Efficacy of chloroquine and hydroxychloroquine in treating COVID-19 infection: A meta-review of systematic reviews and an updated meta-analysis

Abstract

Objective To synthesize findings from systematic reviews and meta-analyses on the efficacy and safety of chloroquine (CQ) and hydroxychloroquine (HCQ) with or without Azithromycin for treating COVID-19, and to update the evidence using a meta-analysis. Methods A comprehensive search was carried out in electronic databases for systematic reviews, meta-analyses and experimental studies which investigated the efficacy and safety of CQ, HCQ with or without Azithromycin to treat COVID-19. Findings from the reviews were synthesised using tables and forest plots and the quality effect model was used for the updated meta-analysis. The main outcomes were mortality, the need for intensive care services, disease exacerbation, viral clearance and occurrence of adverse events. Results Thirteen reviews with 40 primary studies were included. Two meta-analyses reported a high risk of mortality, with ORs of 2.2 and 3.0, and the two others found no association between HCQ and mortality. Findings from two meta-analyses showed that HCQ with Azithromycin increased the risk of mortality, with similar ORs of 2.5. The updated meta-analysis of experimental studies showed that the drugs were not effective in reducing mortality (RR 1.1, 95%CI 1.0–1.3, I 2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9–1.4, I 2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5–4.4, I 2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3–5.9, I 2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5–59.9, I 2 = 76.6%). Conclusion There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation. Registration PROSPERO: CRD42020191353.

Assessment of Recovery Time, Worsening, and Death among Inpatients and Outpatients with COVID-19, Treated with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso

“…Our study showed that the time to viral clearance and risk of worsening or transfer to an ICU were not significantly higher or lower in patients who received CQ/HCQ + AZ than in those who did not. Similar results have also been reported in other studies carried out in several countries worldwide (Chen et al, 2021;Chivese et al, 2021;Elavarasi et al, 2020;Eze et al, 2021;Fiolet et al, 2021;Maraolo and Grossi, 2021;Mittal et al, 2021). In consistance with other studies, the overall mortality over our study period was significantly lower in the CQ/HCQ + AZ group (Arshad et al, 2020;Ayerbe et al, 2020;Bernaola et al, 2020;Catteau et al, 2020;Lagier et al, 2020;MILLION et al, 2021;Yu et al, 2020b), albeit the sample selection in our study did not allow for propensity score-adjusted analysis of risk of death, making it difficult to conclude on one direction or the other.…”

Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes

“…Chi et al [ 38 ] reported a network metanalysis of randomized controlled trials showing no differences in terms of mortality or mechanical ventilation use. Moreover, other studies found no differences regarding hospitalization risks in mild COVID-19 cases when comparing usual care or placebo with hydroxychloroquine use, instead, higher levels of side effects were noted [ 39 , 40 , 41 , 42 ].…”

Reporting guideline for overviews of reviews of healthcare interventions: The Preferred Reporting Items for Overviews of Reviews (PRIOR) Explanation & Elaboration

“…Removal of the quasi-experimental study, Gautret et al, 2020, did not alter the results of the pooled analysis (RR 1.02 95%CI 0.91-1.14, I 2 = 0%)." (84) REPORTING BIASES Item 20. Present assessments (collected from systematic reviews and/or assessed anew) of the risk of bias due to missing results in a summary or synthesis (arising from reporting biases at the levels of the systematic reviews, primary studies, and supplemental primary studies, if included) for each summary or synthesis assessed.…”