The Outcome of Hydroxychloroquine in Patients Treated for COVID-19: Systematic Review and Meta-Analysis

Abstract

Background. The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in an unprecedented public health challenge worldwide. Despite urgent and extensive global efforts, the existing evidence is inconclusive regarding the medications used for the treatment of COVID-19. Purpose. To generate an up-to-date evidence for the clinical safety and efficacy of hydroxychloroquine (HCQ) with or without azithromycin (AZ) among patients treated for COVID-19. Data Source. PubMed, Cochrane CENTRAL, LITCOVID, Web of Science, SCOPUS, BioRxiv, Embase, MedRxiv, and Wiley online library were searched from 2019/12/30 to 2020/05/23. Study Selection. Three investigators assessed the quality of the studies. Data Extraction. Data about study characteristics, effect estimates, and the quality of the studies were extracted by two independent reviewers and cross-checked by the third reviewer. Data Synthesis. The data of 6,782 (HCQ group, 3623; HCQ + AZ group, 1,020; control group, 2139) participants were included. HCQ was compared with standard care for virologic efficacy, disease progression, mortality, and adverse effects. HCQ was also compared with HCQ + AZ for QTc prolongation, admission to the intensive care unit, and mortality. The study found HCQ did not alter the rate of virologic cure (OR = 0.78; 95% CI: 0.39–1.56) and the risk of mortality (OR = 1.26; 95% CI: 0.66–2.39). The pooled prevalence for mortality was 5.8% (95% CI: 0.9%–10.8%). Moreover, HCQ did not impact disease progression (OR = 0.9; 95% CI: 0.36–2.29) but resulted in a higher risk of adverse effects (OR = 2.35; 95% CI: 1.15–4.8). HCQ was also compared against HCQ + AZ, and no difference was observed in QTc prolongation above 500 ms (OR = 1.11; 95% CI: 0.54–2.28), admission to the intensive care unit (OR = 0.92; 95% CI: 0.52–1.63), and mortality (OR = 0.88; 95% CI: 0.55–1.43). However, in the analysis of single-arm studies, about 11.2% (95% CI: 7.0%–15.5%) of patients have developed an absolute increase of QTc greater than 500 ms, and 4.1% (95% CI: 1.1%–7.1%) of patients discontinued their medication. Conclusion. This meta-analysis and systematic review, which included a limited number of poorly designed studies of patients with COVID-19, revealed HCQ is intolerable, unsafe, and not efficacious. Similarly, HCQ + AZ combination was not different from HCQ alone in curbing mortality and ICU admission.

Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia

“…However, no impact of HCQ on mortality or reducing the risk of clinical worsening of the disease was reported. Another systematic review and meta-analysis by Mega et al [35] also confirmed that HCQ does not improve viral clearance, disease worsening, and mortality rates. It rather showed that mortality rates were slightly higher in patients treated with HCQ, several of whom had to stop taking HCQ-based treatment due to severe adverse drug reactions.…”

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

“…As this drug is a well-established inhibitor of autophagy, we reasoned that alterations of this important biological process might have a role in the increased severity of the clinical phenotypes of SARS-CoV-2 infection in patients with the TLR3_L412F polymorphism. Notably, beside being entirely ineffective at changing the clinical evolution of COVID-19, which led to retraction of the paper reporting the clinical trial [31], HCQ may have been responsible for reportedly increased fatality rates among patients treated with this drug [32,33]. Poly(I:C) stimulation of the TLR3 receptor has already been shown to stimulate autophagy [30].…”

Molecular mechanism, diagnosis, and potential treatment for novel coronavirus (COVID-19): a current literature review and perspective

“… Therapeutic drug Common name Target Comments/significance References 1 Chloroquine derives hydroxy-chloroquine Aralen/plaquenil SARS-CoV 2 More useful to improve clinical and virological outcomes. But reduce mortality Million et al ( 2020 ), Pathak et al ( 2020 ), Siemieniuk et al ( 2020 ) 2 Dexamethasone Decadron SARS-CoV 2 Risk of mortality and benefits for severing clinical condition patients Abeldano Zuniga et al ( 2020 ), Siemieniuk et al ( 2020 ) 3 Lopinavir-Ritonavir Kaletra HIV, SARS-CoV 2 Risk of mortality, adverse events Abeldano Zuniga et al ( 2020 ), Siemieniuk et al ( 2020 ) 4 Remdesivir with placebo Veklury Ebola, COVID-19 Risk of mortality Abeldano Zuniga et al ( 2020 ), Siemieniuk et al ( 2020 ) 5 Hydroxy-chloroquine with azithromycin Aralen/plaquenil and zitromax SARS-CoV 2 Not alter the rate of risk of virologic cure and risk of mortality, Not different from hydroxy-chloroquine alone Ayele Mega et al ( 2020 ), Chen et al ( 2020c ), (Tang et al ( 2020 ), Fiolet et al ( 2020 ), Abeldano Zuniga et al ( 2020 ), Siemieniuk et al ( 2020 ) 6 Tolicizumab Actemra …”