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

Expert Rev Anti Infect Ther. 2022 Feb;20(2):267-278. doi: 10.1080/14787210.2021.1961579. Epub 2021 Aug 17.


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.

Keywords: Antiviral drugs; COVID-19; efficacy; network meta-analysis; randomized controlled trials; safety; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antiviral Agents* / adverse effects
  • Antiviral Agents* / therapeutic use
  • COVID-19 Drug Treatment*
  • Diarrhea / drug therapy
  • Humans
  • Nausea / drug therapy
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic
  • SARS-CoV-2
  • Vomiting / drug therapy


  • Antiviral Agents

Grants and funding

This study was not funded.