Can we use hydroxychloroquine to treat COVID-19 now?
Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC7834540 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Can we use hydroxychloroquine to treat COVID-19 now?
Chen Jun J Liu Danping D Yin Lin L Zhang Lijun L Lu Hongzhou H
International journal of antimicrobial agents 20210101 1
Similar Datasets
Project description:ImportanceThe COVID-19 pandemic has been notable for the widespread dissemination of misinformation regarding the virus and appropriate treatment.ObjectiveTo quantify the prevalence of non-evidence-based treatment for COVID-19 in the US and the association between such treatment and endorsement of misinformation as well as lack of trust in physicians and scientists.Design, setting, and participantsThis single-wave, population-based, nonprobability internet survey study was conducted between December 22, 2022, and January 16, 2023, in US residents 18 years or older who reported prior COVID-19 infection.Main outcome and measureSelf-reported use of ivermectin or hydroxychloroquine, endorsing false statements related to COVID-19 vaccination, self-reported trust in various institutions, conspiratorial thinking measured by the American Conspiracy Thinking Scale, and news sources.ResultsA total of 13 438 individuals (mean [SD] age, 42.7 [16.1] years; 9150 [68.1%] female and 4288 [31.9%] male) who reported prior COVID-19 infection were included in this study. In this cohort, 799 (5.9%) reported prior use of hydroxychloroquine (527 [3.9%]) or ivermectin (440 [3.3%]). In regression models including sociodemographic features as well as political affiliation, those who endorsed at least 1 item of COVID-19 vaccine misinformation were more likely to receive non-evidence-based medication (adjusted odds ratio [OR], 2.86; 95% CI, 2.28-3.58). Those reporting trust in physicians and hospitals (adjusted OR, 0.74; 95% CI, 0.56-0.98) and in scientists (adjusted OR, 0.63; 95% CI, 0.51-0.79) were less likely to receive non-evidence-based medication. Respondents reporting trust in social media (adjusted OR, 2.39; 95% CI, 2.00-2.87) and in Donald Trump (adjusted OR, 2.97; 95% CI, 2.34-3.78) were more likely to have taken non-evidence-based medication. Individuals with greater scores on the American Conspiracy Thinking Scale were more likely to have received non-evidence-based medications (unadjusted OR, 1.09; 95% CI, 1.06-1.11; adjusted OR, 1.10; 95% CI, 1.07-1.13).Conclusions and relevanceIn this survey study of US adults, endorsement of misinformation about the COVID-19 pandemic, lack of trust in physicians or scientists, conspiracy-mindedness, and the nature of news sources were associated with receiving non-evidence-based treatment for COVID-19. These results suggest that the potential harms of misinformation may extend to the use of ineffective and potentially toxic treatments in addition to avoidance of health-promoting behaviors.
| S-EPMC10542734 | biostudies-literature
Project description:Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.
| S-EPMC10016880 | biostudies-literature
Project description:The ongoing pandemic of COVID-19 infection demands efforts to reduce spread. In order to eradicate an infectious disease, a method of prevention with low social cost is the most effective way. While we wait for new therapies and a vaccine, we are proposing a solution based on the existing knowledge in biomedical sciences. Here we propose to use low doses of hydroxychloroquine (50-100 mg daily orally) and intranasal interferon alpha-2b (IFN α-2b) spray (0.5 × 106 IU twice daily) for the prophylaxis of COVID-19. Although there are ongoing clinical trials to test the efficacy of hydroxychloroquine for prophylaxis, there has not been any proposal to test the efficacy of IFN α-2b together with hydroxychloroquine to increase protection against COVID-19. Since the two act on two different mechanisms, we strongly believe that the two could have additive effects in prophylaxis against COVID-19. We recommend using a randomized control study to prove efficacy and safety.
| S-EPMC7239001 | biostudies-literature
Project description:AimTo assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19.MethodsWe utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities.Results36 patients received hydroxychloroquine and were age- and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: -1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: -1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 ± 26 ms to 464 ± 32 ms (mean±SD) among patients receiving hydroxychloroquine with or without azithromycin.ConclusionThis study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.
| S-EPMC7403006 | 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:In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 μg of chloroquine or 7.99 μg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.
| S-EPMC8821864 | biostudies-literature
Project description:Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. We examined the effects of HCQ alone, and in combination with azithromycin, in a hospitalized COVID-19 positive, United States (US) Veteran population using a propensity score adjusted survival analysis with imputation of missing data. From March 1, 2020 through April 30, 2020, 64,055 US Veterans were tested for COVID-19 based on Veteran Affairs Healthcare Administration electronic health record data. Of the 7,193 positive cases, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and an increased risk of intubation when used in combination with azithromycin [Hazard Ratio (95% Confidence Interval): 1.55 (1.07, 2.24)]. In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treating patients hospitalized with COVID-19 using a national sample of the US Veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.
| S-EPMC8384407 | biostudies-literature
Project description:The risk of fatal arrhythmias is the major concern for using chloroquine (CQ) or hydroxychloroquine (HCQ) to treat coronavirus disease 2019 (COVID-19), but the reported number of life-threatening arrhythmic events or deaths is relatively small. The objective of this study was to assess the arrhythmogenic risk of these two drugs using a multiscale heart simulation, which allows testing even at high concentrations, including those that cause fatal arrhythmias. We measured the inhibitory action of CQ, HCQ, and HCQ with 30 μM azithromycin (AZ) on six ion currents (fast [INa] and late [INa,L] components of the sodium current, L-type calcium current [ICa,L], rapid [IKr/hERG], and slow [IKs] components of delayed rectifier potassium, and inward rectifier potassium [IK1]) over a wide range of concentrations using the automated patch-clamp system. Using the concentration-inhibition relationship that was thus obtained, we simulated the drug effects while increasing the concentration until the life-threatening arrhythmia, torsade de pointes (TdP), was observed. The obtained threshold concentrations for TdP were 12.5, 35, and 22.5 μM for CQ, HCQ, and HCQ with AZ, respectively. Adding therapeutic concentrations of mexiletine or verapamil successfully prevented the occurrence of TdP, and verapamil was more effective. CQ, HCQ, and HCQ with AZ thresholds for TdP were larger than both antiviral concentrations that were reported by in vitro experiments and free plasma concentrations that were attained by the clinically used dosage. The current simulation data provided a safety margin to the currently used clinical dose for CQ and HCQ/AZ. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Despite the potent in vitro antiviral effect, clinical trials have failed to show the therapeutic effects of chloroquine (CQ) and hydroxychloroquine (HCQ)/azithromycin (AZ) to treat coronavirus disease 2019. Torsadogenic potentials may limit the dosage of these drugs, but the reported incidence of fatal arrhythmias is rare. WHAT QUESTION DID THIS STUDY ADDRESS? Our objective was to assess the arrhythmogenicity of CQ and HCQ/AZ over a wide range of drug concentrations using a multiscale heart simulation. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our study showed that CQ and HCQ/AZ do not induce fatal arrhythmias even at concentrations much higher than in vitro antiviral half-maximal effective concentration (EC50 ) values at which QT prolongation exceeds 150 ms. We also found that estimated free plasma concentrations of CQ and HCQ/AZ achieved by currently used dosing protocols are lower than the antiviral EC50 for these drugs. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Our simulation data provided a safety margin to the currently used clinical dose for CQ and HCQ/AZ.
| S-EPMC8212750 | biostudies-literature
Project description:Hydroxychloroquine (HCQ) has been implicated in antiviral activity in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still controversy about whether HCQ should be used for coronavirus disease 2019 (COVID-19) patients due to the conflicting results in different clinical trials. To systematically assess the benefits and harms of HCQ for the treatment of COVID-19. Data sources were systematically searched from Pubmed, Biorxiv, ChiCTR, Clinicalrials.gov , and the Cochrane library of RCTs for studies published from inception to June 1, 2020, to obtain any possible inclusion. This meta-analysis of inclusion criteria was directed on the basis of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). Pooled studies by the title and abstract were screened and removed in the light of meta-analysis by two reviewers. Seven studies involving 851 participants with COVID-19 were eligible for analysis. There was no significant difference in RT-PCR negative conversion between HCQ group and standard treatment (ST) group (RR = 1.11, 95% CI = 0.77-1.59, P = 0.591). The rate of exacerbated pneumonia on chest CT in HCQ group was lower than that in ST group (RR = 0.44, 95% CI = 0.20-0.94, P = 0.035). There was no statistical difference in progressed illness between the HCQ group and the ST group (RR = 0.66, 95% CI = 0.18-2.43, P = 0.530). Death (RR = 1.92, 95% CI = 1.26-2.93, P = 0.003) was distinctly different in HCQ group compared with ST group in the treatment of COVID-19. Our meta-analysis demonstrated that there was no robust evidence to support prescribing HCQ as a treatment for COVID-19.
| S-EPMC7474863 | biostudies-literature
Project description:BackgroundThe COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.MethodsElectronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.ResultsNeither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.ConclusionAdministration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.
| S-EPMC7968637 | biostudies-literature