Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome.
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ABSTRACT:
SUBMITTER: Okour M
PROVIDER: S-EPMC7220612 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome.
Okour Malek M Al-Kofahi Mahmoud M Austin Daren D
Journal of pharmacokinetics and pharmacodynamics 20200513 3
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Project description:One of the most impact issues in recent years refers to the COVID-19 pandemic, the consequences of which thousands of deaths recorded worldwide, are still inferior understood. Its impacts on the environment and aquatic biota constitute a fertile field of investigation. Thus, to predict the impact of the indiscriminate use of azithromycin (AZT) and hydroxychloroquine (HCQ) in this pandemic context, we aim to assess their toxicological risks when isolated or in combination, using zebrafish (Danio rerio) as a model system. In summary, we observed that 72 h of exposure to AZT and HCQ (alone or in binary combination, both at 2.5 μg/L) induced the reduction of total protein levels, accompanied by increased levels of thiobarbituric acid reactive substances, hydrogen peroxide, reactive oxygen species and nitrite, suggesting a REDOX imbalance and possible oxidative stress. Molecular docking analysis further supported this data by demonstrating a strong affinity of AZT and HCQ with their potential antioxidant targets (catalase and superoxide dismutase). In the protein-protein interaction network analysis, AZT showed a putative interaction with different cytochrome P450 molecules, while HCQ demonstrated interaction with caspase-3. The functional enrichment analysis also demonstrated diverse biological processes and molecular mechanisms related to the maintenance of REDOX homeostasis. Moreover, we also demonstrated an increase in the AChE activity followed by a reduction in the neuromasts of the head when zebrafish were exposed to the mixture AZT + HCQ. These data suggest a neurotoxic effect of the drugs. Altogether, our study demonstrated that short exposure to AZT, HCQ or their mixture induced physiological alterations in adult zebrafish. These effects can compromise the health of these animals, suggesting that the increase of AZT and HCQ due to COVID-19 pandemic can negatively impact freshwater ecosystems.
| S-EPMC8164503 | biostudies-literature
Project description:Alarming situation has been caused due to the emergence of COVID-19 infection around the world. There is an urgency of developing a therapeutic strategy in order to control the spread of COVID-19. Towards that initiative, potential drugs like hydroxychloroquine, ivermectin and azithromycin have been tested by diverse group of researchers worldwide for their potential against novel coronavirus. The present report presents together the comprehensive knowledge derived from the major researches about the above drugs altogether in context of the current health emergency around the world. Hydroxychloroquine and ivermectin were known to act by creating the acidic environment and inhibiting the importin (IMPα/β1) mediated viral import. Azithromycin was found to act similar to the hydroxychloroquine as an acidotropic lipophilic weak base. All the three categories of drugs seemed to potentially act against novel coronavirus infection. However, their efficacies need to be studied in detail individually and in combination in-vivo in order to combat COVID-19 infection.
| S-EPMC7175902 | biostudies-literature
Project description:BackgroundHydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.MethodsWe conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.ResultsA total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.ConclusionsAmong patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).
| S-EPMC7397242 | biostudies-literature
Project description:ObjectivesThis study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM).BackgroundHCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population.MethodsA retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality.ResultsAmong 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed.ConclusionsAn increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.
| S-EPMC7406234 | biostudies-literature
Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread use of hydroxychloroquine and azithromycin despite the lack of conclusive evidence for their safety and efficacy. We evaluated the association between treatment with hydroxychloroquine and/or azithromycin and hospital mortality as the primary outcome. We compared the hospital mortality of patients treated with hydroxychloroquine alone, azithromycin alone, or their combination to the mortality of patients who received neither drug. A logistic multivariate model with overlap weight propensity score was used for estimation of odds ratios (ORs) with 95% confidence intervals (95% CIs). One thousand four hundred and three patients with SARS-CoV-2 infection were admitted to the hospital. At the time of the analysis, the outcome was available for 1376 (98%) of them. Five hundred and eighty-seven patients (42%) received azithromycin and 377 patients (27%) received hydroxychloroquine, alone or in combination. In-hospital mortality was 26%. After the adjusted analysis, azithromycin alone was associated with lower mortality (OR 0.60, 95% CI 0.42-0.85) compared to no treatment. Hydroxychloroquine alone (OR 0.76, 95% CI 0.53-1.08) and the combination of azithromycin and hydroxychloroquine (OR 1.13, 95% CI 0.77-1.69) were not associated with hospital mortality. In this cohort of patients, azithromycin alone was associated with lower hospital mortality but hydroxychloroquine was not associated with increased or reduced mortality. While we await randomized clinical trials, these data support the use of azithromycin in novel coronavirus disease 2019 (COVID-19) and can contribute to better understanding of its role in further meta-analyses.
| S-EPMC7563535 | biostudies-literature
Project description:BackgroundChloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.Patients and methodsFrench Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.ResultsSix patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.ConclusionDespite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
| S-EPMC7102549 | biostudies-literature
Project description:Introduction: Severe COVID-19 pneumonia has two phases that are not mutually exclusive. Repurposed drugs target only one phase and the association of combination therapy to survival is unknown. Objective: To determine the association of hydroxychloroquine, azithromycin, and methylprednisolone versus methylprednisolone only to in hospital survival. Methods: This is a secondary analysis of a retrospective cohort of patients admitted for severe covid-19 in 13 hospitals in New Jersey, United States from March-June 2020. Propensity score match with 11 variables was constructed between those who received no methylprednisolone and methylprednisolone. Multivariate Cox regression was used for risk of in hospital mortality. Measurements and main results: There were 759 patients, 380 in no methylprednisolone and 379 with methylprednisolone. Multivariate Cox regression shows that methylprednisolone, hydroxychloroquine, and azithromycin had prolonged survival compared to methylprednisolone alone [HR 0.45 (95% CI 0.22,0.91 p < 0.03)]. In patients who received hydroxychloroquine and azithromycin, those who also received high dose methylprednisolone were associated with worse survival compared to those who received low dose methylprednisolone (HR = 1.642; 95% CI 1.053 to 2.562; p = 0.0287). Nursing home residents [HR 2.77 (95% CI 1.67, 4.59 p < 0.0001)], coronary artery disease [HR 2.93 (95% CI 1.31, 3.15 p = 0.001), and invasive mechanical ventilation [HR 3.02 (95% CI 1.71,5.34 p = 0.0001)] were independently associated with worse survival. Conclusion: Combination therapy was associated with improved survival compared to monotherapy. However, nursing home residents, coronary artery disease, and mechanical ventilation were independently associated with mortality. Larger randomized controlled studies are needed to confirm conclusions.
| S-EPMC9551186 | biostudies-literature
Project description:Recent small-scale clinical trials have shown promising results in the use of hydroxychloroquine, an FDA approved anti-malaria drug, for the treatment of COVID-19. However, large scale, randomized and double-blind clinical trials are needed to confirm the safety and efficacy of hydroxychloroquine in COVID-19 patients. Here, we review the progress of using hydroxychloroquine or chloroquine as anti-viral agents, failed clinical trials of chloroquine in treatment of dengue virus and influenza infection, and especially the mechanism of azithromycin in inhibiting viral replication, so as to shed light on the ongoing clinical trials and further researches of hydroxychloroquine on SARS-CoV-2 infected patients.
| S-EPMC7426511 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.
| S-EPMC7987362 | biostudies-literature
Project description:The ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn the attention of researchers and clinicians from several disciplines and sectors who are trying to find durable solutions both at preventive and treatment levels. To date, there is no approved effective treatment or vaccine available to control the coronavirus disease-2019 (COVID-19). The preliminary in vitro studies on viral infection models showed potential antiviral activities of type I and III interferons (IFNs), chloroquine (CQ)/hydroxychloroquine (HCQ), and azithromycin (AZM); however, the clinical studies on COVID-19 patients treated with CQ/HCQ and AZM led to controversies in different regions due to their adverse side effects, as well as their combined treatment could prolong the QT interval. Interestingly, the treatment with type I IFNs showed encouraging results. Moreover, the different preliminary reports of COVID-19 candidate vaccines showcase promising results by inducing the production of a high level of neutralizing antibodies (NAbs) and specific T cell-mediated immune response in almost all participants. The present review aims to summarize and analyze the recent progress evidence concerning the use of IFNs, CQ/HCQ, and AZM for the treatment of COVID-19. The available data on immunization options to prevent the COVID-19 are also analyzed with the aim to present the promising options which could be investigated in future for sustainable control of the pandemic.
| S-EPMC7831445 | biostudies-literature