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1.
J Interferon Cytokine Res ; 40(12): 578-588, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33337933

RESUMO

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.


Assuntos
/terapia , Interferon alfa-2/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cloroquina/administração & dosagem , Comorbidade , Cuidados Críticos , Cuba/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
2.
PLoS One ; 15(12): e0244272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338063

RESUMO

OBJECTIVES: To describe the clinical characteristics of patients infected with SARS-CoV-2 at Clinique Ngaliema, a public hospital, in Kinshasa, in the Democratic Republic of Congo (DRC). METHODS: This retrospective study analyzed medical records including socio-demographics, past medical history, clinical manifestation, comorbidities, laboratory data, treatment and disease outcome of 160 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection. RESULTS: The median age of patients was 54 years (IQR: 38-64), and there was no significant gender difference (51% of male). The most common comorbidities were hypertension (55 [34%]), diabetes (31 [19%]) and obesity (13 [8%]). Fever (93 [58%]), cough (92 [57%]), fatigue (87 [54%]), shortness of breath (72 [45%]) and myalgia (33 [21%]) were the most common symptoms, upon admission. Patients were categorized into mild (92 [57%]), moderate (19 [12%]) and severe (49 [31%]). Severe patients were older and were more likely to have comorbidities, compared to mild ones. The majority of patients (92% [147 of 160]) patients received hydroxychloroquine or chloroquine phosphate. Regression model revealed that older age, lower SpO2, higher heart rate and elevated AST at admission were all risk factors associated with in-hospital death. The prevalence of COVID-19 and malaria co-infection was 0.63% and 70 (44%) of all patients received antimalarial treatment before hospitalization. CONCLUSION: Our findings indicated that the epidemiological and clinical feature of COVID-19 patients in Kinshasa are broadly similar to previous reports from other settings. Older age, lower SpO2, tachycardia, and elevated AST could help to identify patients at higher risk of death at an early stage of the illness. Plasmodium spp co-infection was not common in hospitalized COVID-19 patients.


Assuntos
/diagnóstico , /epidemiologia , Adulto , Idoso , Coagulação Sanguínea , Cloroquina/administração & dosagem , Cloroquina/análogos & derivados , Coinfecção , Comorbidade , Tosse , República Democrática do Congo/epidemiologia , Feminino , Febre , Hospitalização , Hospitais Públicos , Humanos , Hidroxicloroquina/administração & dosagem , Inflamação , Testes de Função Hepática , Malária/complicações , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Classe Social , Taquicardia/complicações
3.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32876222

RESUMO

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Assuntos
Infecções por Coronavirus/epidemiologia , Inflamação/virologia , Pneumonia Viral/epidemiologia , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Humanos , Hidroxicloroquina/administração & dosagem , Inflamação/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia
4.
J Bras Nefrol ; 42(2 suppl 1): 49-50, 2020 Aug 26.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32877501

RESUMO

Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.


Assuntos
Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Insuficiência Renal , Brasil , Humanos , Nefrologia , Pandemias , Sociedades Médicas
5.
BMB Rep ; 53(10): 545-550, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958120

RESUMO

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].


Assuntos
Azitromicina/efeitos adversos , Cardiotoxicidade/etiologia , Cloroquina/efeitos adversos , Células-Tronco Embrionárias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação , Animais , Arritmias Cardíacas/induzido quimicamente , Azitromicina/administração & dosagem , Diferenciação Celular , Cloroquina/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Humanos , Camundongos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
7.
J Interferon Cytokine Res ; 40(10): 469-471, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32881593

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.


Assuntos
Anti-Infecciosos/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Anti-Infecciosos/efeitos adversos , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Cloroquina/efeitos adversos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Resultado do Tratamento
9.
Cochrane Database Syst Rev ; 9: CD010458, 2020 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892362

RESUMO

BACKGROUND: Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver stage of the parasite, but treatment is required for 14 days. Primaquine also causes haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment. OBJECTIVES: To assess the effects of tafenoquine 300 mg (single dose) on preventing P vivax relapse. SEARCH METHODS: We searched the following up to 3 June 2020: the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; Embase; and three other databases. We also searched the WHO International Clinical Trial Registry Platform and the metaRegister of Controlled Trials for ongoing trials using "tafenoquine" and "malaria" as search terms up to 3 June 2020. SELECTION CRITERIA: Randomized controlled trials (RCTs) that gave TQ to prevent relapse in people with P vivax malaria. We planned to include trials irrespective of whether participants had been screened for G6PD enzyme deficiency. DATA COLLECTION AND ANALYSIS: All review authors independently extracted data and assessed risk of bias. As true relapse and reinfection are difficult to differentiate in people living in endemic areas, studies report "recurrences" of infection as a proxy for relapse. We carried out meta-analysis where appropriate, and gave estimates as risk ratios (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Three individually randomized RCTs met our inclusion criteria, all in endemic areas, and thus reporting recurrence. Trials compared TQ with PQ or placebo, and all participants received chloroquine (CQ) to treat the asexual infection). In all trials, pregnant and G6PD-deficient people were excluded. Tafenoquine 300 mg single dose versus no treatment for relapse prevention Two trials assessed this comparison. TQ 300 mg single dose reduces P vivax recurrences compared to no antihypnozoite treatment during a six-month follow-up, but there is moderate uncertainty around effect size (RR 0.32, 95% CI 0.12 to 0.88; 2 trials, 504 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (2 trials, 504 participants; moderate-certainty evidence). However, we are uncertain if TQ causes more serious adverse events (2 trials, 504 participants; very low-certainty evidence). Both RCTs reported a total of 23 serious adverse events in TQ groups (One RCT reported 21 events) and a majority (15 events) were a drop in haemoglobin level by > 3g/dl (or >30% reduction from baseline). Tafenoquine 300 mg single dose versus primaquine 15 mg/day for 14 days for relapse prevention Three trials assessed this comparison. There is probably little or no difference between TQ and PQ in preventing recurrences (proxy measure for relapse) up to six months of follow-up (RR 1.04, 95% CI 0.8 to 1.34; 3 trials, 747 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (3 trials, 747 participants; moderate-certainty evidence). We are uncertain if TQ can cause more serious adverse events compared to PQ (3 trials, 747 participants; very low-certainty evidence). Two trials had higher point estimates against TQ while the other showed the reverse. Most commonly reported serious adverse event in TQ group was a decline in haemoglobin level (19 out of 29 events). Some other serious adverse events, though observed in the TQ group, are unlikely to be caused by it (Hepatitis E infection, limb abscess, pneumonia, menorrhagia). AUTHORS' CONCLUSIONS: TQ 300 mg single dose prevents relapses after clinically parasitologically confirmed P vivax malaria compared to no antihypnozoite treatment, and with no difference detected in studies comparing it to PQ to date. However, the inability to differentiate a true relapse from a recurrence in the available studies may affect these estimates. The drug is untested in children and in people with G6PD deficiency. Single-dose treatment is an important practical advantage compared to using PQ for the same purpose without an overall increase in adverse events in non-pregnant, non-G6PD-deficient adults.


Assuntos
Aminoquinolinas/administração & dosagem , Antimaláricos/administração & dosagem , Malária Vivax/tratamento farmacológico , Primaquina/administração & dosagem , Prevenção Secundária , Adulto , Aminoquinolinas/efeitos adversos , Antimaláricos/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Esquema de Medicação , Deficiência de Glucosefosfato Desidrogenase/complicações , Humanos , Parasitemia/tratamento farmacológico , Placebos , Primaquina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva
10.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919428
11.
Toxicol Appl Pharmacol ; 406: 115237, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920000

RESUMO

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.


Assuntos
Betacoronavirus , Simulação por Computador , Mineração de Dados/métodos , Toxicogenética/métodos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Bases de Dados Genéticas , Quimioterapia Combinada , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
12.
PLoS Negl Trop Dis ; 14(7): e0008526, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735631

RESUMO

Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/prevenção & controle , Plasmodium vivax , Complicações Parasitárias na Gravidez/prevenção & controle , Primaquina/administração & dosagem , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Criança , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Feminino , Humanos , Malária Vivax/tratamento farmacológico , Modelos Biológicos , Gravidez , Primaquina/uso terapêutico , Recidiva , Adulto Jovem
13.
Eur J Med Res ; 25(1): 37, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854774

RESUMO

BACKGROUND: COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases. CASE PRESENTATION: Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment. CONCLUSIONS: An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Azitromicina/administração & dosagem , Betacoronavirus , Cloroquina/administração & dosagem , Infecções por Coronavirus/diagnóstico por imagem , Citocinas/metabolismo , Humanos , Inflamação , Masculino , Uso Off-Label , Pandemias , Pneumonia Viral/diagnóstico por imagem , Polônia , Tomografia Computadorizada por Raios X
14.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. Impr.) ; 46(supl.1): 20-27, ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-192623

RESUMO

ANTECEDENTES Y OBJETIVOS: En los momentos de extrema gravedad en los que nos encontramos, y ante la incertidumbre acerca de los tratamientos más eficaces en la lucha contra la enfermedad COVID-19 y con el objetivo de conocer las evidencias que pueden sostener la recomendación de utilización de cloroquina/hidroxicloroquina en el COVID 19, se realizó una revisión sistemática de estudios publicados y EC puestos en marcha con fecha hasta 28 de abril 2020. MATERIAL Y MÉTODOS: Se realizó una búsqueda sistemática en PubMed con las palabras clave COVID-19 y sus sinónimos y cloroquina/hidroxicloroquina. La selección y extracción de los datos aparecidos en dicha búsqueda fue realizada por dos investigadores de forma independiente. Los resultados se discutieron con un grupo clínico de médicos de Atención Primaria y se sintetizaron los resultados mediante tablas de GRADE. RESULTADOS: Se encontró una revisión sistemática de buena calidad que incluye artículos con elevado riesgo de sesgos. Y 8 EC puestos en marcha que arrojarán resultados más allá de mayo de 2020. CONCLUSIONES: Aunque las conclusiones de la revisión sistemática generan una baja confianza en los resultados, y las variables clínicas que muestran beneficio son variables intermedias, los efectos secundarios son asumibles y podrían ser minimizados con el uso de herramientas de riesgo de alargamiento del QT, por lo que se podría hacer una recomendación débil a favor del uso de cloroquina/hidroxicloroquina en pacientes con COVID-19 en estadio leve-moderado


BACKGROUND AND OBJECTIVES: In this moments, of extreme gravity in which we find ourselves, and in the uncertainty face about the most effective treatment against COVID-19 disease and with the aim of find the evidence that support the chloroquine/hydroxychloroquine use recommendation to treat COVID-19 disease, a systematic review of published studies and RCT studies publishes until April 28, 2020 was carried out. MATERIAL AND METHODS: A systematic search was carried out in PubMed with the keywords COVID-19 and their synonyms and hydroxychloroquine/chloroquine. The data selection and extraction was elaborated by two researchers, independently. The results were discussed with a Primary Care physicians clinical group and the results were synthesized using GRADE methodology. RESULTS: A good quality systematic review was found that includes articles with a high risk of bias. And 8 EC launched that will produce results beyond May 2020. CONCLUSIONS: Although the conclusions of the systematic review generate a low confidence in the results, and the clinical variables that show benefit are intermediate variables, the side effects are acceptable and could be minimized with the use of QT lengthening risk tools, so it is could make a weak recommendation in favor of the use of chloroquine/hydroxychloroquine in patients with mild-moderate stage COVID-19


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vírus da SARS/patogenicidade , Hidroxicloroquina/administração & dosagem , Cloroquina/administração & dosagem , Antimaláricos/administração & dosagem , Pandemias , Atenção Primária à Saúde/organização & administração
16.
J Interv Card Electrophysiol ; 59(2): 337-345, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32654098

RESUMO

PURPOSE: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients. METHODS: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias. RESULTS: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations. CONCLUSIONS: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.


Assuntos
Antimaláricos/efeitos adversos , Azitromicina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/métodos , Síndrome do QT Longo/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/administração & dosagem , Azitromicina/administração & dosagem , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Incidência , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Medição de Risco , Distribuição por Sexo , População Urbana
17.
Therapie ; 75(4): 335-342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32665090

RESUMO

Since December 2019, the COVID-19 pandemic has become a major public health problem. To date, there is no evidence of a higher incidence of COVID in patients with autoimmune rheumatic diseases and we support the approach of maintaining chronic rheumatological treatments. However, once infected there is a small but significant increased risk of mortality. Among the different treatments, NSAIDs are associated with higher rates of complications, but data for other drugs are conflicting or incomplete. The use of certain drugs for autoimmune inflammatory rheumatisms appears to be a potentially interesting options for the treatment. The rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines (Il1, IL6, TNFα) in severe forms of the disease. Notably, patients on chloroquine or hydroxychloroquine as a treatment for their autoimmune rheumatic disease are not protected from COVID-19.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/epidemiologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Antirreumáticos/administração & dosagem , Doenças Autoimunes/tratamento farmacológico , Cloroquina/administração & dosagem , Infecções por Coronavirus/mortalidade , Humanos , Hidroxicloroquina/administração & dosagem , Incidência , Pandemias , Pneumonia Viral/mortalidade , Doenças Reumáticas/tratamento farmacológico
18.
Elife ; 92020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32639233

RESUMO

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.


Assuntos
Cloroquina/envenenamento , Overdose de Drogas/mortalidade , Tentativa de Suicídio , Suicídio , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/envenenamento , Antimaláricos/uso terapêutico , Biotransformação , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Cloroquina/análogos & derivados , Cloroquina/sangue , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Eletrocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/mortalidade , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/envenenamento , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Malária/tratamento farmacológico , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Medição de Risco
19.
Int J Antimicrob Agents ; 56(3): 106101, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32687949

RESUMO

The coronavirus infection (COVID-19) has turned into a global catastrophe and there is an intense search for effective drug therapy. Of all the potential therapies, chloroquine and hydroxychloroquine have been the focus of tremendous public attention. Both drugs have been used in the treatment and prophylaxis of malaria. Long-term use of hydroxychloroquine is the cornerstone in the treatment of several auto-immune disorders. There is convincing evidence that hydroxychloroquine has strong in vitro antiviral activity against SARS-CoV-2. A few small uncontrolled trials and several anecdotal reports have shown conflicting results of such drug therapy in COVID-19. However, the results of preliminary large-scale randomized controlled trials have failed to show any survival benefit of such drug therapy in COVID-19. Despite the lack of such evidence, hydroxychloroquine has been used as a desperate attempt for prophylaxis and treatment of COVID-19. The drug has wide-ranging drug interactions and potential cardiotoxicity. Indiscriminate unsupervised use can expose the public to serious adverse drug effects.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hidroxicloroquina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Cloroquina/efeitos adversos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Esquema de Medicação , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Análise de Sobrevida , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
20.
J Nanosci Nanotechnol ; 20(12): 7311-7323, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711596

RESUMO

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.


Assuntos
Antivirais/química , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/química , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Adenina/administração & dosagem , Adenina/análogos & derivados , Adenina/química , Adenina/farmacologia , Adenosina/análogos & derivados , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Alanina/administração & dosagem , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Amidas/administração & dosagem , Amidas/química , Amidas/farmacologia , Antivirais/administração & dosagem , Sítios de Ligação , Cloroquina/administração & dosagem , Cloroquina/química , Cloroquina/farmacologia , Interações Medicamentosas , Humanos , Ligação de Hidrogênio , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Hidroxicloroquina/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Nanotecnologia , Pandemias , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem , Pirazinas/química , Pirazinas/farmacologia , Pirrolidinas/administração & dosagem , Pirrolidinas/química , Pirrolidinas/farmacologia , Ribavirina/administração & dosagem , Ribavirina/química , Ribavirina/farmacologia , Eletricidade Estática
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