Effect of various treatment modalities on the novel coronavirus (nCOV-2019) infection in humans: a systematic review & meta-analysis

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Abstract

Background and aim

Several therapeutic agents have been investigated for the treatment of novel Coronavirus-2019 (nCOV-2019). We aimed to conduct a systematic review and meta-analysis to assess the effect of various treatment modalities in nCOV-2019 patients.

Methods

An extensive literature search was conducted before 22 May 2020 in PubMed, Google Scholar, Cochrane library databases. Quality assessment was performed using Newcastle Ottawa Scale. A fixed-effect model was applied if I 2 <50%, else the results were combined using random-effect model. Risk Ratio (RR) or Standardized Mean Difference (SMD) along-with 95% Confidence Interval (95%CI) were used to pool the results. Between study heterogeneity was explored using influence and sensitivity analyses & publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.

Results

Eighty-one studies involving 44 in vitro and 37 clinical studies including 8662 nCOV-2019 patients were included in the review. Lopinavir-Ritonavir compared to controls was significantly associated with shorter mean time to clinical improvement (SMD -0.32; 95%CI -0.57 to -0.06) and Remdesivir compared to placebo was significantly associated with better overall clinical improvement (RR 1.17; 95%CI 1.07 to 1.29). Hydroxychloroquine was associated with less overall clinical improvement (RR 0.88; 95%CI 0.79 to 0.98) and longer time to clinical improvement (SMD 0.64; 95%CI 0.33 to 0.94), It additionally had higher all-cause mortality (RR 1.6; 95%CI 1.26 to 2.03) and more total adverse events (RR 1.84; 95% CI 1.58 to 2.13).

Conclusion

Our meta-analysis suggests that except in vitro studies, no treatment till now has shown clear-cut benefit on nCOV-2019 patients. Lopinavir-Ritonavir and Remdesivir have shown some benefits in terms less time to clinical improvement and better overall clinical improvement. Hydroxychloroquine use has a risk of higher mortality and adverse events. Results from upcoming large clinical trials must be awaited to draw any profound conclusions.

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