The efficacy of remdesivir in coronavirus disease 2019 (COVID-19): a systematic review

Abstract

Background and Objectives: Researchers all around the world are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the efficacy and safety of treatment with Remdesivir in hospitalized patients with COVID-19. Materials and Methods: We performed a systematic search in Pubmed, Embase, Web of Science, Google scholar and MedRxiv for relevant observational and interventional studies. The outcomes measures were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: Three randomized controlled trials and 2 cohort studies were included in our study. In the 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day efficacy of treatment with Remdesivir versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that the efficacy of Remdesivir was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowered 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have a significant difference; however, severe adverse event rate was lower in the 5-day Remdesivir group compared to the 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe, and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.

Most published systematic reviews of remdesivir for COVID-19 were redundant and lacked currency

“…We included 36 reviews of remdesivir [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] plus two major living reviews of all treatments for COVID-19 [ 25 , 26 ] (collectively reported in 45 publications up to May 20, 2021). The first review was published on April 30, 2020 [42] , the day after the first randomized trial of remdesivir and the preliminary findings of two other trials were published.…”

“…Nine were first published as preprints. Of these, three were subsequently published without any changes to the search date or studies included (shown as single reviews in Figure 1 ) [ 54 , 55 , 60 ], and one was updated with a new search and additional studies (shown as separate reviews in Figure 1 ) [ 49 , 50 ].

Figure 1 Timeline and currency of randomized trials and systematic reviews of remdesivir for COVID-19 [NB.

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Potential limitations in systematic review studies assessing the effect of the main intervention for treatment/therapy of COVID-19 patients: An overview

“…Heterogeneity across the studies may affect the study results ( 65 ). For instance, pooling the data of the original articles would be highly difficult due to heterogeneity in the study design and reported outcomes ( 25 ), and heterogeneity in disease severity could affect the treatment output.…”

Drug-Induced Liver Disturbance During the Treatment of COVID-19

“…The authors concluded that liver disturbance was rare in both groups, and that there was no statistical difference between the two groups. Thus, considering the duration of treatment and comparison with the placebo, we believe that the association between remdesivir and liver injury in patients with COVID-19 was weak (Roshanshad et al, 2020).…”