Hydroxychloroquine For Treatment Of COVID-19 Research Articles

Laser liquid ablation for silver nanoparticles synthesis and conjugation with hydroxychloroquine for Covid-19 treatment

Synthesis, characterization, and anchorage studies of pristine silver nanoparticles were achieved. That would later be followed by the conjugation of the synthesized silver nanoparticles with hydroxychloroquine, a compound that is commonly identified as active against plasmodium, a malaria-causing agent. The synthesis of the pristine silver nanoparticles was achieved through laser ablation, a physical method. To achieve different concentrations and sizes of the nanoparticles, various parameters such as time and pulse repetition frequencies were varied. The base medium of the ablation was distilled water of 10 ml for every process of ablation. The laser ablation technique used proved effective in the production of silver nanoparticles spherical in shape and of the size range between 16 nm and 30 nm as deduced from Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) characterization techniques. EDS analysis confirmed the presence of AgNPs in the synthesized solution of silver nanoparticles, while the UV–Vis results showed that the absorption peak of AgNPs occurred at 403 nm. Through these findings, the use of laser ablation, a physical technique in the synthesis of AgNPs, is shown to be cost-effective and environmentally friendly with the properties of the nanoparticles proving to be effective for biomedical applications later in this work.

COVID-19 pharmaceuticals in aquatic matrices: The threatening effects over cyanobacteria and microalgae

Water contamination by pharmaceuticals is a global concern due to their potential negative effects on aquatic ecosystems and human health. This study examined the presence of three repositioned drugs used for COVID-19 treatment: azithromycin (AZI), ivermectin (IVE) and hydroxychloroquine (HCQ) in water samples collected from three urban rivers in Curitiba, Brazil, during August and September 2020. We conducted a risk assessment and evaluated the individual (0, 2, 4, 20, 100 and 200 μg.L−1) and combined (mix of the drugs at 2 μg.L−1) effects of the antimicrobials on the cyanobacterium Synechococcus elongatus and microalga Chlorella vulgaris. The liquid chromatography coupled to mass spectrometry results showed that AZI and IVE were present in all collected samples, while HCQ occurred in 78 % of them. In all the studied sites, the concentrations found of AZI (up to 2.85 μg.L−1) and HCQ (up to 2.97 μg.L−1) represent environmental risks for the studied species, while IVE (up to 3.2 μg.L−1) was a risk only for Chlorella vulgaris. The hazard quotients (HQ) indices demonstrated that the microalga was less sensitive to the drugs than the cyanobacteria. HCQ and IVE had the highest values of HQ for the cyanobacteria and microalga, respectively, being the most toxic drugs for each species. Interactive effects of drugs were observed on growth, photosynthesis and antioxidant activity. The treatment with AZI + IVE resulted in cyanobacteria death, while exposure to the mixture of all three drugs led to decreased growth and photosynthesis in the cells. On the other hand, no effect on growth was observed for C. vulgaris, although photosynthesis has been negatively affected by all treatments. The use of AZI, IVE and HCQ for COVID-19 treatment may have generated surface water contamination, which could increased their potential ecotoxicological effects. This raises the need to further investigation into their effects on aquatic ecosystems.

COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats.

Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10mg/kg/day) or captopril (10mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.

Hydroxychloroquine for COVID-19: Variation in Regional Political Preferences Predicted New Prescriptions after President Trump's Endorsement.

On March 19, 2020, President Donald Trump endorsed using hydroxychloroquine for COVID-19 treatment despite inconclusive evidence of the drug's effectiveness. This study sought to understand the influence of political preferences on prescription uptake by quantifying the relationship between a geographic area's partisan leaning and hydroxychloroquine prescription rates following Trump's endorsement. We analyzed hydroxychloroquine prescriptions filled in 205 continental US designated market areas (DMAs) between March 1, 2018, and July 31, 2020, and the percentage of votes for Donald Trump in the 2016 presidential election in each DMA. We estimated associations by using an empirical strategy resembling a difference-in-differences estimation. Before President Trump's endorsement, mean weekly hydroxychloroquine prescription rates were similar across DMAs with the highest and lowest Trump vote percentages (0.56 and 0.49 scripts per 100,000). After Trump's endorsement, although both high- and low-Trump-supportive DMAs experienced sharp increases in weekly hydroxychloroquine prescription rates, results indicated a 1-percentage-point increase in share of Trump votes was associated with 0.013, or 2%, more weekly hydroxychloroquine prescriptions per 100,000 people (b = 0.013, t = 2.20, p = .028). President Trump's endorsement of an untested therapy influenced prescribing behavior, especially when that endorsement aligned with communities' political leanings.

Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial

BackgroundPrevious Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers.MethodsWe conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540.FindingsFrom May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52–1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53–1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57–1·04]).InterpretationIn outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting.FundingCOALITION COVID-19 Brazil and EMS.

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19.

There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic.

Impact of Hydroxychloroquine Treatment of COVID-19 on Cardiac Conduction: The Beat Goes On

Objectives: Our study aimed to investigate the frequency of malignant cardiac arrhythmias in hospitalized patients receiving hydroxychloroquine alone and those receiving a combination of hydroxychloroquine with azithromycin, as well as the quantitative extent of QT prolongation within Tisdale Risk Score (TRS) categories. Background: There have been over 33 million cases of SARS-CoV-2 (COVID-19) resulting in over 600,000 deaths in the United States. As the current COVID-19 pandemic continues, numerous medications have been administered to attempt to treat patients afflicted by the disease. While hydroxychloroquine has been in use for decades for rheumatologic and infectious disease processes, it does have potential cardiotoxicity related to drug-induced QT prolongation. Drug-induced QT prolongation has an increased risk of arrhythmogenicity, potentially progressing into torsades de pointes (TdP) and increased patient mortality. The relationship between QT prolongation and TdP is complex and inexact, but there remains optimism regarding the use of these medications in the treatment of COVID-19 despite limited data on their true efficacy. Methods: We retrospectively identified 75 patients who were admitted with COVID-19 and underwent treatment with hydroxychloroquine for 5 days. The hydroxychloroquine protocol was defined as an initial dose of 400 mg BID for the first day, followed by 400 mg daily for the next 4 days. Baseline demographics, medications, medical histories, lab values, ECG QT intervals, and Tisdale Risk Categories were collected for all patients. Results: Seventy-four (98.7%) patients completed the full course of hydroxychloroquine. There were 41 males (54.7%) and 34 females (45.3%). Average length of stay was 8.9 days (95% CI: 7.5, 10.2). One patient who could not complete the course due to inability to swallow medication tablets. There were no reports of new arrythmias or incidence of torsades de pointes during the study. Seventy-two patients (96%) were taking at least 2 QT prolonging medications. The average corrected QT intervals were as follows: day 1 of admission was 421.62 milliseconds (n = 66, 95% CI: 412.19, 431.05), day 2 was 431.50 ms (n = 30, 95% CI: 416.34, 446.66), day 3 was 433.48 ms (n = 23, 95% CI: 413.34, 453.61), day 4 was 427.59 ms (n = 17, 95% CI: 400.83, 454.35), and day 5 was 444.28 ms (n = 18, 95% CI: 428.43, 460.12). The corrected QT interval prolonged by 22.66 ms from day 1 to day 5 (p = 0.03) in the overall population. Conclusion: There were no patients who experienced arrhythmogenicity or Torsades de Pointes despite a statistically significant increase in QTc intervals after patients received the 5-day course of hydroxychloroquine for treatment of COVID-19.

G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10−3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.

Comparison of Liver Safety of Favipiravir and Hydroxychloroquine in COVID-19 Treatment

Objective: Since the first case from Wuhan, China in December 2019, COVID-19 has spread all over the world and a pandemic was declared by the World Health Organization on January 30, 2020. While there are no specific effective antiviral drugs or vaccines to treat or to prevent COVID-19; favipiravir, hydroxychloroquine and their combination are used […]

Bringing evidence from press release to the clinic in the era of COVID-19.

The urgent need to develop effective therapeutics and disseminate information from clinical studies has led to data from clinical trials being made available by alternate methods prior to peer-reviewed publication, including press releases, social media and pre-print papers. While this allows clinicians more open access to these data, a trust has to be placed with the investigators releasing these data without the availability of scientifically rigorous peer review. The examples of results from trials studying dexamethasone and hydroxychloroquine for treatment of COVID-19 have had contrasting outcomes, including the potential for significant numbers of lives saved with the early release of results from the RECOVERY trial studying dexamethasone contrasting with unsubstantiated data being presented from trials studying hydroxychloroquine. Clinicians and researchers must maintain a healthy scepticism when reviewing results prior to peer-reviewed publication, but also consider when these opportunities may allow for early implementation of potentially lifesaving interventions for people infected with COVID-19.

The Role of Hydroxychloroquine in COVID-19 Treatment: A Systematic Review and Meta-Analysis

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google-Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ+AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease. Keywords: Azithromycin, coronavirus outbreaks, pandemic, 2019-nCoV disease

The Role of Hydroxychloroquine in COVID-19 Treatment: A Systematic Review and Meta-Analysis

Objective: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. Methods: We performed a systematic search in PubMed, Scopus, Embase, Cochrane- Library, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. Results: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81–1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91–1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71–1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76–2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). Conclusion: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease. Keywords: Azithromycin, coronavirus outbreaks, pandemic, SARS-CoV-2 disease

Change of opinion on the use of hydroxychloroquine for COVID-19 treatment and prevention

The use of hydroxychloroquine for COVID-19 treatment and prevention should be restricted in both out- and inpatient settings due to the lack of evidence for effectiveness and unfavorable safety profile.

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.

CHLOROQUINE AND HYDROXYCHLOROQUINE: A MAJOR BREAKTHROUGH FOR COVID-19

Coronavirus pandemic or COVID-19 is a global public health emergency at this period. Presently, no pharmacological treatment is known to treat this condition. Hydroxychloroquine (HCQ), a derivative of chloroquine (CQ), was first synthesized in 1946 by adding a hydroxyl group to CQ, which is much less toxic than CQ in animal studies. Other than being an anti-malarial drug, it was revealed to have various pharmacological effects and one of those is its anti-viral property. CQ, as well as HCQ, has been used in SARS (Severe Acute Respiratory Syndrome) coronavirus infection due to its antiviral properties. Even though various scientists have considered HCQ as a better therapeutic approach than CQ for the treatment of coronavirus infection, there are various adverse drug reactions associated with HCQ treatment in COVID-19 patients. In this paper, we review the anti-viral mechanism, various adverse drug reactions, and side effects of HCQ for COVID-19 treatment.

CORRIGENDUM to Emergency Approval of Chloroquine and Hydroxychloroquine for Treatment of COVID-19 (updated to Emergency Authorization of Chloroquine and Hydroxychloroquine for Treatment of COVID-19).

CORRIGENDUM to Emergency Approval of Chloroquine and Hydroxychloroquine for Treatment of COVID-19 (updated to Emergency Authorization of Chloroquine and Hydroxychloroquine for Treatment of COVID-19).

Hydroxychloroquine use in the COVID-19 patient.

Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of COVID-19 are rapidly evolving. To date, there is no evidence from randomized controlled trials that HCQ, or any single therapy, improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Use of HCQ in patients with COVID-19 is being investigated for prophylaxis, postexposure prophylaxis, and treatment.

The Risks of Prescribing Hydroxychloroquine for Treatment of COVID-19—First, Do No Harm

Research Letter Internet Searches for Unproven COVID-19 Therapies in the United States Michael Liu, AB; Theodore L. Caputi, MPH; Mark Dredze, PhD; Aaron S. Kesselheim, MD, JD, MPH; John W. Ayers, PhD, MA