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1.
J Infect Chemother ; 27(1): 94-98, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32988730

RESUMEN

The effect of systemic corticosteroids on clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains controversial. While the use of corticosteroids raises concerns regarding delayed viral clearance, secondary infections, and long-term complications that can lead to increased mortality, corticosteroids have the potential to reduce mortality if used appropriately. Herein, we report good outcomes in two patients with COVID-19 who received systemic corticosteroids as adjunctive therapy. An 83-year-old man with hypertension and smoking history and a 62-year-old man with a drinking habit were transferred to our hospital with a diagnosis of COVID-19. The patients developed general malaise and loss of appetite with persistent high fever. Despite the prescription of antiviral drugs, their hypoxemia progressed rapidly. However, after the introduction of systemic corticosteroids, their symptoms improved as the fever decreased, and their hypoxemia gradually improved. These results suggest that some patients with COVID-19 may benefit from the appropriate use of systemic corticosteroids as adjunctive therapy.


Asunto(s)
Corticoesteroides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/epidemiología , Antivirales/uso terapéutico , Betacoronavirus , Terapia Combinada , Infecciones por Coronavirus/epidemiología , Humanos , Hipertensión/epidemiología , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Fumar/epidemiología , Neoplasias Gástricas/epidemiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
2.
J Infect Chemother ; 27(1): 99-102, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33023821

RESUMEN

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Neoplasias/complicaciones , Neumonía Viral/tratamiento farmacológico , Ritonavir/uso terapéutico , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamiento farmacológico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Brotes de Enfermedades , Quimioterapia Combinada , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/tratamiento farmacológico , Resultado Fatal , Humanos , Italia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Ann Med ; 53(1): 117-134, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33095083

RESUMEN

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.


Asunto(s)
Antimaláricos/uso terapéutico , Cardiotoxicidad/etiología , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antimaláricos/farmacología , Ensayos Clínicos como Asunto , Humanos , Hidroxicloroquina/farmacología , Pandemias
4.
Acta Pharm ; 71(2): 163-174, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33151166

RESUMEN

The current outbreak of novel coronavirus (COVID-19) infections urges the need to identify potential therapeutic agents. Therefore, the repurposing of FDA-approved drugs against today's diseases involves the use of de-risked compounds with potentially lower costs and shorter development timelines. In this study, the recently resolved X-ray crystallographic structure of COVID-19 main protease (Mpro) was used to generate a pharmacophore model and to conduct a docking study to capture antiviral drugs as new promising COVID-19 main protease inhibitors. The developed pharmacophore successfully captured five FDA-approved antiviral drugs (lopinavir, remdesivir, ritonavir, saquinavir and raltegravir). The five drugs were successfully docked into the binding site of COVID-19 Mpro and showed several specific binding interactions that were comparable to those tying the co-crystallized inhibitor X77 inside the binding site of COVID-19 Mpro. Three of the captured drugs namely, remdesivir, lopinavir and ritonavir, were reported to have promising results in COVID-19 treatment and therefore increases the confidence in our results. Our findings suggest an additional possible mechanism of action for remdesivir as an antiviral drug inhibiting COVID-19 Mpro. Additionally, a combination of structure-based pharmacophore modeling with a docking study is expected to facilitate the discovery of novel COVID-19 Mpro inhibitors.


Asunto(s)
Infecciones por Coronavirus/enzimología , Neumonía Viral/enzimología , Inhibidores de Proteasas/farmacología , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/química , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/química , Alanina/farmacología , Alanina/uso terapéutico , Antivirales/química , Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Cristalografía por Rayos X , Descubrimiento de Drogas/métodos , Reposicionamiento de Medicamentos , Humanos , Modelos Químicos , Simulación del Acoplamiento Molecular , Estructura Molecular , Pandemias , Neumonía Viral/tratamiento farmacológico , Inhibidores de Proteasas/química , Relación Estructura-Actividad
5.
Acta Pharm ; 71(2): 175-184, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33151168

RESUMEN

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Dipeptidil Peptidasa 4/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Biología Computacional , Infecciones por Coronavirus/complicaciones , Cristalografía por Rayos X , Minería de Datos , Complicaciones de la Diabetes/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Reposicionamiento de Medicamentos , Redes Reguladoras de Genes , Humanos , Estructura Molecular , Pandemias , Neumonía Viral/complicaciones
6.
J Ethnopharmacol ; 265: 113319, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32882361

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the outbreaks such as SARS, bird flu and swine flu, which we frequently encounter in our century, we need fast solutions with no side effects today more than ever. Due to having vast ethnomedical experience and the richest flora (34% endemic) of Europe and the Middle East, Turkey has a high potential for research on this topic. Plants that locals have been using for centuries for the prevention and treatment of influenza can offer effective alternatives to combat this problem. In this context, 224 herbal taxa belonging to 45 families were identified among the selected 81 studies conducted in the seven regions of Turkey. However, only 35 (15.6%) of them were found to be subjected to worldwide in vitro and in vivo research conducted on anti-influenza activity. Quercetin and chlorogenic acid, the effectiveness of which has been proven many times in this context, have been recorded as the most common (7.1%) active ingredients among the other 56 active substances identified. AIM OF THE STUDY: This study has been carried out to reveal the inventory of plant species that have been used in flu treatment for centuries in Turkish folk medicine, which could be used in the treatment of flu or flu-like pandemics, such as COVID 19, that humanity has been suffering with, and also compare them with experimental studies in the literature. MATERIALS AND METHODS: The investigation was conducted in two stages on the subject above by using electronic databases, such as Web of Science, Scopus, ScienceDirect, ProQuest, Medline, Cochrane Library, EBSCO, HighWire Press, PubMed and Google Scholar. The results of both scans are presented in separate tables, together with their regional comparative analysis. RESULTS: Data obtained on taxa are presented in a table, including anti-influenza mechanism of actions and the active substances. Rosa canina (58.7%) and Mentha x piperita (22.2%) were identified as the most common plants used in Turkey. Also, Sambucus nigra (11.6%), Olea europaea (9.3%), Eucalyptus spp., Melissa officinalis, and Origanum vulgare (7.0%) emerged as the most investigated taxa. CONCLUSION: This is the first nationwide ethnomedical screening work conducted on flu treatment with plants in Turkey. Thirty-nine plants have been confirmed in the recent experimental anti-influenza research, which strongly shows that these plants are a rich pharmacological source. Also, with 189 (84.4%) taxa, detections that have not been investigated yet, they are an essential resource for both national and international pharmacological researchers in terms of new natural medicine searches. Considering that the production of antimalarial drugs and their successful use against COVID-19 has begun, this correlation was actually a positive and remarkable piece of data, since there are 15 plants, including Centaurea drabifolia subsp. Phlocosa (an endemic taxon), that were found to be used in the treatment of both flu and malaria.


Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus , Etnofarmacología/métodos , Gripe Humana/tratamiento farmacológico , Pandemias , Plantas Medicinales/clasificación , Neumonía Viral , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Humanos , Medicina Tradicional/métodos , Fitoterapia , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Turquia
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118825, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32866803

RESUMEN

Novel antiviral active molecule 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl)acetamide has been synthesised and characterized by FT-IR and FT-Raman spectra. The equilibrium geometry, natural bond orbital calculations and vibrational assignments have been carried out using density functional B3LYP method with the 6-311G++(d,p) basis set. The complete vibrational assignments for all the vibrational modes have been supported by normal coordinate analysis, force constants and potential energy distributions. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces. Drug likeness has been carried out based on Lipinski's rule and the absorption, distribution, metabolism, excretion and toxicity of the title molecule has been calculated. Antiviral potency of 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro-phenyl) acetamide has been investigated by docking against SARS-CoV-2 protein. The optimized geometry shows near-planarity between the phenyl ring and the pyrimidine ring. Differences in the geometries due to the substitution of the most electronegative fluorine atom and intermolecular contacts due to amino pyrimidine were analyzed. NBO analysis reveals the formation of two strong stable hydrogen bonded N-H···N intermolecular interactions and weak intramolecular interactions C-H···O and N-H···O. The Hirshfeld surfaces and consequently the 2D-fingerprint confirm the nature of intermolecular interactions and their quantitative contributions towards the crystal packing. The red shift in N-H stretching frequency exposed from IR substantiate the formation of N-H···N intermolecular hydrogen bond. Drug likeness and absorption, distribution, metabolism, excretion and toxicity properties analysis gives an idea about the pharmacokinetic properties of the title molecule. The binding energy -8.7 kcal/mol of the nonbonding interaction present a clear view that 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl) acetamide can irreversibly interact with SARS-CoV-2 protease.


Asunto(s)
Antivirales/química , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Inhibidores de Proteasas/química , Proteínas no Estructurales Virales/antagonistas & inhibidores , Antivirales/farmacocinética , Betacoronavirus/enzimología , Cristalografía por Rayos X , Cisteína Endopeptidasas , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Dinámicas no Lineales , Inhibidores de Proteasas/farmacocinética , Conformación Proteica , Teoría Cuántica , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Termodinámica , Vibración
8.
Ars pharm ; 61(4): 253-257, oct.-dic. 2020. tab
Artículo en Español | IBECS | ID: ibc-193586

RESUMEN

INTRODUCCIÓN: La Enfermedad por coronavirus 2019 (COVID-19) causada por el virus SARS-CoV-2, con característica de infectar el tracto respiratorio causando un síndrome respiratorio agudo como paso inicial para ingresar a la célula huésped el virus usa los receptores ACE II y la proteína transmembrana TMPRSS2 para causar la infección, Por lo que se ha descrito diferentes tipos de fármacos para realizar su inhibición en la adhesión del paso inicial. METODOLOGÍA: Revisión no sistemática de artículos con la ayuda de palabras clave preestablecidas. RESULTADOS: En esta revisión presentaremos fármacos que inhiben este tipo de receptor, por lo tanto, estos medicamentos podrían considerarse candidatos potenciales para mitigar la propagación del SARS-CoV-2


INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus with characteristic of infecting the respiratory tract, causing severe acute respiratory syndrome. The virus uses the ACE II receptors and the transmembrane protein TMPRSS2 initial step to enter the host cell, this contribution described different types of drug, to perform its inhibition in initial step adhesion. METHODOLOGY: Non-systematic review of articles with the help of preset keywords. RESULTS: In this review we will present drugs that inhibitors of this type of receptor therefore these drugs could be considered potential candidates to mitigate the spread of SARS-CoV-2


Asunto(s)
Humanos , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Serina Endopeptidasas/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de Serina Proteinasa/farmacología , Serina Endopeptidasas/farmacología
9.
PLoS One ; 15(11): e0241947, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33166346

RESUMEN

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose the protocol described below to perform an individual-patient data (IPD) network meta-analysis (NMA) in order to evaluate the efficacies of different antiviral drugs to treat patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We will search the Medline, EMBASE, Cochrane Library, SinoMed, CNKI and VIP databases from their inceptions through July 2020. There will be no restrictions on language, publication year, or publication type. Randomized clinical trials (RCTs) and prospective cohort studies with antiviral treatments for COVID-19 will be considered. Two reviewers will independently select studies and collect data. Risk-of-bias assessments will be completed using the Cochrane risk-of-bias scale. Primary outcome will be the COVID-19 recovery rate. We will combine aggregated data from IPD with the NMA in a single model, compare the effects of different antiviral drugs on patient-relevant efficacy, and rank the results to decide which is the most effective. TRIAL REGISTRATION: PROSPERO registration number: CRD42020167038.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Bases de Datos Factuales , Humanos , Metaanálisis en Red , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/patología , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Resultado del Tratamiento
10.
Acta Biomed ; 91(13-S): e2020008, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33170174

RESUMEN

BACKGROUND AND AIM: The recent COVID-19 pandemic caused by SARS-CoV-2 affected more than six million people and caused thousands of deaths. The lack of effective drugs or vaccines against SARS-CoV-2 further worsened the situation. This review is focused on the identification of molecules that may inhibit viral entry into host cells by endocytosis. METHODS: We performed the literature search for these natural compounds in the articles indexed in PubMed. RESULTS: Natural products against viral infections have been gaining importance in recent years. Specific natural compounds like phytosterols, polyphenols, flavonoids, citrus, galangal, curcuma and hydroxytyrosol are being analyzed to understand whether they could inhibit SARS-CoV-2. CONCLUSIONS: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus , Factores Biológicos/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Endocitosis/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Humanos , Pandemias
11.
Acta Biomed ; 91(13-S): e2020009, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33170175

RESUMEN

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. METHODS: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. RESULTS: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.


Asunto(s)
Antivirales/efectos adversos , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Endocitosis/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Neumonía Viral/tratamiento farmacológico , alfa-Ciclodextrinas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Células CACO-2 , Técnicas de Cultivo de Célula , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vaporizadores Orales , Pandemias , Alcohol Feniletílico/efectos adversos , Proyectos Piloto , Adulto Joven
12.
J Thromb Haemost ; 18(11): 3099-3105, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33174388

RESUMEN

BACKGROUND: Observational studies indicate that children hospitalized with COVID-19-related illness, like adults, are at increased risk for venous thromboembolism (VTE). A multicenter phase 2 clinical trial of anticoagulant thromboprophylaxis in children hospitalized with COVID-19-related illness has recently been initiated in the United States. To date, there remains a paucity of high-quality evidence to inform clinical practice world-wide. Therefore, the objective of this scientific statement is to provide consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses, and to identify priorities for future research. METHODS: We surveyed 20 pediatric hematologists and pediatric critical care physicians from several continents who were identified by Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee leadership as having experience and expertise in the use of anticoagulant thromboprophylaxis and/or the management of COVID-19-related illness in children. A comprehensive review of the literature on COVID-19 in children was also performed. RESULTS: Response rate was 90%. Based on consensus of expert opinions, we suggest the administration of low-dose low molecular weight heparin subcutaneously twice-daily as anticoagulant thromboprophylaxis (in the absence of contraindications, and in combination with mechanical thromboprophylaxis with sequential compression devices, where feasible) in children hospitalized for COVID-19-related illness (including the multisystem inflammatory syndrome in children [MIS-C]) who have markedly elevated D-dimer levels or superimposed clinical risk factors for hospitalassociated VTE. For children who are clinically unstable or have severe renal impairment, we suggest the use of unfractionated heparin by continuous intravenous infusion as anticoagulant thromboprophylaxis. In addition, continued efforts to characterize VTE risk and risk factors in children with COVID-19, as well as to evaluate the safety and efficacy of anticoagulant thromboprophylaxis strategies in children hospitalized with COVID-19-related illness (including MIS-C) via cooperative multicenter trials, were identified among several key priorities for future research. CONCLUSION: These consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses and priorities for future research will be updated as high-quality evidence emerges.


Asunto(s)
Anticoagulantes/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Medicina Basada en la Evidencia/normas , Hospitalización , Neumonía Viral/tratamiento farmacológico , Investigación/normas , Tromboembolia Venosa/prevención & control , Adolescente , Factores de Edad , Anticoagulantes/efectos adversos , Niño , Preescolar , Toma de Decisiones Clínicas , Consenso , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Encuestas de Atención de la Salud , Humanos , Pandemias , Neumonía Viral/sangre , Neumonía Viral/complicaciones , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Adulto Joven
13.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33138181

RESUMEN

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.


Asunto(s)
Lesión Pulmonar Aguda/patología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/patología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/patología , Síndrome Respiratorio Agudo Grave/patología , Vasoconstricción/fisiología , Betacoronavirus , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/patología , Sistema Calicreína-Quinina/fisiología , Pandemias , Sistema Renina-Angiotensina/fisiología , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Vasoconstricción/efectos de los fármacos
14.
Pan Afr Med J ; 35(Suppl 2): 134, 2020.
Artículo en Francés | MEDLINE | ID: mdl-33193949

RESUMEN

Hydroxychloroquine is an agent used as a treatment but also considered as a prophylaxis for SARS-CoV-2 infection. We report the case of a patient who developed COVID-19 while on hydroxychloroquine for mixed connectivitis associated with spondyloarthritis. Although more work is needed before any conclusions can be drawn, this raises questions about the protective role of this drug against infection. Are they really protected against COVID-19 or will they develop pauci-symptomatic forms?


Asunto(s)
Antirreumáticos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Etanercept/uso terapéutico , Hidroxicloroquina/uso terapéutico , Enfermedad Mixta del Tejido Conjuntivo/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Enfermedades Cutáneas Virales/etiología , Espondiloartropatías/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Urticaria/etiología , Antirreumáticos/efectos adversos , Infecciones por Coronavirus/complicaciones , Susceptibilidad a Enfermedades , Etanercept/efectos adversos , Humanos , Masculino , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Pandemias , Neumonía Viral/complicaciones , Espondiloartropatías/complicaciones , Factor de Necrosis Tumoral alfa/efectos adversos , Adulto Joven
15.
Pan Afr Med J ; 35(Suppl 2): 136, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33193951

RESUMEN

Introduction: SARS-CoV-2 is an emerging health threat outbreak. It may cause severe viral pneumonia with Acute Respiratory Distress Syndrome requiring critical care. Aim: to describe clinical features and outcomes of critically ill patients with SARS-CoV-2 infection. Methods: it was a retrospective study carried out in the medical ICU of Farhat Hached teaching hospital between March 11 and May 7, 2020. All consecutive patients with RT-PCR confirmed COVID-19 were included. Clinical characteristics and outcomes were collected by reviewing medical records. Results: during the study period, 10 critically ill patients with COVID-19 were enrolled. Mean age, 51.8±6.3 years; 8(80%), male. The most common comorbidities were; diabetes mellitus, 6(60%), obesity 2(20%), chronic kidney disease 2(20%) and hypertension 1(10%). Mean SAPS II, 23.2±1.8. The mean arterial oxygen partial pressure to fractional inspired oxygen ratio at admission was 136.2±79.7. Noninvasive mechanical ventilation was used in 4(40%) patients and 7(70%) received invasive mechanical ventilation. Tidal volume and PEEP were set respectively within the median [IQR] of, 5.7[5.6-6.3]ml/Kg and 10.7[6.5-11.7]cm H2O. Plateau pressure was monitored in the median [IQR] of 27.9 [25.9-28.5] cm H2O. Four patients received hydroxychloroquine alone and five hydroxychloroquine associated with an antiviral. Five patients developed respectively hyperactive (n=2), hypoactive (n=2) and mixed delirium (n=1). Mortality rate was at 70%. Conclusion: this study demonstrated a particular profile of COVID-19 in the critically ill as a severe presentation in aged males with comorbidities presenting with an ARDS-like and neurological impairment with poor prognosis. The only survivals seem to have benefited from noninvasive ventilatory support.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Enfermedad Crítica/epidemiología , Neumonía Viral/epidemiología , Antivirales/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Infecciones por Coronavirus/tratamiento farmacológico , Delirio/etiología , Diabetes Mellitus/epidemiología , Femenino , Mortalidad Hospitalaria , Hospitales de Enseñanza/estadística & datos numéricos , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Pandemias , Neumonía Viral/tratamiento farmacológico , Pronóstico , Insuficiencia Renal Crónica/epidemiología , Respiración Artificial/estadística & datos numéricos , Síndrome de Dificultad Respiratoria del Adulto/etiología , Estudios Retrospectivos , Puntuación Fisiológica Simplificada Aguda , Túnez/epidemiología
16.
Pan Afr Med J ; 35(Suppl 2): 149, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33193964

RESUMEN

HIV/AIDS is an infectious disease that has claimed the lives of millions of people worldwide. Currently, there is no vaccine that has been developed in a bid to fight this deadly infection, however, antiretrovirals (ARVs), which are drugs used in the treatment of HIV infection are routinely prescribed to infected persons. They act via several mechanisms of action to reduce the severity of infection and rate of infectivity of the virus by decreasing the viral load while increasing CD4 counts. COVID-19 pandemic has resulted in unprecedented events affecting almost all areas of humans' life including availability of medicines and other consumables. This paper analyses the availability of ARVs during COVID-19 era and offered recommendations to be adopted in order to prevent shortages.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Infecciones por VIH/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/provisión & distribución , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/economía , Antirretrovirales/provisión & distribución , Terapia Antirretroviral Altamente Activa/economía , Betacoronavirus , Infecciones por Coronavirus/economía , Infecciones por Coronavirus/epidemiología , Países en Desarrollo , Costos de los Medicamentos/tendencias , Industria Farmacéutica , Infecciones por VIH/economía , Infecciones por VIH/epidemiología , Accesibilidad a los Servicios de Salud , Humanos , Seguro de Servicios Farmacéuticos , Cumplimiento de la Medicación , Nigeria/epidemiología , Pandemias/economía , Neumonía Viral/economía , Neumonía Viral/epidemiología , Carga Viral/efectos de los fármacos
17.
Comput Biol Med ; 126: 104051, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33131530

RESUMEN

SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management.


Asunto(s)
Antivirales , Betacoronavirus , Infecciones por Coronavirus , Bases de Datos Genéticas , Descubrimiento de Drogas , Modelos Biológicos , Pandemias , Neumonía Viral , Antivirales/química , Antivirales/farmacocinética , Antivirales/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/genética , Neumonía Viral/metabolismo , Proteómica
18.
Am J Ther ; 27(6): e573-e583, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33136577

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 SARS- Cov2 has taken the world by surprise. Among the first promising repurposing agents proposed for treatment and prophylaxis, 2 antimalarial agents came into limelight: chloroquine and its less toxic derivative, hydroxychloroquine (HCQ). Intense research and public debates have followed. AREAS OF UNCERTAINTY: As HCQ is still used and studied, future research may bring novel evidence, modifying the state-of-the-art. Despite the lack of a single randomized control trial (RCT) with positive results, there are currently (as for the search on 30th of August 2020) more than 250 RCT registered on ClinicalTrials.gov with HCQ in COVID patients, and more than 150 of them are "still recruiting" or "not yet recruiting" patients. DATA SOURCES: Our study combines a therapeutic evaluation of RCT data with a sociological analysis of related controversies, examining scientific and public arena discourses. RESULTS: Although any hope of a positive effect was brought exclusively by some and not all of the observational studies, none of the 7 RCT published until now have found any benefit. From a sociological perspective, the HCQ controversy is a useful case study for understanding the construction of plausibility in a cultural context polarized into competing versions of reality, with different epistemologies and ideologies. CONCLUSIONS: The results of the first RCTs have been published, and they are disappointing; beneficial effects of HCQ could not be proven either for negative conversion on polymerase chain reactions of COVID patients or for postexposure prophylaxis. The question to be asked is: how many studies do we need until HCQ is abandoned? Argumentative time work, appealing to temporal properties of HCQ including its historical use, accumulation of evidence, alternative therapeutic scenarios, and sensationalist tempo for rhetorical purpose, plays a significant role in its continuing legitimation.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Betacoronavirus/aislamiento & purificación , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Política , Medición de Riesgo , Resultado del Tratamiento
19.
Clin Sci (Lond) ; 134(21): 2851-2871, 2020 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-33146371

RESUMEN

Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/enzimología , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/enzimología , Receptores Virales/metabolismo , Internalización del Virus , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Interacciones Huésped-Patógeno , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Conformación Proteica , Receptores Virales/química , Relación Estructura-Actividad
20.
Int J Med Sci ; 17(18): 3125-3145, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33173434

RESUMEN

The use of multipronged measures, including traditional Chinese medicine (TCM), has greatly increased in response to the COVID-19 pandemic, and we found the use of TCM and is positively correlated with the regional cure rate in China (R=0.77, P<10-5). We analyzed 185 commonly administered TCM recipes comprised of 210 herbs nationwide to reveal mechanistic insight. Eight out of the 10 most commonly used herbs showed anti-coronavirus potential by intersecting with COVID-19 targets. Intriguingly, 17 compounds from the 5 most commonly used herbs were revealed to have direct anti-SARS-CoV-2 potential by docking with the two core structures [CoV spike (S) glycoprotein (6SVB) and CoV 3CL hydrolase (6LU7)]. Seven reported COVID-19 drugs served as positive controls; among them, retionavir (-7.828 kcal/mol) and remdesivir (-8.738 kcal/mol) performed best with 6VSB and 6LU7, respectively. The top candidate was madreselvin B (6SVB: -8.588 kcal/mol and 6LU7: -9.017 kcal/mol), an appreciable component of Flos Lonicerae. Eighty-six compounds from 22 unlisted herbs were further identified among 2,042 natural compounds, completing our arsenal for TCM formulations. The mechanisms have been implicated as multifactorial, including activation of immunoregulation (Th2, PPAR and IL10), suppression of acute inflammatory responses (IL-6, IL-1α/ß, TNF, COX2/1, etc.), enhancement of antioxidative activity (CAT and SOD1), and modulation of apoptosis (inhibited CASP3). It is of interest to understand the biological mechanisms of TCM recipes. We then analyzed 18 representative remedies based on molecular targets associated with 14 medical conditions over the disease course, e.g., pyrexia, coughing, asthenia, lymphopenia, cytokine storm, etc. The significant level of coherence (SLC) revealed, in part, the potential uses and properties of corresponding TCMs. Thus, herbal plants coordinate to combat COVID-19 in multiple dimensions, casting a light of hope before effective vaccines are developed.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicina China Tradicional/métodos , Fitoterapia/métodos , Neumonía Viral/tratamiento farmacológico , Algoritmos , Antivirales/aislamiento & purificación , Antivirales/farmacología , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/genética , Desarrollo de Medicamentos , Medicamentos Herbarios Chinos/clasificación , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Pandemias , Fitoterapia/clasificación , Neumonía Viral/epidemiología , Neumonía Viral/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética
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