COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology.
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ABSTRACT:
SUBMITTER: White NJ
PROVIDER: S-EPMC7470382 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology.
White Nicholas J NJ Watson James A JA Hoglund Richard M RM Chan Xin Hui S XHS Cheah Phaik Yeong PY Tarning Joel J
PLoS medicine 20200903 9
Nicholas White and coauthors discuss chloroquine and hydroxychloroquine pharmacology in the context of possible treatment of SARS-CoV-2 infection. ...[more]
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Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effects of chloroquine (CQ) and hydroxychloroquine (HCQ) as: an antiviral treatment on death and time to clearance of the virus from clinical samples and recovery in people with COVID‐19; a prophylactic treatment on prevention of COVID‐19 in people at risk of SARS‐CoV‐2 exposure; a prophylactic treatment on prevention of COVID‐19 in people who have been exposed to SARS‐CoV‐2.
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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
Project description:IntroductionGiven the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug.BackgroundThe in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis.Review resultsLiterature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes.ConclusionAs per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia.How to cite this articleShetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.
| S-EPMC8138637 | biostudies-literature
Project description:The 4-aminoquinolines are weak bases that are completely absorbed from the gastrointestinal tract, sequestered in peripheral tissues, metabolized in the liver to pharmacologically active by-products, and excreted via the kidneys and the feces. The parent drugs and metabolites are excreted with a half-life of elimination of approximately 40 days. However, slow release from sequestered stores of the drugs means that after discontinuation, they continue to be released into the plasma for years. Correct dosing is based on the ideal body weight of the patient, which depends on height. The 4AQs diminish autoimmunity without compromising immunity to infections.
| S-EPMC7122276 | biostudies-literature
Project description:Background and objectivesIn 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 methodsA 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.ResultsA 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.ConclusionsAlthough 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.
| S-EPMC7837044 | biostudies-literature
Project description:BackgroundThere is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.ObjectiveWe performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.MethodsTwo reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.ResultsWe reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.Authors' conclusionThe available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
| S-EPMC7471562 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.
| S-EPMC7184359 | biostudies-literature
Project description:ObjectivesThe emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention.MethodsIn this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0.ResultsThere are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design.ConclusionThere are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.
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Project description:Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients.
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