Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Abstract

Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 p<0.0001). In the sensitivity analysis, the effect on viral clearance disappeared (OR 1.44, 95% CI: 0.87-2.37, p=0.155). The use of HCQ/CQ was associated with a higher risk of mortality (OR 1.26, 95% CI: 1.05-1.51, p<0.0001). Due to huge heterogeneity between the studies (I2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.

The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics

“…For instance, recently, an observational cohort study proposed that HCQ, either alone or in combination with azithromycin, had not a survival advantage among hospitalized patients with COVID-19 [109]. Another meta-analysis also revealed that the administration of HCQ/CQ had not any considerable impacts on SARS-CoV-2 clearance and even increased hospitalized patients with COVID-19 mortality with a higher risk in COVID-19 patients with comorbidities [110]. In a randomized investigation from China, in patients with a mild to moderate SARS-CoV-2 infection recovery rates was not valuable following HCQ therapy [107].…”