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

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, I2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9-1.4, I2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5-4.4, I2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3-5.9, I2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5-59.9, I2 = 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.

Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials.

BACKGROUND: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated. METHODS: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test. RESULTS: Out of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%]. CONCLUSION: There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Perspectives on the Early Quality of Evidence Guiding the Therapeutic Management of SARS-CoV-2: A Systematic Literature Review.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a serious health concern. Repurposing of existing drugs indicated for other conditions seems to be the first choice for immediate therapeutic management. The quality of early evidence favoring the different treatment options needs to be apprised for informed decision-making. METHODS: In this systematic literature review, we apprised the quality of available evidence for different therapeutic options and also the basis for different treatment guidelines. To include all studies that are in different stages of publication, we also included studies from the preprint servers BioRxiv and MedRxiv and published studies from PubMed. RESULTS: We retrieved 5621 articles and included 22 studies for the systematic review. Based on our study, chloroquine/hydroxychloroquine, either alone or in combination with azithromycin, remdesivir, corticosteroids, convalescent sera, ritonavir/lopinavir, tocilizumab and arbidol were evaluated as therapeutic options. The data from different study designs reveal contradictory findings except for convalescent sera for which the evidence available is only from case series. Based on this early evidence, various national guidelines recommend remdesivir, convalescent sera, corticosteroids and hydroxychloroquine in different subsets of patients. CONCLUSION: Establishing consensus with respect to the end points to be assessed for respiratory viruses may enhance the quality of evidence in case of future pandemics. The systematic review highlighted the lacuna and methodologic deficiency in early clinical evidence and included an update on different therapeutic management guidelines. Further clinical evidence from the ongoing trials may lead to evolution of treatment guidelines with the addition of more therapeutic options.