Hydroxychloroquine In Coronavirus Disease 2019 Research Articles

Articles That May Change Your Practice: Current Evidence for Coronavirus Disease 2019 Therapies

Articles That May Change Your Practice: Current Evidence for Coronavirus Disease 2019 Therapies

Hydroxychloroquine in COVID-19: therapeutic promises, current status, and environmental implications.

The outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the entire world with its infectious spread and mortality rate. The severe cases of coronavirus disease 2019 (COVID-19) are characterized by hypoxia and acute respiratory distress syndrome. In the absence of any specific treatment, just the preventive and supportive care options are available. Therefore, much focus is given to assess the available therapeutic options not only to avoid acute respiratory failure and hypoxia but also to reduce the viral load to control the severity of the disease. The antimalarial drug hydroxychloroquine (HCQ) is among the much-discussed drugs for the treatment and management of COVID-19 patients. This article reviews the therapeutic potential of HCQ in the treatment of COVID-19 based on the available in vitro and clinical evidence, current status of registered HCQ-based clinical trials investigating therapeutic options for COVID-19, and environmental implications of HCQ.

PIN3 Chloroquine and Hydroxychloroquine in COVID-19 with or without Azithromycin: A Systematic Review of in Vitro and Clinical Studies

Coronavirus disease 2019 (COVID-19) is an international public health emergency and there is a critical need to identify effective drugs. This document is a systematic review of published clinical experiences and in vitro studies using chloroquine (CQ) or hydroxychloroquine (HCQ) with or without Azithromycin for COVID-19 treatment. A systematic literature review was performed using Pubmed, Web of Science, Chinese Web of Knowledge and Google Scholar and clinical trials’ registries from inception to April 2, 2020. We included 10 relevant articles; 4 in vitro studies, 2 RCTs, 3 observational studies and 1 editorial reporting pooled results from unpublished clinical trials. In vitro studies showed that CQ and HCQ reduce SARS-CoV-2 replication. Regarding clinical trials, only few records were exploitable. Moreover, available data come mainly from observational studies or from very small sample controlled trials. As in RCTs, observational studies showed contradictory results regarding the efficacy of HCQ with or without azithromycin and had many limitations. Therefore, there is no high-quality evidence that these treatments improve outcomes in COVID-19. The results described in some trials can justify a further exploration either within the framework of ethically approved RCTs or Monitored Emergency Use of Unregistered and Investigational Interventions if RCTs are not possible.

Hypothesis: What is the Best We Can Do with Hydroxychloroquine for COVID-19?

There are widespread anecdotal reports of seemingly successful treatment among the early (three to seven days from symptoms) stage coronavirus disease 2019 (COVID-19) patients with the drug hydroxychloroquine (HCQ), and randomized placebo-controlled trials of HCQ in outpatient settings are underway. In this note, we (1) report observational evidence and present scientific reasoning as to why early treatment with HCQ may succeed while treatment later in the disease progression is likely to fail and (2) hypothesize a public health regime under which HCQ may be used to mitigate the impact of the current pandemic.

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials.

IntroductionMany concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19).ObjectivesThe purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis.MethodsRandomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers.ResultsWe identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003).ConclusionsHCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies.Electronic supplementary materialThe online version of this article (10.1007/s00228-020-02962-5) contains supplementary material, which is available to authorized users.

A Call for Pediatric COVID-19 Clinical Trials.

* Abbreviations: COVID-19 — : coronavirus disease 2019 CQ — : chloroquine HCQ — : hydroxychloroquine SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Should children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection receive antiviral therapy? If so, what should we give, to which children, and for what disease severity? Despite brisk scientific progress elucidating the biology and transmission of SARS-CoV-2, and numerous adult trials testing antiviral therapies, we may pass the formative stages of this pandemic without defining antiviral agents’ appropriate role in pediatric management. We urgently need pediatric clinical trials to establish the efficacy, safety, and pharmacokinetics of the most promising experimental and repurposed coronavirus disease 2019 (COVID-19) therapies proposed to date.1 Researchers of early reports show that pediatric SARS-CoV-2 infection tends to be mild but that some children develop severe disease.2 In these reports, researchers highlight differences between pediatric and adult COVID-19 and argue that risk/benefit calculations of therapies derived from adult trials cannot be readily extrapolated to children. Gaps in our knowledge of pediatric COVID-19 further complicate assessments of risk and benefit. To date, we have a limited understanding of viral kinetics or immune responses in children, what factors predispose some children to severe disease, or how these variables affect responses to therapies. We have equally limited comprehension of how SARS-CoV-2 affects children with primary immunodeficiencies, illnesses requiring immune-compromising therapies, or other complex conditions. Nonetheless, treatment planning for severe pediatric cases, even if they will be few, has spurred children’s hospitals to develop algorithms that include antiviral agents, such as remdesivir, chloroquine (CQ), and … Address correspondence to Jeffrey I. Campbell, MD, Division of Infectious Diseases, Boston Children’s Hospital, 333 Longwood Ave, 6th Floor, Boston, MA 02115. E-mail: jeffrey.campbell{at}childrens.harvard.edu

Use of Chloroquine and Hydroxychloroquine in COVID-19 and Cardiovascular Implications: Understanding Safety Discrepancies to Improve Interpretation and Design of Clinical Trials.

Author(s): Oren, Ohad; Yang, Eric H; Gluckman, Ty J; Michos, Erin D; Blumenthal, Roger S; Gersh, Bernard J

Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis.

BackgroundDuring the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes.MethodsMultiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model.ResultsTwelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance.ConclusionsHCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.

Cardiovascular disease management during the coronavirus disease 2019 pandemic.

Based on clinical presentation, pathophysiology, high infectivity, high cardiovascular involvement, and therapeutic agents with cardiovascular toxicity of coronavirus disease 2019 (COVID-19), regular cardiovascular treatment is being changing greatly. Despite angiotensin-converting enzyme 2 serving as the portal for infection, the continuation of clinically indicated renin-angiotensin-aldosterone blockers is recommended according to the present evidence. Fibrinolytic therapy can be considered a reasonable option for the relatively stable ST segment elevation myocardial infarction (STEMI) patient with suspected or known COVID-19. However, primary percutaneous coronary intervention is still the standard of care in patients with definite STEMI if personal protective equipment is available and cardiac catheterization laboratory has a good infection control. In patients with elevated cardiac enzymes, it is very important to differentiate patients with Type 2 myocardial infarction or myocarditis from those with true acute coronary syndromes because invasive percutaneous intervention management in the former may be unnecessary, especially if they are hemodynamically stable. Finally, patients with baseline QT prolongation or those taking QT prolonging drugs must be cautious when treating with lopinavir/ritonavir and hydroxychloroquine for COVID-19.