Safety and Efficacy of Antiviral Drugs for the Treatment of Patients with SARS-CoV-2 Infection: A Systematic Review and Meta-analyses

  1. Zuleika Aponte Torres
  2. Sandra Lopez Leon
  3. Thirumugam Muthuvel
  4. Subha Manivannan
  5. Krutika Srivastava
  6. Marco Pavesi

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Abstract

Objective

To systematically review the safety and efficacy outcomes of using antivirals for the treatment of COVID-19.

Methods

Five databases were screened from inception to 27-Aug-2020. The effects of specific drug interventions on safety and efficacy were assessed in COVID-19 patients. Risk Ratios (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models.

Results

A total of 10 studies were identified which fulfill the inclusion criteria. Patients taking antivirals had 26% less risk of having a severe adverse event (SAE) compared to controls (RR, 0.74, CI:0.62 to 0.89, P=0.002). Clinical improvement at day 14 was observed among the cases treated with antivirals compared to the control group (RR 1.24, CI: 1.00 to 1.53 p=0.05).

Conclusion

There is evidence that Remdesivir and LPV/r reduces the hospital length of stay and that patients to which antivirals were administered had less SAE and improvement when compared to patients not prescribed with antivirals. Due to a lack of power and the quality of the studies, it was not possible to determine which antivirals have a greater risk-benefit balance, and therefore the optimal approach to antiviral treatment is still uncertain.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.03.20187526: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The literature search was conducted in PubMed, EMBASE, Medrxiv, Cochrane Central Register of Controlled Trials (CENTRAL), and LitCOVID databases from inception to 27-Aug-2020 to find articles providing information on the efficacy and safety of antiviral drugs in patients with SARS-CoV-2.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Since all of the studies included in the meta-analyses had different types of limitations, it is important to focus on the systematic review and evaluate single studies with high quality. The study by Wang et al. was the only study with high quality. It was the first placebo-controlled, double-blinded RCT. Even though the study was conducted in ten hospitals, the study ended prematurely after including 237 patients due to slow recruitment, which meant the trial was underpowered and the outcome was inconclusive. The study showed that patients treated with Remdesivir within 10 days after the onset of clinical symptoms had a reduction of time on mechanical ventilation and a faster clinical improvement (2 days shorter) compared to standard therapy. In addition, the study by Beigel et al showed that Remdesivir shortened the time to recovery in hospitalized patients with COVID-19 (Beigel et al., 2020). Further clinical trial is warranted to clarify and strengthen the effect of Remdesivir on COVID-19 patients. Concerning the results of LPV/r, it is important to note that the studies presented major limitations including the risk of bias and lack of power, therefore high quality is needed before a conclusion can be made. In vitro studies showed that LPC/r had antiviral activity against SARS-CoV (Choy et al., 2020; Li and De Clercq, 2020). In addition, the results of clinical studies reported that patients treated with LPV/r had a reduction in intubation rate and mortality with Lopina...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.09.03.20187526v1 on medRxiv