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Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update.

ABSTRACT: 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.

SUBMITTER: Joshi G

PROVIDER: S-EPMC7959684 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update.

Project description:As the time for finding a definitive and safe cure as a vaccine for novel Corona Virus Disease 2019 (Covid-19) is still far, there is need to study in depth about the other potential drugs, which can save millions of lives due to Covid-19 pandemic. Right at the center of the debate is the use of drug "Hydroxychloroquine" as a prophylaxis as well as a treatment strategy against Covid-19 in conjunction with azithromycin. In this review, we will study the cellular and molecular aspects of hydroxychloroquine, which had driven its use in Covid-19 patients, as well as its chemistry and pharmacokinetics along with clinical trials going on worldwide using hydroxychloroquine against Covid-19.

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Update Alert: Hydroxychloroquine or Chloroquine for the Treatment or Prophylaxis of COVID-19.

Project description: Not available

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Update Alert 2: Hydroxychloroquine or Chloroquine for the Treatment or Prophylaxis of COVID-19.

Project description: Not available

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Update Alert 3: Hydroxychloroquine or Chloroquine for the Treatment or Prophylaxis of COVID-19.

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Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19.

Project description:PURPOSE:To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MATERIALS AND METHODS:MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. RESULTS:Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two 'some concerns' and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. CONCLUSIONS:Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed.

| S-EPMC7351664 | biostudies-literature

Exploring the Biological Mechanisms of Severe COVID-19 in the Elderly: Insights from an Aged Mouse Model

Project description:Definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain confused. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform.

2024-08-25 | GSE274784 | GEO

Hydroxychloroquine can potentially interfere with immune function in COVID-19 patients: Mechanisms and insights.

Project description:The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.

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[COVID-19 Update].

Project description: Not available

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Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients.

Project description:Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient's plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.

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Exploring status of emergency drugs and vaccine development in Covid-19 pandemic: an update.

Project description:COVID-19 outburst initiated from the city of Wuhan in China in December 2019 and has been declared as a public health emergency of international concern. This pandemic portrays a spectrum of clinical complications, primarily affecting the respiratory system reported to be caused by a pathogen SARS-CoV-2 belonging to the family of beta coronavirus. Currently, the main objective of the government authorities of all affected countries and research organizations is to find a potential solution in the form of a pharmacological intervention or a vaccination to eradicate the disease and to have a long-term solution to deal with the pandemic. A multitude of anti-viral regimens is proposed based on the repurposing of currently available drugs for other issues or the compassionate use of drugs to immediately control and optimize the healthcare facilities. Meanwhile, a number of agencies are proposing new drug candidates to recreate the possibility of treating the disease. Similarly, a lot of research work is going on worldwide for the development of vaccination. Currently, a good number of candidates has finally reached the borders of Clinical Trials and are expected to be launched as soon as possible. However, the regulatory framework and authorization of these candidates is the most significant aspect of the whole scenario, which needs a specific set of time for validation purposes. The present work is widely focused on the general aspects of COVID-19 and the regulatory landscape for the emergency authorization of repurposed drug candidates, compassionate use of drugs, investigational entities, and vaccine development worldwide.Supplementary informationThe online version contains supplementary material available at 10.1007/s13337-021-00684-5.

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