Uso da cloroquina e da hidroxicloroquina no tratamento da COVID-19: riscos e benefícios segundo uma revisão integrativa / Use of chlorochine and hydroxychlorocchine in the treatment of COVID-19 risks and benefits according to an integrative review

Introdução: Responsável pela doença COVID-19, o novo corona-vírus, denominado SARS-CoV-2, foi descoberto na China. A sua rápida propagação causou espanto e preocupação e ocasionou uma das maiores pandemias já registradas na história. Para o tratamento da infecção, alguns profissionais sugerem o uso da Cloroquina e da Hidroxicloroquina, medicamentos utilizados para o tratamento de diversas doenças há mais de 70 anos. Entretanto, a efetividade des-ses medicamentos no controle da COVID-19 ainda não foi confir-mada. Objetivos: Identificar na literatura científica os riscos e bene-fícios da Cloroquina e da Hidroxicloroquina utilizados como terapia medicamentosa para pacientes com COVID-19. Método: Revisão integrativa da literatura, utilizando três bancos de dados on-line (LILACS, SCIELO e PUBMED) a fim de descrever os efeitos da Cloroquina e da Hidroxicloroquina quando usadas no tratamento da doença, permitindo a avaliação crítica de determinado conhecimen-to sobre o assunto e reunindo múltiplos estudos e suas principais considerações. Resultados: Foram analisados dez estudos científi-cos acerca da temática, focando na relação riscos e benefícios que os medicamentos Cloroquina e Hidroxicloroquina, associados ou não a outros medicamentos, possam apresentar no combate à infec-ção. Os dados in vitro apresentaram resultados promissores quan-to ao uso dos medicamentos, porém não demonstraram eficácia no combate à COVID-19 quando utilizados em pacientes. Considera-ções finais: Conclui-se que a utilização de Cloroquina e Hidroxi-cloroquina no tratamento da COVID-19 mostra-se ineficaz e com riscos para quem faz uso. Nota-se uma concordância com relação à necessidade de cautela no momento, com destaque para os riscos cardíacos para o usuário.

Introduction: Responsible for the disease COVID-19, the new coronavirus, called SARS-CoV-2, was discovered in China. Its rapid spread caused astonishment and concern in the population, and it ended up causing one of the largest pandemics ever recorded in history. Some professionals suggest using Chloroquine and Hydroxychloroquine, medicines that have been used to fight various diseases for more than 70 years, to treat this infection. Their effectiveness in controlling COVID-19 has not been confirmed, though. Objectives: This study aims to collect information in the scientific literature on the risks and benefits of the drugs Chloroquine and Hydroxychloroquine used as drug therapy for patients affected by the disease. Method: An integrative literature review was carried out, on three online databases (LILACS, SCIELO, and PUBMED) to describe the effects of Chloroquine and Hydroxychloroquine when used in the treatment of the disease, allowing the critical evaluation of certain knowledge on the subject, and gathering multiple studies and their main outcomes. Results: Ten scientific studies on the theme were analyzed, focusing on the relationship between risks and benefits that the medicines Chloroquine and Hydroxychloroquine, associated or not with other medicines may present in the fight against the infection. In vitro data showed promising results regarding the use of the drugs, but the medicines did not demonstrate efficiency in combating COVID-19 when used in patients. Final considerations: The use of Chloroquine and Hydroxychloroquine in the treatment of COVID-19 proves to be ineffective and it brings risks for those who use them. There is an agreement regarding the need for caution now, emphasizing heart risk to the user.

Primum non nocere - Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.(AU)

La evidencia en tiempos de coronavirus (COVID-19) / Evidence in times of coronavirus (COVID-19)

La pandemia de COVID-19 está generando información epidemiológica y clínica en una escala sin precedentes para una enfermedad de reciente aparición. Aunque ya se han iniciado numerosos ensayos clínicos de fármacos antiguos y nuevos como potenciales antivirales específicos, la mayor parte de la información publicada hasta ahora carece de los controles básicos para la evaluación de la eficacia de un medicamento. Los medios de comunicación amplifican estos resultados preliminares y suman presión a los médicos asistenciales y a los decisores de políticas públicas. Este artículo revisa las pruebas disponibles sobre los cuatro tratamientos antivirales específicos más prometedores: hidroxicloroquina, lopinavir/ritonavir, remdesvir e interferones alfa y beta. Se comprueba en todos ellos que no hay demostración suficiente de eficacia como para recomendar su uso fuera de una investigación experimental adecuadamente controlada. En el uso individual de un medicamento no hay forma de saber si está beneficiando o perjudicando al paciente. Es erróneo asumir que la eventual curación se debe al fármaco y un mal desenlace debe atribuirse a la enfermedad. Sólo la comparación entre grupos de pacientes asignados al tratamiento experimental o a un control adecuado permite conocer la eficacia y seguridad de las intervenciones. El desafío es conciliar la urgencia de actuar con la generación de nuevos conocimientos.Aunque no resulta sencillo organizar ensayos clínicos en este contexto, las instituciones pueden sumarse a los proyectos en marcha a nivel nacional e internacional. El uso de estos fármacos debe considerarse experimental, por lo que es necesario obtener el consentimiento informado del paciente. (AU)

The COVID-19 pandemic is generating epidemiological and clinical information on an unprecedented scale for a newly emerging disease. Although numerous clinical trials of old and new drugs as potential specific antivirals have already been started, most of the information published so far lacks basic controls for evaluating drug efficacy. The media amplify these preliminary results and add pressure to doctors and policymakers. This article reviews the available evidence for the four most promising specific antiviral treatments: hydroxychloroquine, lopinavir / ritonavir, remdesvir, and alpha and beta interferons. The findings show that none of them has sufficient demonstration of efficacy to recommend its use outside ofthe adequately controlled experimental study. In the individual use of a drug there is no way of knowing if it is benefiting orharming the patient. It is wrong to assume that the eventual cure is due to the drug and a poor outcome must be attributed to the disease. Only the comparison between groups of patients assigned to the experimental treatment or to an adequate control can establish the efficacy and safety of the interventions. The challenge is to reconcile the urgency to act with the generation of new knowledge. Although it is not easy to organize clinical trials in this context, the institutions can join theongoing projects at the national and international levels. The use of these drugs should be considered experimental, so it is necessary to obtain the informed consent of the patient. (AU)

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients

OBJECTIVES: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients. METHODS: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients. RESULTS: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication. .

La hidroxicloroquina en el tratamiento del lupus eritematoso sistémico / Hydroxychloroquine in the treatment of systemic lupus erythematosus

The positive effects of hydroxychloroquine in treating systemic lupus erythematosus is well known. Hydroxychloroquine is a well tolerated and safe drug even during pregnancy and breast feeding, and it has a low cost. Retinopathy is the most serious side-effect associated with its use since irreversible blindness can occur; therefore, an appropriate monitoring of the eye by an ophthalmologist becomes essential. The remarkable effectiveness of hydroxychloroquine to control disease activity has been demonstrated; and there is also evidence suggesting that this drug contributes to prevent damage accrual and to improve survival in lupus patients. Besides the immunomodulating and immunosuppressant properties of hydroxychloroquine, it also has beneficial effects on lipid and glucose metabolism as well as antithrombotic effects that could contribute to prevent arteriosclerosis in these patients

La utilidad de la hidroxicloroquina en el tratamiento del lupus eritematoso sistémico está ampliamente demostrada. Es un fármaco seguro (incluso durante el embarazo y la lactancia), bien tolerado y económico. La retinopatía asociada a su uso es el único efecto adverso realmente peligroso por cuanto puede provocar ceguera irreversible, que puede evitarse mediante un adecuado control oftalmológico. Existen suficientes datos que respaldan el notable efecto que tiene la hidroxicloroquina sobre el control de la actividad de la enfermedad. También hay hallazgos que sugieren que disminuye el daño acumulado en los pacientes lúpicos y podría aumentar su supervivencia. Las propiedades de la hidroxicloroquina parecen ir más allá de su efecto inmumodulador e inmunosupresor. Así, tiene efectos beneficiosos sobre el metabolismo lipídico y glucémico y efectos antitrombóticos que podrían contribuir a prevenir la aterosclerosis