Do we have enough evidence to use chloroquine/hydroxychloroquine as a public health panacea for COVID-19?
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ABSTRACT:
SUBMITTER: Palmeira VA
PROVIDER: S-EPMC7199295 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Do we have enough evidence to use chloroquine/hydroxychloroquine as a public health panacea for COVID-19?
Palmeira Vitória Andrade VA Costa Larissa Braga LB Perez Lucas Giandoni LG Ribeiro Victor Teatini VT Lanza Katharina K Silva Ana Cristina Simões E ACSE
Clinics (Sao Paulo, Brazil) 20200508
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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: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:Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.
| S-EPMC7244425 | biostudies-literature
Project description:Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.
| S-EPMC7792551 | biostudies-literature
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.
| S-EPMC7177204 | biostudies-literature
Project description: Not available
| S-EPMC8094389 | biostudies-literature
Project description:The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.
| S-EPMC7202851 | biostudies-literature
Project description:BackgroundMexican state governments' actions are essential to control the COVID-19 pandemic within the country. However, the type, rigor and pace of implementation of public policies have varied considerably between states. Little is known about the subnational (state) variation policy response to the COVID-19 pandemic in Mexico.Material and methodsWe collected daily information on public policies designed to inform the public, as well as to promote distancing, and mask use. The policies analyzed were: School Closure, Workplace Closure, Cancellation of Public Events, Restrictions on Gatherings, Stay at Home Order, Public Transit Suspensions, Information Campaigns, Internal Travel Controls, International Travel Controls, Use of Face Masks We use these data to create a composite index to evaluate the adoption of these policies in the 32 states. We then assess the timeliness and rigor of the policies across the country, from the date of the first case, February 27, 2020.ResultsThe national average in the index during the 143 days of the pandemic was 41.1 out of a possible 100 points on our index. Nuevo León achieved the highest performance (50.4); San Luis Potosí the lowest (34.1). The differential between the highest versus the lowest performance was 47.4%.ConclusionsThe study identifies variability and heterogeneity in how and when Mexican states implemented policies to contain COVID-19. We demonstrate the absence of a uniform national response and widely varying stringency of state responses. We also show how these responses are not based on testing and do not reflect the local burden of disease. National health system stewardship and a coordinated, timely, rigorous response to the pandemic did not occur in Mexico but is desirable to contain COVID-19.
| S-EPMC8168889 | biostudies-literature
Project description:ObjectivesWe critically evaluated the quality of evidence and quality of harm reporting in clinical trials that evaluated the effectiveness of hydroxychloroquine (HCQ) or chloroquine (CQ) for the treatment of coronavirus disease 2019 (COVID-19).Study design and settingScientific databases were systematically searched to identify relevant trials of HCQ/CQ for the treatment of COVID-19 published up to 10 September 2020. The Cochrane risk-of-bias tools for randomized trials and non-randomized trials of interventions were used to assess risk of bias in the included studies. A 10-item Consolidated Standards of Reporting Trials (CONSORT) harm extension was used to assess quality of harm reporting in the included trials.ResultsSixteen trials, including fourteen randomized trials and two non-randomized trials, met the inclusion criteria. The results from the included trials were conflicting and lacked effect estimates adjusted for baseline disease severity or comorbidities in many cases, and most of the trials recruited a fairly small cohort of patients. None of the clinical trials met the CONSORT criteria in full for reporting harm data in clinical trials. None of the 16 trials had an overall 'low' risk of bias, while four of the trials had a 'high', 'critical', or 'serious' risk of bias. Biases observed in these trials arise from the randomization process, potential deviation from intended interventions, outcome measurements, selective reporting, confounding, participant selection, and/or classification of interventions.ConclusionIn general, the quality of currently available evidence for the effectiveness of CQ/HCQ in patients with COVID-19 is suboptimal. The importance of a properly designed and reported clinical trial cannot be overemphasized amid the COVID-19 pandemic, and its dismissal could lead to poorer clinical and policy decisions, resulting in wastage of already stretched invaluable health care resources.
| S-EPMC7524513 | biostudies-literature
Project description:In December 2019, a severe outbreak of a novel coronavirus (COVID-19) occurred in the whole world, posing a great threat to people's health. With the outbreak and development of the epidemic, how to improve the cure rate, find effective drugs against this virus, has been the most urgent problem. Chloroquine (CQ) was verified effective against COVID-19 in vitro. As CQ's analogue, hydroxychloroquine (HCQ) was also reminded as a potential candidate for treating COVID-19. This review summarizes the latest clinical trials of CQ and HCQ against COVID-19 and its therapeutic regimen in China aiming to share their current usage to the whole world and provide insight into its appropriate future use in the treatment of COVID-19. Through searching the CNKI and Wangfang databases in Chinese language and PubMed, EMBASE, and Ovid databases in English language to identify published reports with the keywords including "coronavirus/COVID, chloroquine, hyroxychloroquine" in alone or combined, we found out the potential preclinical or clinical evidence for using CQ and HCQ against COVID-19. Consequently, we also searched the website of Chinese Clinical Trial Registry (http://www.chictr.org.cn/) till the day on 27th, June, 2020. This review found that there are 23 programs aimed to treat the different phases under COVID-19 pipeline in clinic with CQ and HCQ, totally. The inclusion criteria, exclusion criteria and therapeutic regimen were all shared to consult. Among them, seven have been canceled due to lack of patients or other objective factors. There are two trials have completed, which the potential relationship between usage and adverse reactions was discussed emphatically. Through literature research, we suggested that paid close attention to retinal toxicity and ophthalmologic adverse symptom of CQ and HCQ. And the outcome of HCQ in clinic shows better than CQ especially in protective effect with low dosage.
| S-EPMC7412992 | biostudies-literature