Randomized placebo-controlled trials of remdesivir in severe COVID-19 patients: A Systematic Review and Meta-analysis

Sarfraz, A.; Sarfraz, Z.; Sanchez-Gonalez, M. A.; Michel, J.; Michel, G.; Frontela, O.; Posada, J.; Cardona, J.; Angueira, E.

Background: The first cases of the coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. No antiviral treatment options are currently available with proven clinical efficacy. However, preliminary findings from phase III trials suggest that remdesivir is an effective and safe treatment option for COVID-19 patients with severe disease. Objective: The aim of the present meta-analysis is to investigate whether remdesivir is effective for treating COVID-19 including reduced in-hospital adverse events, oxygen support, and mortality rates. Methods: Using PRISMA reporting guidelines, a review was conducted from January 1 2020 until 6 August 2020 with MeSH terms including COVID-19, coronavirus, SARS-CoV-2, COVID, remdesivir, adenosine nucleoside triphosphate analog, Veklury using Medline, Scopus, and CINAHL Plus. A modified Delphi process was used to include the studies and ensure that the objectives were addressed (Appendix A). Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel Haenszel (M-H) random-effects method in Review Manager 5.4. Results: Randomized controlled trials pooled in 2,429 participants with 41.6% (n=1011) in the remdesivir group and 58.4% (n=1,418) in the placebo group. The placebo group had a higher risk of mortality as compared to the intervention group with significant odds ratio (OR=0.61) (95% confidence interval of 0.45-0.83; P=0.001). There was moderate heterogeneity among the studies. Conclusions: Our findings suggest that remdesivir extends clinical benefits by reducing mortality, adverse events and oxygen support in moderate to severely ill COVID-19 patients. Concerted efforts and further randomized placebo-controlled trials are warranted to examine the potency of anti-viral drugs and immune-pathological host responses contributing to severity of COVID-19.