Impact of some antiviral drugs on health care utilization for patients with COVID-19: a systematic review and meta-analysis

ABSTRACT

Background

We aimed to assess the impact of antiviral drugs (fluvoxamine,remdesivir, lopinavir/ritonavir (LPV/r), molnupiravir, andnirmatrelvir/ritonavir (NRV/r)) on health care utilization (HCU) inCOVID-19 patients. We summarized findings from randomized controlledtrials (RCTs) and observational studies.

Methods

We systematically searched four medical databases (PubMed, Web of Science, Embase, Cochrane Library) for COVID-19 studies up to February 15, 2023. A comprehensive review, meta-analysis, sensitivity analysis, and subgroup analysis were conducted. Pooled effects with 95% confidence intervals (CIs) were calculated for antiviral drugs' impact on hospitalization, mechanical ventilation (MV), and intensive care unit (ICU) outcomes.

Results

Our analysis included 34 studies (584,978 patients). Meta-analysisindicated potential benefits: remdesivir and molnupiravir potentiallyreduced MV risk, and NRV/r correlated with lower hospitalizationrates. However, LPV/r did not notably curb HCU. Remdesivir waspreferable for high-risk COVID-19 patients, while molnupiravir andNRV/r were recommended for those aged 60 and above.

Conclusion

Remdesivir, molnupiravir, and NRV/r may reduce HCU during the COVID-19 pandemic. However, due to limited study details and significant heterogeneity in effect estimates, further precise evidence is crucial, especially concerning emerging variants.

KEYWORDS:

• Antiviral drug
• coronavirus disease 2019
• health care utilization
• meta-analysis
• systematic review

Article highlights

• Antiviral drugs against COVID-19- the impact on health care utilization, particularly with respect to hospitalization, mechanical ventilation, and ICU admission were investigated. These findings are crucial in assessing drug efficacy for approval and guiding clinical practice.

• This systematic review and meta-analysis included thirty-four studies comprising of 15 randomized controlled trials (RCTs) and 19 observational studies involving a total of 584,978 patients.

• Molnupiravir and nirmatrelvir/ritonavir, oral antiviral drugs were both found to be a particularly beneficial home-treatment for COVID-19 in the population aged 60 years and above.

• Remdesivir, as an intravenous medication, was more suitable for high-risk patients requiring oxygen support.

• High heterogeneity was observed in the overall effects across most of the meta-analyses.

• Further high-quality research is necessary to validate findings and provide stronger evidence to support drug approval and guide clinical practice.

Abbreviations

Coronavirus disease 2019 (COVID-19); health care utilization (HCU); lopinavir/ritonavir (LPV/r); nirmatrelvir/ritonavir (NRV/r); mechanical ventilation (MV); intensive care unit (ICU); severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); World Health Organization (WHO); human immunodeficiency virus (HIV); PF-07321332 (nirmatrelvir); main protease (Mpro); Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA); randomized controlled trials (RCTs); Cochrane risk-of-bias tool version 2 (RoB 2); Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I); odds ratios (OR); risk ratios (RR); hazard ratios (HR); confidence intervals (CI); Centers for Disease Control and Prevention (CDC); 3Rs (OR, RR, and HR); RdRp (RNA-dependent RNA polymerase); Food and Drug Administration (FDA); National Medical Products Administration (NMPA).

Acknowledgments

We thank all the authors of the included papers.

Declaration of interest statement

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.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethical approval

We received an ethics exemption for this systematic review and meta-analysis since the data utilized were publicly accessible.

Author contributions

#Bincai Wei and Ruhao Zhang participated in the study conception and design and extracted data. Bincai Wei performed the data analyses. Ruhao Zhang checked the statistical consistency. Bincai Wei contributed to data interpretation and drafted the manuscript. Junyao Zheng, Huatang Zeng, Liqun Wu, Rongxin He, Hao Xue, Jinlin Liu, and Bin Zhu critically reviewed the manuscript. Bincai Wei and Ruhao Zhang contributed to the discussion, are guarantors of this work, have full access to all the data in the study, and take responsibility for the integrity and accuracy of the data analysis. All authors approved the final version of the manuscript.

SUPPLEMENTARY MATERIAL

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2023.2254491

Additional information

Funding

This paper was funded by the Shenzhen Science and Technology Program [Grant No.: JCYJ20220530113208019], the Guangdong Basic and Applied Basic Research Fund Project (Regional Joint Fund-Youth Fund Project) [grant number: 2019A1515110583], and the Shenzhen Philosophy and Social Science Program [grant number: SZ2023C007].