A Systematic Review and Meta-analysis of Therapeutic options against SARS-CoV-2

ABSTRACT

ImportanceTreatment options for Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on the efficacy and safety profiles. ObjectiveTo assess if the effect estimate of any intervention improves the outcomes and safety profile. Data sourcesPubMed, Embase, Cochrane Central were searched from December 1, 2019 to May 11, 2020. Study selectionAny prospective/retrospective clinical study on SARS-CoV-2 patients [≥]18 years of age with report on therapeutic interventions. Data synthesis and extractionData was screened and extracted by two independent investigators. Main outcomes and measuresThe primary outcome was all-cause in-hospital mortality. The secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, progression to severe disease, median time for clinical recovery and anti-viral clearance. Pooled rates and odds ratios (OR) were calculated. ResultsA total of 29 studies with 5207 participants were included in the analysis. The pooled all-cause in-hospital mortality rate was 12.8% (95%CI 8.1%-17.4%) in intervention arm. There was no significant difference in mortality between both arms overall (OR 1.36, 95% CI 0.97-1.89). The mortality was significantly higher in the Hydroxychloroquine (HCQ) group compared to control (1.86, 95% CI 1.38 - 2.50). The need for mechanical ventilation in patients with mild-moderate disease was 13.5% vs 9.8% in intervention and control groups, with no significant difference (OR 1.58, 95% CI 0.60 - 4.15).The median duration for viral clearance in the intervention arm was 6.1 (IQR 4.3 - 8.8) days and control arm was 9 (IQR 4.5 - 14) days, with no significant difference between the groups (p = 0.37). There was no significant difference between pooled adverse event rates in intervention and control groups 34% vs 29.5% (OR 1.44, 95% CI 0.70 - 2.94), respectively. However, incidence of adverse events was significantly higher in HCQ sub-group (OR 3.88, 95% CI 1.60 - 9.45, I2 = 0%). There was no significant difference in other secondary outcomes. Conclusion and relevanceThe use of hydroxychloroquine was associated with increased mortality and adverse event rates. No other therapeutic intervention including Lopinavir/Ritonavir, Remdesivir or Tocilizumab seem to alter the natural course of the disease. There is a further need for well-designed randomized clinical trials. Article summary lineThe use of hydroxychloroquine was associated with increased mortality and adverse event rates in Severe acute respiratory syndrome-related coronavirus-2 infection and other therapeutic interventions did not show any difference in outcomes: