Table 1.

Characteristics of selected articles for systematic review in “A third force in Management of COVID-19”.

S/No	Categories	Authors	Purpose	Samples	Key findings	Level of Evidence
1	Randomised Clinical Trials (RCT)	Spinner et al. (9)	To determine the efficacy of 5 or 10 days of Remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.	USA, Europe & Asia	N = 586/596 (numerator-completed; Denominator-Started) Remdesivir demonstrated strong clinical benefit in a placebo-controlled trial in patients with severe COVID-19 with efficacy best on days 5 and 10; but its effect on moderate disease is not known. Clinical status on day 11, was not significantly different from day 5 and 10 ((P = 0.18 by Wilcoxon rank sum test).	2
2	Randomised Control Trials	Beigel et al. (12)	To assess the efficacy of Remdesivir on SARS-COV-2 infections.	USA, UK, Germany, Spain, Denmark, Japan, Korea, Mexico and Singapore	N = 1062 Those who received Remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) observed among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P < 0.001, by a log-rank test). Remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.	2
3	Randomised Controlled Trials	Wang et al. (13)	To analyse the efficacy of Remdesivir on COVID-19.	China	N = 237 RCT involving 237 patients (158 to Remdesivir and 79 to placebo) revealed no difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although, not statistically significant, the patients that received Remdesivir had a numerically faster time to clinical improvement than those that received placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43])	2
4	Randomised Control Trial	Goldman et al. (14)	To assess the efficacy of Remdesivir on COVID-19	USA, UK, Germany, Spain, Denmark, Japan, Korea, Mexico and Singapore	N = 397 The patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group.In patients with severe Covid-19 not requiring mechanical ventilation, the trial did not show a significant difference between a 5-day course and a 10-day course of Remdesivir.
5	Randomised Control Trials	Grein et al. (15)	To investigate efficacy of Remdesivir in compassionate use on patients	United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.	N = 53/61The patients whose data were analysed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were on mechanical ventilation and 4 (8%) were on extracorporeal membrane oxygenation.At median follow-up of 18 days, 36 (68%) improved on oxygen-support, including the extubated 17 of 30 patients (57%) on mechanical ventilator. Twenty-five patients (47%) got discharged, 7 (13%) died. Overall mortality was 18% (6 of 34) of those on active ventilation and 5% (1 of 19) of those not on ventilation.	2
6	Systematic Review	Rochwerg et al. (16)	To provide clinical guide on management of Severe COVID-19 with Remdesivir.	Global	N = 13000 The study was based on the RCTT1 trial on Remdesivir. The guideline panel makes a weak recommendation for the use of Remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining Remdesivir.	1
7	Systematic Review	Piscoya et al. (17)	To investigate the efficacy and safety of Remdesivir for the treatment of COVID-19	Global	N = 22960 Four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous Remdesivir 200 mg the first day and 100 mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs (Adverse effects); the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with Remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95% CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care	1
8	Systematic Review	Yokoyama et al.(18)	To compare the rate of clinical improvement among patients with COVID-19 that received 5-day course of Remdesivir with 10-day course and standard care	Global	The meta-analysis of 4 RCTs showed a significant clinical improvement higher in the 5-day Remdesivir group and 10-day Remdesivir group compared to standard care group (OR [95% confidence interval [CI]] = 1.89 [1.40–2.56], P < 0.001, OR [95% CI] = 1.38 [1.15–1.66], P < 0.001, respectively). Clinical improvement was significantly higher in the 5-day Remdesivir group compared to the 10-day Remdesivir group (OR [95% confidence interval [CI]] = 1.37 [1.01–1.85], P = 0.041). Therefore, the use of Remdesivir for COVID-19 treatment was associated with the significantly higher clinical improvement rate compared with standard care alone.	1
9	Systematic review	Verdugo-Paiva et al.(19)	To assess the role of Remdesivir in the treatment of patients with COVID-19	Israel, Iran, China, Japan, Korea, Australia, New-zealand, Brazil, Lebanon, Pan-Africa, Netgerlands, Srilanka, India, Germany	N=Not AvailableEffect of Remdesivir on mortality is uncertain (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and relevance of invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). Remdesivir appears associated with increase in adverse effects on COVID-19 patients (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence).	1
10	Systematic review	Nasir et al.(20)	To assess the evidence for efficacy and safety in the compassionate use of Remdesivir in severeCOVID-19 as re-purposeful use.	China, USA. UK and KSA	N = 523 Seven articles were reviewed in the current systematic review.The safety and efficacy of Remdesivir in COVID-19 cases requires high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.	1
11	Systematic review	Alegre-Del et al.(21)	To analyse the reliability and clinical applicability of subgroup findings on the effect of Remdesivir on mortality in patients with COVID-19	Global	N = 53/61 A validated tool was used to assess the findings of subgroup analyses in randomized clinical trials, including meta-analysis annexed to the SOLIDARITY study. This study suggests too much uncertainty in the hypothesis that Remdesivir could reduce mortality in patients with severe COVID-19 who require non-high flow oxygen. It elucidated that it might be a chance finding. More Randomised studies were recommended.	1