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Ribavirin for Treatment of Subjects with Respiratory Syncytial Virus-Related Infection: A Systematic Review and Meta-Analysis

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Abstract

Introduction

Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower respiratory tract infections (LRTIs) in all age groups, adults with comorbidities, and immunocompromised patients. The aim was to summarize the evidence concerning efficacy and safety of ribavirin in subjects diagnosed with RSV associated with LRTI.

Methods

A systematic review and meta-analysis were performed. Eligible studies were observational (> 10 subjects) and randomized-controlled trials of subjects with aerosol/oral ribavirin for RSV-LRTI. Comparator was supportive care or placebo. Systematic search on PubMed, Cochrane Library, and Web of Science databases was conducted between January 2001 and January 2022. PROSPERO register number: CRD42022308147.

Results

After retrieving 907 studies, 10 observational studies and 1 randomized controlled trial were included (4/11 high quality of evidence). Seven studies included subjects with haematological malignancy/stem cell transplant, two lung transplants, and two healthy individuals. A total of 788 subjects diagnosed with RSV infection were included; 14.3% of them presented with only LRTI. Among 445 subjects treated with ribavirin, 195 (43.8%) received an aerosolized formulation. Pooled meta-analysis showed no differences in mortality [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.28–1.42] in all subjects treated with aerosol/oral ribavirin compared to supportive care. In subgroup analysis, mortality was significantly lower in haematological subjects (RR: 0.32; 95% CI: 0.14–0.71), but did not differ significantly in lung transplant recipients (RR: 0.89; 95% CI 0.31–2.56). Oral ribavirin (vs. supportive care) was associated with increased viral clearance (RR: 2.60; 95% CI: 1.35–4.99). Seventeen adverse events were reported among 119 subjects, but none were severe.

Conclusion

Ribavirin should be considered for treatment of RSV-LRTI in haematological subjects. There is a lack of evidence to support its use in lung transplant recipients. Oral formulation appears to be an easier, safe, and cost-effective alternative to aerosolized ribavirin. Further advances needs to focus on newer antivirals.

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Acknowledgements

Funding

This work was funded by CIBERES, Instituto de Salud Carlos III, Madrid, Spain (Fondos FEDER: CB06-06–036). No funding or sponsorship was received for the publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Sofia Tejada: Methodology, Software, Formal analysis, Writing-original draft. Raquel Martinez-Reviejo: Methodology, Validation. Hanife N. Karakoc: Methodology. Yolanda Peña-López: Writing-original draft, Writing—Review & Editing. Oriol Manuel: Conceptualization, Writing—Review & Editing. Jordi Rello: Conceptualization, Writing—Review & Editing, Supervision. All authors read and approved the final manuscript.

Disclosures

Sofia Tejada, Raquel Martinez-Reviejo, Hanife N. Karakoc, Yolanda Peña-López, Oriol Manuel, and Jordi Rello declare that they have no competing interests. This study was part of the doctoral thesis from Sofia Tejada at the Medicine Department, University of Barcelona, Spain.

Compliance with Ethics Guidelines

Ethics committee approval is not applicable. The present article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

Data Availability

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

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Authors and Affiliations

  1. Centro de Investigación Biomédica En Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Sofia Tejada, Raquel Martinez-Reviejo & Jordi Rello

  2. Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d’Hebron Institut of Research (VHIR), Ps Vall d’Hebron 119 AMI-14th Floor, 08035, Barcelona, Spain

    Sofia Tejada, Raquel Martinez-Reviejo, Yolanda Peña-López & Jordi Rello

  3. Karadeniz Technical University School of Medicine, Trabzon, Turkey

    Hanife N. Karakoc

  4. Paediatric Critical Care Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Yolanda Peña-López

  5. Service of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland

    Oriol Manuel

  6. Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland

    Oriol Manuel

  7. Clinical Research, CHU Nimes, Universite de Nimes-Montpellier, Nîmes, France

    Jordi Rello

  8. Medicine Department, Universitat Internacional de Catalunya (UIC), Barcelona, Spain

    Jordi Rello

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  1. Sofia Tejada
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  4. Yolanda Peña-López
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Corresponding author

Correspondence to Sofia Tejada.

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Tejada, S., Martinez-Reviejo, R., Karakoc, H.N. et al. Ribavirin for Treatment of Subjects with Respiratory Syncytial Virus-Related Infection: A Systematic Review and Meta-Analysis. Adv Ther 39, 4037–4051 (2022). https://doi.org/10.1007/s12325-022-02256-5

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