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

ABSTRACT

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
• randomized controlled trials
• efficacy
• safety
• systematic review
• network meta-analysis

Article highlights

• We systematically identified, critically appraised, and summarized the findings from randomized controlled trials (RCTs) of antiviral drugs for the treatment of COVID-19.

• This review included 15 RCTs involving 14,418 hospitalized COVID-19 patients.

• Most of the RCTs (80%) were of an unclear to high risk of bias.

• There was no evidence for efficacy of any of the assessed antiviral drugs for improving clinical progression, reducing all-cause mortality and viral clearance among the patients.

• Lopinavir (400 mg) with ritonavir (100 mg) significantly increased diarrhea, nausea, and vomiting compared with placebo/no treatment and other antiviral drugs.

• Triazavirin (250 mg), baloxavir marboxil (80 mg), and remdesivir (100 mg – 10 days) ranked best with regard to diarrhea, nausea, and vomiting, respectively.

Supplementary material

Supplemental data for this article can be accessed here.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was not funded.