSION: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.
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Angiotensina I , COVID-19 , Infecciones por Coronavirus , Citocinas , Pulmón , Ratones Endogámicos C57BL , Fragmentos de Péptidos , Animales , Angiotensina I/uso terapéutico , Angiotensina I/farmacología , Fragmentos de Péptidos/uso terapéutico , Fragmentos de Péptidos/farmacología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/virología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/patología , Citocinas/sangre , Ratones , SARS-CoV-2/efectos de los fármacos , Inflamación/tratamiento farmacológico , Carga Viral/efectos de los fármacos , Femenino , Virus de la Hepatitis Murina/efectos de los fármacos , Linfopenia/tratamiento farmacológico , MasculinoRESUMEN
Lipids perform a series of cellular functions, establishing cell and organelles' boundaries, organizing signaling platforms, and creating compartments where specific reactions occur. Moreover, lipids store energy and act as secondary messengers whose distribution is tightly regulated. Disruption of lipid metabolism is associated with many diseases, including those caused by viruses. In this scenario, lipids can favor virus replication and are not solely used as pathogens' energy source. In contrast, cells can counteract viruses using lipids as weapons. In this review, we discuss the available data on how coronaviruses profit from cellular lipid compartments and why targeting lipid metabolism may be a powerful strategy to fight these cellular parasites. We also provide a formidable collection of data on the pharmacological approaches targeting lipid metabolism to impair and treat coronavirus infection.
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Infecciones por Coronavirus , Coronavirus , Humanos , Metabolismo de los Lípidos , Infecciones por Coronavirus/tratamiento farmacológico , Replicación Viral , LípidosRESUMEN
Recently, the U.S. Food and Drug Administration (FDA) approved the first oral antiviral drug to treat mild to moderate cases of coronavirus disease. The combination of nirmatrelvir with an already used protease inhibitor class drug, ritonavir, has led to Paxlovid®. Several studies considered drug repositioning as the first trial for new drugs. The precise identification and quantification of polymorphs in raw materials and finished products are important to researchers involved in pharmaceutical development and quality control processes. In this work, we study the solid-state behavior of the antiretroviral drugs ritonavir and lopinavir in raw materials and in milled compositions. The results indicate that mixtures of ritonavir Forms I and II are found in different batches of raw materials from the same manufacturer; besides three equal crystalline samples, an amorphous batch was found in lopinavir. Furthermore, the milling process of the already amorphous lopinavir seems to facilitate the amorphization of ritonavir as well as the production of some unexpected crystalline forms of ritonavir. A phase transition of ritonavir Form I to Form II is only observed when co-milling with amorphous lopinavir. These findings reveal significant variations in phase purity of raw materials that affect the processing and solid-state properties, representing risks for the product quality.
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Infecciones por Coronavirus , Ritonavir , Humanos , Lopinavir/química , Antivirales , Infecciones por Coronavirus/tratamiento farmacológico , Combinación de MedicamentosRESUMEN
Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.
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Tratamiento Farmacológico de COVID-19 , Infecciones por Coronavirus , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neumonía Viral , Azitromicina/efectos adversos , Brasil/epidemiología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Hidroxicloroquina/efectos adversos , Ivermectina/efectos adversos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiologíaRESUMEN
Background: The urgent need for evidence on measures to respond to the COVID-19 pandemic had led to a rapid escalation in numbers of studies testing potential therapeutic options. The vast amount of data generated by these studies must be interpreted quickly so that physicians have the information to make optimal treatment decisions and manufacturers can scale-up production and bolster supply chains. Moreover, obtaining a quick answer to the question of whether or not a particular intervention is effective can help investigators involved in the many ongoing clinical trials to change focus and pivot to more promising alternatives. It is crucial for healthcare workers to have access to the most up-to-date research evidence to inform their treatment decisions. To address this evidence gap, we compiled the following database of evidence on potential therapeutic options for COVID-19. We hope this information will help investigators, policy makers, and prescribers navigate the flood of relevant data to ensure that management of COVID19, at both individual and population levels, is based on the best available knowledge. We will endeavor to continually update this resource as more research is released into the public space. Summary of evidence: Tables 1 and 2, which divide the total group of identified studies into randomized (Table 1) and non-randomized (Table 2) designs, indicate the primary outcome measures used for each investigation and the level of certainty. Table 3 summarizes the status of evidence for the 193 potential therapeutic options for COVID-19 for which studies were identified through our systematic review.
Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/terapia , COVID-19/tratamiento farmacológico , COVID-19/terapia , TerapéuticaRESUMEN
Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.
No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.
Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.
Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , COVID-19/tratamiento farmacológico , Ivermectina/efectos adversos , Brasil/epidemiología , Azitromicina/efectos adversos , Pandemias , Hidroxicloroquina/efectos adversosRESUMEN
RESUMEN Para potenciar la inmunidad en personas con deterioro gradual del sistema inmune, causado por el envejecimiento o por padecer diferentes comorbilidades, el Grupo de las Industrias Biotecnológica y Farmacéutica de Cuba (BioCubaFarma) ha introducido el producto Biomodulina T. Este se ha utilizado, además, como parte del protocolo de prevención y para el tratamiento de pacientes positivos al SARS-CoV-2. La inmunidad dependiente del timo, incluida la inmunidad de células T y la producción de anticuerpos, disminuye con el tamaño del órgano en los adultos, lo que se conoce como "inmunosenescencia". La Biomodulina T es un extracto diafiltrado de timo de ternera; tiene una acción citorrestauradora e inmunomoduladora, que ha demostrado su eficacia en diferentes grupos de riesgo, dentro de los cuales los ancianos ocupan un lugar especial. En la actual situación epidemiológica nacional e internacional su inclusión en los protocolos de actuación es clave. El uso de este medicamento en un grupo vulnerable, como los ancianos, representa un horizonte esperanzador en tanto se avanza en la producción de vacunas nacionales que sean seguras y eficaces (AU).
ABSTRACT To boost immunity in people with gradual deterioration of the immune system, caused by aging or suffering from different comorbidities, the Group of the Biotechnology and Pharmaceutical Industries of Cuba (Biotechnology Farma) has introduced the product Biomodulin T. This has also been used as part of the prevention protocol and for the treatment of patients positive to SARS-CoV-2. Thymus-dependent immunity, including T-cell immunity and antibody production, decreases with organ size in adults, which is known as "immunosenescence." Biomodulin T is a diafiltered extract of veal thymus; it has a cytorestaurative and immunomodulatory action, which has demonstrated its effectiveness in different risk groups, within which elder people occupy a special place. In the current national and international epidemiological situation its inclusion in the protocols of action is significant. The use of this medication in a vulnerable group, such as elder people, represents a hopeful horizon as progress is made in the production of safe and effective national vaccines (AU).
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Humanos , Masculino , Femenino , Infecciones por Coronavirus/tratamiento farmacológico , Desarrollo de Medicamentos/clasificación , Terapéutica/métodos , Quimioterapia/tendencias , Desarrollo de Medicamentos/métodos , Desarrollo de Medicamentos/organización & administración , Inmunidad/efectos de los fármacosRESUMEN
The term host defense peptides arose at the beginning to refer to those peptides that are part of the host's immunity. Because of their broad antimicrobial capacity and immunomodulatory activity, nowadays, they emerge as a hope to combat resistant multi-drug microorganisms and emerging viruses, such as the case of coronaviruses. Since the beginning of this century, coronaviruses have been part of different outbreaks and a pandemic, and they will be surely part of the next pandemics, this review analyses whether these peptides and their derivatives are ready to be part of the treatment of the next coronavirus pandemic.
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Péptidos Catiónicos Antimicrobianos/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Pandemias , Antiinflamatorios/síntesis química , Antiinflamatorios/inmunología , Antiinflamatorios/uso terapéutico , Péptidos Catiónicos Antimicrobianos/síntesis química , Péptidos Catiónicos Antimicrobianos/inmunología , Antivirales/síntesis química , Antivirales/inmunología , Ensayos Clínicos como Asunto , Coronavirus/efectos de los fármacos , Coronavirus/fisiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Humanos , Inmunomodulación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virologíaRESUMEN
OBJETIVO: Investigar manifestações clínicas, fatores de risco, tratamento e prevenção em recém-nascidos acometidos pela COVID-19 relatados na literatura científica. MÉTODO: Revisão integrativa realizada no mês de maio de 2020, nas bases de dados LILACS, MEDLINE e Biblioteca Virtual em Saúde, por meio de combinações entre os termos controlados newborn, COVID-19, SARS-CoV-2. RESULTADOS: Sete estudos compuseram a amostra final, sendo cinco publicações provenientes da China, onde foram relatados os primeiros casos de infecção neonatal. DISCUSSÃO: A prática baseada em evidências é fundamental para o cuidado ao recém-nascido diante do atual contexto pandêmico. Assim, atualizações sobre abordagens terapêuticas são necessárias. CONCLUSÃO: Medidas de prevenção são importantes, visto que existem lacunas relacionadas ao tratamento da COVID-19 em recém-nascidos. As manifestações clínicas podem variar desde sintomas respiratórios até gastrointestinais e cutâneos. Embora os casos relatados pareçam ser adquiridos no período pós-natal, faz-se necessário mais estudos e evidências para elucidar o risco de transmissão vertical.
OBJECTIVE: To investigate clinical manifestations, risk factors, treatment, and prevention of newborns affected by COVID-19 reported in the scientific literature. METHOD: This was an integrative review carried out in May 2020 in the LILACS, MEDLINE, and Virtual Health Library databases, via the combination of the controlled terms newborn, COVID-19, SARS-CoV-2. RESULTS: Seven studies composed the final sample, five of which were from China, where the first cases of neonatal infection were reported. DISCUSSION: Evidence-based practice is essential for neonatal care in light of the current pandemic context, which requires constant updates about therapeutic approaches. CONCLUSION: Prevention measures are important, because there are gaps related to COVID-19 treatment in newborns. Clinical manifestations can vary from respiratory symptoms to gastrointestinal and cutaneous symptoms. Although the cases reported seem to have been acquired in the postnatal period, more studies and evidence are needed to clarify the risk of vertical transmission.
OBJETIVO: Investigar las manifestaciones clínicas, factores de riesgo, tratamiento y prevención de recién nacidos infectados por COVID-19 informados en la literatura científica. MÉTODO: Revisión integrativa realizada en mayo de 2020 en bases de datos LILACS, MEDLINE y Biblioteca Virtual en Salud, utilizándose combinaciones entre los términos controlados newborn, COVID-19, SARS-CoV-2. RESULTADOS: Muestra final integrada por siete estudios, cinco de ellos publicaciones de China, donde se reportaron los primeros casos de infección neonatal. DISCUSIÓN: La práctica basada en evidencias es fundamental para el cuidado del recién nacido ante el contexto pandémico actual. Las actualizaciones sobre abordajes terapéuticos resultan necesarias. CONCLUSIÓN: Las medidas preventivas son importantes, considerando existencia de brechas para tratamiento de la COVID-19 en recién nacidos. Las manifestaciones clínicas varían desde síntomas respiratorios hasta gastrointestinales y cutáneos. Aunque los casos reportados remiten a infección en período posnatal, son necesarios más estudios y evidencias para determinar el riesgo de transmisión vertical.
Asunto(s)
Humanos , Recién Nacido , Salud Infantil , Factores de Riesgo , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/tratamiento farmacológicoRESUMEN
Desde os primeiros surtos da doença provocada pelo novo coronavírus (SARS-CoV-2), que se disseminou rapidamente pelo mundo, há um interesse crescente em encontrar um potencial agente terapêutico para a doença. A prática atual para tratar COVID-19 é variável, o que reflete a incerteza em grande escala e, para tentar sanar essa incerteza, numerosos ensaios clínicos randomizados de diferentes medicamentos estão em andamento com o intuito de melhor orientar a clínica (WHO,2020). Até o momento os trabalhos acerca do uso do ganciclovir para tratar pacientes que contraíram a doença são escassos e ainda não foram realizados ensaios clínicos com este fármaco, apenas relatos e séries de caso foram localizados na literatura. Considerando os estudos analisados e a pirâmide de evidência proposta pelo Oxford Center for Evidence-Based Medicine (figura 02), ainda não existe evidência robusta para sustentar a utilização deste fármaco, em larga escala, no tratamento da COVID-19.
Since the first outbreaks of the disease caused by the new coronavirus (SARS-CoV-2), which has spread rapidly around the world, there is a growing interest in finding a potential therapeutic agent for the disease. The current practice to treat COVID-19 is variable, which reflects large-scale uncertainty and, to try to address this uncertainty, numerous randomized clinical trials of different drugs are underway in order to better guide the clinic (WHO,2020). To date, studies on the use of ganciclovir to treat patients who contracted the disease are scarce and no clinical trials have been conducted with this drug, only reports and case series have been found in the literature. Considering the studies analyzed and the pyramid of evidence proposed by the Oxford Center for Evidence-Based Medicine (figure 02), there is still no robust evidence to support the use of this drug, on a large scale, in the treatment of COVID-19.
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Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Ganciclovir/administración & dosificación , Ganciclovir/efectos adversos , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/tratamiento farmacológicoRESUMEN
The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.
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Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Ivermectina/farmacología , Animales , Antivirales/administración & dosificación , Peso Corporal/efectos de los fármacos , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Femenino , Ivermectina/administración & dosificación , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Virus de la Hepatitis Murina/patogenicidad , Neutrófilos/efectos de los fármacos , Proteínas/metabolismo , Transaminasas/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Carga Viral/efectos de los fármacosRESUMEN
CONTEXTE: Le présent document ainsi que les constats qu'il énonce ont été rédigés dans le contexte de la crise sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. L'objectif est de réaliser une recension des données publiées et de mobiliser les savoirs clés afin d'informer les décideurs publics et les professionnels de la santé et des services sociaux. Bien que les constats reposent sur un repérage exhaustif des données scientifiques publiées, l'évaluation de la qualité méthodologique des études et une appréciation du niveau de preuve scientifique par paramètre clinique d'intérêt, le processus ne repose pas sur une méthode systématique ni une validation externe selon les normes habituelles à l'INESSS. Par ailleurs, les positions ne découlent pas d'un processus de consultation élaboré. Dans les circonstances d'une telle crise de santé publique, l'INESSS reste à l'affût de toutes nouvelles données, qu'elles soient de nature scientifique ou contextuelle, susceptibles de lui faire modifier cette réponse. MÉTHODOLOGIE: Questions d'évaluation Comparativement aux standards de soins, est-ce qu'un supplément de vitamine D, chez les personnes ayant ou non une déficience ou une insuffisance, est efficace et sécuritaire pour, prévenir l'infection et les manifestations cliniques de la COVID-19? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce n'exige pas une hospitalisation? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce exige o une hospitalisation sans le recours à une oxygénothérapie; o une hospitalisation avec le recours à une oxygénothérapie non invasive (oxygène à faible débit, à haut débit, ventilation mécanique non invasive); o une hospitalisation avec le recours à une oxygénothérapie invasive (ventilation mécanique invasive, ECMO)? Quelle est la position des sociétés savantes, des agences règlementaires, des agences de santé publique et des agences d'évaluation des technologies en santé sur l'usage d'un supplément de vitamine D dans la prévention et le traitement de la COVID-19? Type de revue de littérature: Revue rapide. RÉSULTATS: ÉTAT ACTUEL DES CONNAISSANCES SCIENTIFIQUES. Données cliniques sur l'efficacité de la supplémentation en vitamine D dans le contexte de la COVID-19. Depuis l'instauration en mars 2020 de la recherche systématique en continu de la littérature scientifique sur les médicaments à visée thérapeutique, 42 027 notices ont été recensées dont 113 études cliniques où l'intervention étudiée portait sur la vitamine D. De ce nombre, 3 ECRA [Murai et al., 2021; Castillo et al., 2020; Rastogi et al., 2020] ont été retenus. Ces études sont décrites ci-dessous en fonction du type de prise en charge, soit la prophylaxie pré/post-exposition, ou le traitement de patient dont l'état de santé requiert ou non une hospitalisation. Seuls les paramètres d'intérêts sur l'évolution de la charge virale, l'amélioration ou la résolution des symptômes ou d'évolution clinique, le pronostic, l'innocuité ou la mortalité sont présentés. Supplémentation en vitamine D en prophylaxie: En date du 24 février 2021, aucun ECRA ni aucune étude observationnelle publiés n'ont été retracés par la recherche de la littérature scientifique sur les bénéfices cliniques associés à l'usage de vitamine D en prophylaxie pré- ou post- exposition au SARS-CoV-2. Par contre, il y a quelques essais cliniques actuellement enregistrés sur le site de ClinicalTrials, dont un essai comparatif à répartition aléatoire multicentrique à triple insu (PROTECT6 ) en cours de réalisation au sein de deux hôpitaux du Québec. Le principal objectif de cet essai est d'étudier les effets prophylactiques d'une supplémentation à hautes doses de vitamine D3 per os (bolus 100 000 UI suivi de 10 000 UI par semaine pendant 16 semaines) chez les travailleurs de la santé exposés à la COVID-19. Il est prévu que l'essai se termine en juin 2021. DISCUSSION: Au terme des travaux, il ressort qu'aucun ECRA ni aucune étude observationnelle publiés dans la littérature ne permettent d'évaluer l'effet d'une supplémentation en vitamine D utilisée en prophylaxie pré- ou post- exposition au SRAS-CoV-2 ni dans le traitement des sujets COVID-19 confirmés dont l'état n'exige pas une hospitalisation. Toutefois, en ce qui concerne les personnes atteintes de la COVID-19 dont l'état de santé requiert une hospitalisation, l'état actuel des connaissances scientifiques suggère qu'une supplémentation en vitamine D3 ne permet pas de réduire la durée d'hospitalisation et le nombre de nouveaux sujets ayant besoin de ventilation mécanique invasive et ne permet pas d'établir un lien en une supplémentation en vitamine D et les admissions aux soins intensifs ou la mortalité. Un supplément en vitamine D3 à raison de 60 000 UI par jour pendant 8 ou 14 jours, chez des personnes ayant une déficience en vitamine D, pourrait cependant permettre d'augmenter la proportion de sujets avec une négativation de la RTPCR sans toutefois avoir d'impact sur la durée moyenne avant la négativation de celle-ci. Il est toutefois important de souligner que les trois ECRA ont été réalisés sur des populations distinctes, hospitalisées pour une COVID-19 de sévérité variable, et avec différentes posologies et formes de vitamine D3 (calcifédiol ou cholécalciférol). Les profils d'innocuité et d'interactions médicamenteuses de la vitamine D sont aujourd'hui bien connus dans plusieurs contextes extérieurs à la COVID-19 [Euro-Pharm International Canada, 2018; Vifor Pharma, 2018]. Fondé sur 2 ECRA à double insu conduits au Brésil et en Inde dans le contexte de la COVID-19, la supplémentation de vitamine D3 à haute dose semble sécuritaire lorsque cette dernière est administrée en prise unique ou de manière quotidienne pendant une durée maximale de 14 jours chez des sujets adultes atteints de la COVID-19 et hospitalisés. Dans tous les documents consultés présentant des positions ou des recommandations cliniques, aucune organisation ne se prononce en faveur de l'usage de la vitamine D en prévention d'une infection par le SARS-CoV-2 ou comme traitement d'une telle infection en dehors d'un essai clinique, en raison d'une insuffisance de preuves. Compte tenu des risques potentiels d'effets indésirables, un suivi régulier des personnes recevant des doses de vitamine D supérieures à 4 000 UI par jour est également recommandé. Cette réponse rapide de l'INESSS comporte certaines limites qui méritent d'être soulignées. D'abord, l'analyse du niveau de preuve scientifique est basée sur 3 études primaires de type ECRA, elles aussi, empreintes de biais et de limites méthodologiques (y compris des déséquilibres dans les caractéristiques des sujets, dans la puissance statistique et dans les posologies et formes de vitamine D3 utilisées) affectant la confiance envers les résultats actuellement disponibles. Par ailleurs, le manque de résultats ne permet pas de conclure quant à d'éventuelles différences d'efficacité entre des sujets à différents stades de la maladie ou avec des niveaux de vitamine D différents au début des études (taux normal, insuffisance, déficience). Enfin, les constats ne découlent pas d'un processus de consultation élaboré. À la suite de l'analyse effectuée, la tendance pointe vers une absence de bénéfice de la supplémentation en vitamine D ayant 2021-03-08 15:16 22 un réel impact sur l'évolution clinique ou la mortalité liée à la COVID-19. Il faudra toutefois attendre les résultats d'ECRA supplémentaires dont la qualité méthodologique sera jugée acceptable avant d'infirmer ou confirmer une absence de bénéfices. L'efficacité et l'innocuité d'une supplémentation en vitamine D sont présentement évaluées dans plusieurs études cliniques en cours, soit en prophylaxie, chez des patients non hospitalisés ou chez des patients hospitalisés9 . En demeurant à l'affût de nouvelles données scientifiques, cette réponse rapide permet d'informer les professionnels de la santé et de les soutenir dans leur prise de décision clinique dans le contexte de la pandémie actuelle.
Asunto(s)
Humanos , Neumonía Viral/prevención & control , Neumonía Viral/tratamiento farmacológico , Vitamina D/administración & dosificación , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/tratamiento farmacológico , Evaluación de la Tecnología Biomédica , Análisis Costo-EficienciaRESUMEN
Uma resposta a ser alcançada durante a pandemia da COVID-19 é qual terapia medicamentosa a ser utilizada de forma exitosa e sem comprometer a saúde do paciente. Desde o surgimento dos primeiros casos, cientistas do mundo inteiro têm elaborado estudos de novos medicamentos ou de reaproveitamento de medicamentos que combata o vírus da COVID-19 ou, pelo menos, minimize os danos causados pela doença. No entanto, mesmo após vários estudos, os cientistas estão divididos entre aqueles que apoiam o uso de determinados fármacos para impedir o agravamento da doença ou até mesmo a contaminação pelo vírus (o chamado "kit-covid") e aqueles que afirmam ser uma falácia o uso de tais medicamentos e que o uso dos mesmos pode inclusive comprometer ainda mais a saúde do paciente.
One response to be achieved during the COVID-19 pandemic is which drug therapy to be used successfully and without compromising the patient's health. Since the emergence of the first cases, scientists around the world have been researching new drugs or reusing drugs that fight the COVID-19 virus or at least minimize the damage caused by the disease. However, even after several studies, scientists are divided between those who support the use of certain drugs to prevent the worsening of the disease or even contamination by the virus (the so-called "kit-covid") and those who claim to be a fallacy the use of such drugs and that the use of them can even further compromise the health of the patient.