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1.
Front Immunol ; 12: 580147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936026

RESUMO

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies' seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12-22.84%) and 36.36% (95% CI 12.36-68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.


Assuntos
Anticorpos Antivirais/imunologia , Antimaláricos/efeitos adversos , Imunoglobulina G/imunologia , Adolescente , Adulto , Idoso , /tratamento farmacológico , Cefalosporinas/efeitos adversos , China , Cloroquina/efeitos adversos , Convalescença , Feminino , Febre/complicações , Febre/virologia , Humanos , Hidroxicloroquina/efeitos adversos , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Neoplasias/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Soroconversão , Testes Sorológicos
2.
Ann Palliat Med ; 10(3): 3307-3312, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849115

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19. METHODS: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups. RESULTS: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment. CONCLUSIONS: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.


Assuntos
Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Indóis/uso terapêutico , China , Cloroquina/efeitos adversos , Humanos , Tempo de Internação , Estudos Retrospectivos
3.
Glob Heart ; 16(1): 18, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33833942

RESUMO

The current pandemic of SARS-COV 2 infection (Covid-19) is challenging health systems and communities worldwide. At the individual level, the main biological system involved in Covid-19 is the respiratory system. Respiratory complications range from mild flu-like illness symptoms to a fatal respiratory distress syndrome or a severe and fulminant pneumonia. Critically, the presence of a pre-existing cardiovascular disease or its risk factors, such as hypertension or type II diabetes mellitus, increases the chance of having severe complications (including death) if infected by the virus. In addition, the infection can worsen an existing cardiovascular disease or precipitate new ones. This paper presents a contemporary review of cardiovascular complications of Covid-19. It also specifically examines the impact of the disease on those already vulnerable and on the poorly resourced health systems of Africa as well as the potential broader consequences on the socio-economic health of this region.


Assuntos
/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/fisiopatologia , África , Antimaláricos/efeitos adversos , Arritmias Cardíacas/economia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , /economia , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/etiologia , Cloroquina/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Atenção à Saúde/economia , Recessão Econômica , Produto Interno Bruto , Recursos em Saúde/economia , Recursos em Saúde/provisão & distribuição , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hidroxicloroquina/efeitos adversos , Inflamação , Isquemia Miocárdica/economia , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/fisiopatologia , Miocardite/economia , Miocardite/etiologia , Miocardite/fisiopatologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/fisiopatologia , Fatores Socioeconômicos , Cardiomiopatia de Takotsubo/economia , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/fisiopatologia
4.
Nat Commun ; 12(1): 2349, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859192

RESUMO

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.


Assuntos
/tratamento farmacológico , Cloroquina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Complicações Infecciosas na Gravidez/mortalidade , Adulto , /virologia , Criança , Cloroquina/administração & dosagem , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Comorbidade , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Cooperação Internacional , Razão de Chances , Participação do Paciente/estatística & dados numéricos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
5.
Medicine (Baltimore) ; 100(16): e25532, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879694

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. OBJECTIVE: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. METHODS: Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events. RESULTS: A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79-1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98-1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01-1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63-0.88, P < .05) of COVID-19 medicine is lower than control group. CONCLUSION: The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.


Assuntos
Antivirais/efeitos adversos , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/mortalidade , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , SARS-CoV-2 , Resultado do Tratamento
6.
Eur J Intern Med ; 88: 63-72, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33832827

RESUMO

OBJECTIVE: To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users. METHODS: We systematically reviewed randomized controlled trials (RCTs), using MEDLINE (2010-2020) and EMBASE (2010-2020) databases, reporting AE in chloroquine or hydroxychloroquine users during treatment for lupus, rheumatoid arthritis, malaria and COVID-19. The protocol for this systematic review is registered at the PROSPERO database (CRD42020197938). The quality of the included studies was assessed using the Cochrane risk-of-Bias tool and relevant data were extracted though a customized data collection form, independently, by two authors. The IRR of AE was estimated using a random-effect model meta-analysis and heterogeneity was evaluated by T2 and I2. Subgroup analysis was performed, and publication bias was assessed by funnel-plot. RESULTS: Forty-six RCTs met our eligibility criteria and were included in our analysis (23132 patients). There was not a single death attributed to chloroquine or hydroxychloroquine use in the included RCTs. The IRR of general AE during antimalarial use was 1.15 [CI 95% 1.01-1.31]. COVID-19 patients treated with either antimalarial presented an 83% and 165% higher risk of developing general and gastrointestinal AE, respectively, in comparison with controls. The use of antimalarial increased the risk of developing dermatological AE by 92% in malarial studies and reduced by 65% in lupus studies. We did not find a significatively higher risk of cardiovascular nor ophthalmological AE in antimalarial users. CONCLUSIONS: Our data reinforces that chloroquine and hydroxychloroquine have a good safety profile though caution is advised when using higher than usual doses in hospitalized COVID-19 patients.


Assuntos
Hidroxicloroquina , /tratamento farmacológico , Cloroquina/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos
7.
Scand J Trauma Resusc Emerg Med ; 29(1): 48, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722251

RESUMO

BACKGROUND: Chloroquine use has increased worldwide recently in the setting of experimental treatment for the novel coronavirus disease (Covid-19). Nevertheless, in case of chloroquine intoxication, it can be life threatening, with cardiac arrest, due to its cardiac toxicity. CASE PRESENTATION: This case study reports on a 14-years-old girl who presented in cardiac arrest after an uncommon suicide attempt by ingesting 3 g of chloroquine. After 66 min of cardio-pulmonary resuscitation (CPR), extracorporeal cardiopulmonary resuscitation (ECPR) was initiated, allowing cardiac function to recover. CONCLUSIONS: Chloroquine intoxication is a rare but serious condition due to its cardiac toxicity. Use of ECPR in this case of transient toxicity allowed a favorable evolution with little neurological impairment.


Assuntos
/tratamento farmacológico , Reanimação Cardiopulmonar/métodos , Cloroquina/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Adolescente , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Feminino , Parada Cardíaca/induzido quimicamente , Humanos , Pandemias , Índice de Gravidade de Doença
8.
J Infect Chemother ; 27(6): 882-889, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33678548

RESUMO

INTRODUCTION: Hydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model. RESULTS: Pooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00-1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31-1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55-4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58-1.88). CONCLUSIONS: HCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.


Assuntos
/tratamento farmacológico , Cloroquina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Resultado do Tratamento
9.
Euro Surveill ; 26(9)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33663646

RESUMO

BackgroundSeveral clinical trials have assessed the protective potential of chloroquine and hydroxychloroquine. Chronic exposure to such drugs might lower the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or severe coronavirus disease (COVID-19).AimTo assess COVID-19 incidence and risk of hospitalisation in a cohort of patients chronically taking chloroquine/hydroxychloroquine.MethodsWe used linked health administration databases to follow a cohort of patients with chronic prescription of hydroxychloroquine/chloroquine and a control cohort matched by age, sex and primary care service area, between 1 January and 30 April 2020. COVID-19 cases were identified using International Classification of Diseases 10 codes.ResultsWe analysed a cohort of 6,746 patients (80% female) with active prescriptions for hydroxychloroquine/chloroquine, and 13,492 controls. During follow-up, there were 97 (1.4%) COVID-19 cases in the exposed cohort and 183 (1.4%) among controls. The incidence rate was very similar between the two groups (12.05 vs 11.35 cases/100,000 person-days). The exposed cohort was not at lower risk of infection compared with controls (hazard ratio (HR): 1.08; 95% confidence interval (CI): 0.83-1.44; p = 0.50). Forty cases (0.6%) were admitted to hospital in the exposed cohort and 50 (0.4%) in the control cohort, suggesting a higher hospitalisation rate in the former, though differences were not confirmed after adjustment (HR: 1·46; 95% CI: 0.91-2.34; p = 0.10).ConclusionsPatients chronically exposed to chloroquine/hydroxychloroquine did not differ in risk of COVID-19 nor hospitalisation, compared with controls. As controls were mainly female, findings might not be generalisable to a male population.


Assuntos
Antivirais/uso terapêutico , /epidemiologia , Cloroquina/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Incidência , Masculino , Estudos Prospectivos , Espanha/epidemiologia
10.
Biomed Res Int ; 2021: 8821318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732744

RESUMO

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.


Assuntos
/tratamento farmacológico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
11.
Food Chem Toxicol ; 151: 112106, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33722600

RESUMO

The review summarizes chloroquine (CQ) and its safer derivative hydroxychloroquine (HCQ) and its utility in Covid-19. Recently this well-established drug made its way back to the headlines during the SARS-CoV-2 pandemic. This led to an upsurge in the scientific arena with multiple research and review articles along with expert opinions and commentaries. The HCQ has received mixed judgements so far about its efficacy to be used in Covid-19 patients in a limited trial conducted all across the Globe. The purpose of our article is to put forth the history, pharmacodynamics, and pharmacokinetics, along with the existing studies favouring and disapproving the role of HCQ in the treatment of Covid-19. We grouped HCQ use at three stages, this includes HCQ for i. prophylactic use by asymptomatic health workers or peoples at higher risk; ii. patients having mild symptoms; iii. patients with extreme symptoms. The review critically discusses the underlying plausible reasons and mechanisms exploring HCQ in prophylactic management or treatment of SARS-CoV-2. Furthermore, we have critically analysed the reported pharmacokinetic parameters and compiled the proponent, opponent, or neutral opinions on the use of HCQ in Covid-19. Authors discretion is to conduct more studies considering the optimal dosing regimen and pharmacokinetics assessment.


Assuntos
Antivirais/uso terapêutico , Hidroxicloroquina/uso terapêutico , Animais , Antivirais/efeitos adversos , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/efeitos adversos , Pandemias
12.
Pharmacoepidemiol Drug Saf ; 30(6): 694-706, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33772933

RESUMO

PURPOSE: Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early pandemic period. It is well-known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID-19 patients treated with these drugs. METHODS: We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500 ms, peak QTc change ≥60 ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta-analyses were conducted using a random-effects model. RESULTS: Forty-seven studies (three case series, 35 cohorts, and nine randomized controlled trials [RCTs]) involving 13 087 patients were included. The pooled prevalence of peak QTc ≥500 ms was 9% (95% confidence interval [95%CI], 3%-18%) and 8% (95%CI, 3%-14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56-4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16-9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation. CONCLUSIONS: COVID-19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low, probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.


Assuntos
Azitromicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Azitromicina/administração & dosagem , /epidemiologia , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Síndrome do QT Longo/diagnóstico , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Estudos Observacionais como Assunto/métodos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
13.
Cochrane Database Syst Rev ; 3: CD007478, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687069

RESUMO

BACKGROUND: Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits. OBJECTIVES: To assess the effects of interventions for cutaneous disease in SLE. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence. MAIN RESULTS: Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate. AUTHORS' CONCLUSIONS: Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/terapia , Dermatopatias/terapia , Idade de Início , Azatioprina/uso terapêutico , Viés , Fatores Biológicos/uso terapêutico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Técnicas Cosméticas , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Exantema , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Cutâneo/classificação , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/terapia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Masculino , Medicina Tradicional Chinesa , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Dermatopatias/etiologia , Exacerbação dos Sintomas
14.
Ann Agric Environ Med ; 28(1): 122-126, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33775077

RESUMO

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic causes vital concerns due to the lack of proved, effective, and safe therapy. Chloroquine and hydroxychloroquine seem to be useful, but recently serious concerns regarding their adverse events have risen. The aim of the study was to broaden the general perspective of chloroquine and hydroxychloroquine use in COVID-19 treatment, based on an analysis of their current safety profile among patients with rheumatic diseases. MATERIAL AND METHODS: The study was based on a group of 152 patients with rheumatic diseases, aged 20-78 years, treated either with chloroquine or hydroxychloroquine. Analyzed data included age, gender, comorbidities, type of drug, dosage, treatment duration, and reported adverse events. Cases of drug withdrawal related to adverse events were also recorded. RESULTS: The dosage was consistent in both groups: 250 mg of chloroquine or 200 mg of hydroxychloroquine daily. 77.6% of patients did not experience any adverse reactions to the treatment. Hydroxychloroquine showed better safety profile, with 10.9% of patients reporting side-ffects, compared to 28.9% in patients treated with chloroquine. The overall incidence of ophthalmic complications was 6.6%. For both drugs, no statistically significant correlation between adverse events and age, chronic heart or liver disease, or hypertension was found. CONCLUSIONS: Chloroquine and hydroxychloroquine at lower doses, as used in rheumatic diseases, prove to be relatively safe. Data from the literature show that high dosage as recommended in COVID-19 treatment may pose a risk of toxicity and require precise management, but prophylactic, long-term use of lower, safe doses might be a promising solution.


Assuntos
Antirreumáticos/efeitos adversos , Cloroquina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Olho/efeitos dos fármacos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade
15.
Cochrane Database Syst Rev ; 2: CD013587, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33624299

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. OBJECTIVES: To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID-19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS-CoV-2 exposure; 3) preventing infection in people exposed to SARS-CoV-2. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled-trials.com), and the COVID-19-specific resources www.covid-nma.com and covid-19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID-19, people at risk of COVID-19 exposure, and people exposed to COVID-19. Adverse events (any, serious, and QT-interval prolongation on electrocardiogram) were also extracted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane 'Risk of bias' tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta-analysis using a random-effects model for outcomes where pooling of effect estimates was appropriate. MAIN RESULTS: 1. Treatment of COVID-19 disease We included 12 trials involving 8569 participants, all of whom were adults. Studies were from China (4); Brazil, Egypt, Iran, Spain, Taiwan, the UK, and North America (each 1 study); and a global study in 30 countries (1 study). Nine were in hospitalized patients, and three from ambulatory care. Disease severity, prevalence of comorbidities, and use of co-interventions varied substantially between trials. We found potential risks of bias across all domains for several trials. Nine trials compared HCQ with standard care (7779 participants), and one compared HCQ with placebo (491 participants); dosing schedules varied. HCQ makes little or no difference to death due to any cause (RR 1.09, 95% CI 0.99 to 1.19; 8208 participants; 9 trials; high-certainty evidence). A sensitivity analysis using modified intention-to-treat results from three trials did not influence the pooled effect estimate.  HCQ may make little or no difference to the proportion of people having negative PCR for SARS-CoV-2 on respiratory samples at day 14 from enrolment (RR 1.00, 95% CI 0.91 to 1.10; 213 participants; 3 trials; low-certainty evidence). HCQ probably results in little to no difference in progression to mechanical ventilation (RR 1.11, 95% CI 0.91 to 1.37; 4521 participants; 3 trials; moderate-certainty evidence). HCQ probably results in an almost three-fold increased risk of adverse events (RR 2.90, 95% CI 1.49 to 5.64; 1394 participants; 6 trials; moderate-certainty evidence), but may make little or no difference to the risk of serious adverse events (RR 0.82, 95% CI 0.37 to 1.79; 1004 participants; 6 trials; low-certainty evidence). We are very uncertain about the effect of HCQ on time to clinical improvement or risk of prolongation of QT-interval on electrocardiogram (very low-certainty evidence). One trial (22 participants) randomized patients to CQ versus lopinavir/ritonavir, a drug with unknown efficacy against SARS-CoV-2, and did not report any difference for clinical recovery or adverse events. One trial compared HCQ combined with azithromycin against standard care (444 participants). This trial did not detect a difference in death, requirement for mechanical ventilation, length of hospital admission, or serious adverse events. A higher risk of adverse events was reported in the HCQ-and-azithromycin arm; this included QT-interval prolongation, when measured. One trial compared HCQ with febuxostat, another drug with unknown efficacy against SARS-CoV-2 (60 participants). There was no difference detected in risk of hospitalization or change in computed tomography (CT) scan appearance of the lungs; no deaths were reported. 2. Preventing COVID-19 disease in people at risk of exposure to SARS-CoV-2 Ongoing trials are yet to report results for this objective. 3. Preventing COVID-19 disease in people who have been exposed to SARS-CoV-2 One trial (821 participants) compared HCQ with placebo as a prophylactic agent in the USA (around 90% of participants) and Canada. Asymptomatic adults (66% healthcare workers; mean age 40 years; 73% without comorbidity) with a history of exposure to people with confirmed COVID-19 were recruited. We are very uncertain about the effect of HCQ on the primary outcomes, for which few events were reported: 20/821 (2.4%) developed confirmed COVID-19 at 14 days from enrolment, and 2/821 (0.2%) were hospitalized due to COVID-19 (very low-certainty evidence). HCQ probably increases the risk of adverse events compared with placebo (RR 2.39, 95% CI 1.83 to 3.11; 700 participants; 1 trial; moderate-certainty evidence). HCQ may result in little or no difference in serious adverse events (no RR: no participants experienced serious adverse events; low-certainty evidence). One cluster-randomized trial (2525 participants) compared HCQ with standard care for the prevention of COVID-19 in people with a history of exposure to SARS-CoV-2 in Spain. Most participants were working or residing in nursing homes; mean age was 49 years. There was no difference in the risk of symptomatic confirmed COVID-19 or production of antibodies to SARS-CoV-2 between the two study arms. AUTHORS' CONCLUSIONS: HCQ for people infected with COVID-19 has little or no effect on the risk of death and probably no effect on progression to mechanical ventilation. Adverse events are tripled compared to placebo, but very few serious adverse events were found. No further trials of hydroxychloroquine or chloroquine for treatment should be carried out. These results make it less likely that the drug is effective in protecting people from infection, although this is not excluded entirely. It is probably sensible to complete trials examining prevention of infection, and ensure these are carried out to a high standard to provide unambiguous results.


Assuntos
Antimaláricos/uso terapêutico , /prevenção & controle , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Adulto , Idoso , Antimaláricos/efeitos adversos , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Viés , /mortalidade , Causas de Morte , Cloroquina/efeitos adversos , Humanos , Hidroxicloroquina/efeitos adversos , Pessoa de Meia-Idade , Pandemias , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos , Padrão de Cuidado , Resultado do Tratamento
17.
Pathog Glob Health ; 115(3): 139-150, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33573530

RESUMO

COVID-19 has quickly become a public health problem worldwide, and treatment for this new disease is needed. Hydroxychloroquine is an antimalarial that in vitro studies have shown action against SARS-CoV-2, which is why it has been the target of clinical studies with conflicting results. Therefore, the aim of this systematic review was to assess the association of hydroxychloroquine use with the virological cure, clinical recovery, mortality, and development of adverse effects in patients with COVID-19. PubMed, Cochrane Library, and Lilacs were searched until 7 January 2021, for randomized clinical trials with COVID-19 patients treated with hydroxychloroquine or chloroquine. Of the 130 studies found, 12 met the inclusion criteria. Compared to the patient's control group, the risk ratio (RR) for the virological cure and clinical recovery with hydroxychloroquine or chloroquine use was 1.04 (95%CI 0.91-1.17) and 1.03 (95%CI 0.92-1.13), respectively. Hydroxychloroquine (with or without azithromycin) was also not associated with mortality (RR = 1.09, 95%CI 0.98-1.20). Treatment with hydroxychloroquine was associated with any adverse effects (RR = 1.50, 95%CI 1.18-1.81). Hydroxychloroquine or chloroquine use did not have a significant effect on virological cure, the time of clinical recovery, and improvement in survival in COVID-19 patients. However, patients who used hydroxychloroquine showed an increase in adverse effects.


Assuntos
/tratamento farmacológico , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Antivirais/uso terapêutico , /virologia , Cloroquina/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , /genética , Resultado do Tratamento
18.
Toxicol Sci ; 180(2): 356-368, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33483756

RESUMO

Substantial efforts have been recently committed to develop coronavirus disease-2019 (COVID-19) medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. Although these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the proarrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low proarrhythmia risk, whereas Chloroquine and Azithromycin were associated with high risk. Hydroxychloroquine proarrhythmia risk changed to high with low level of K+, whereas high level of Mg2+ protected against proarrhythmic effect of high Hydroxychloroquine concentrations. Moreover, therapeutic concentration of Hydroxychloroquine caused no enhancement of elevated temperature-induced proarrhythmia. Polytherapy of Hydroxychloroquine plus Azithromycin and sequential application of these drugs were also found to influence proarrhythmia risk categorization. Hydroxychloroquine proarrhythmia risk changed to high when combined with Azithromycin at therapeutic concentration. However, Hydroxychloroquine at therapeutic concentration impacted the cardiac safety profile of Azithromycin and its proarrhythmia risk only at concentrations above therapeutic level. We also report that Hydroxychloroquine and Chloroquine, but not Azithromycin, decreased contractility while exhibiting multi-ion channel block features, and Hydroxychloroquine's contractility effect was abolished by Azithromycin. Thus, this study has the potential to inform clinical studies evaluating repurposed therapies, including those in the COVID-19 context. Additionally, it demonstrates the translational value of the human cardiomyocyte contractility-based model as a key early discovery path to inform decisions on novel therapies for COVID-19, malaria, and inflammatory diseases.


Assuntos
Antivirais/efeitos adversos , Cardiotoxicidade , Cloroquina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Medição de Risco , Estados Unidos
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