Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis.

BACKGROUND: To better inform clinical practice, we summarized the findings from randomized controlled trials (RCTs) of antivirals for COVID-19. METHODS: We systematically searched for literature up to September 2020, and included English-language publications of RCTs among hospitalized COVID-19 patients. We conducted network meta-analysis combining results of both the direct and indirect comparisons of interventions. The efficacy outcomes were clinical progression, all-cause mortality, and viral clearance, and safety outcomes were diarrhea, nausea, and vomiting. We generated treatment rankings (best to worst) and summarized rank probabilities using rankogram. RESULTS: We included 15 RCTs (14,418 patients) from 7,237 retrieved citations. There was no evidence for efficacy of the assessed antivirals compared with placebo/no treatment or with another antiviral for all efficacy outcomes. Lopinavir (400 mg)/ritonavir (100 mg) significantly increased diarrhea, nausea, and vomiting compared with placebo/no treatment and other antivirals, and was ranked worst for these outcomes, while triazavirin (250 mg), baloxavir marboxil (80 mg), and remdesivir (100 mg - 10 days) ranked best, respectively. CONCLUSIONS AND RELEVANCE: The available evidence does not support the use of any antiviral drugs for COVID-19. Cautious interpretations of the findings are, however, advised considering the paucity of the evidence. More RCTs are needed for a stronger evidence base.

Remdesivir for coronavirus disease 2019 (COVID-19): a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: In view of many unanswered clinical questions regarding treatment of COVID-19 with remdesivir, we systematically identified, critically appraised and summarized the findings from randomized controlled trials (RCTs) of remdesivir for COVID-19. METHODS: We searched relevant databases/websites (up to September 2020) and selected English-language RCT publications of remdesivir for COVID-19. We conducted meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA) for the efficacy outcomes: all-cause mortality, viral burden and clinical progression. Safety outcomes were diarrhoea, nausea, and vomiting. We calculated the relative risk (RR) and 95% confidence interval (CI) for all outcomes. Statistical heterogeneity was calculated using the I2 statistic. RESULTS: We included five RCTs (7540 participants) from 7237 citations. Most (80%) were of an unclear to high risk of bias. There was no evidence of a significant improvement with remdesivir (100 mg, 10 days) regarding all-cause mortality (RR 0.94, CI 0.82-1.07; I2 = 0%; 4 RCTs; 7143 patients), clinical progression (RR 1.08, CI 0.99-1.18; I2 = 70.4%; 3 RCTs; 1692 patients), or diarrhoea (RR 0.82, CI 0.40-1.66; I2 = 0%; 2 RCTs; 630 patients). Nausea occurred more often with remdesivir (RR 2.77, CI 1.28-6.03; I2 = 0%; 2 RCTs; 630 patients). TSA showed that the required information size was not reached for firm conclusions to be drawn. CONCLUSIONS AND RELEVANCE: There is insufficient evidence to support the use of remdesivir for treatment of COVID-19. More high-quality RCTs are needed for a stronger evidence. Until then, remdesivir should remain an experimental drug for COVID-19.