Effectiveness of nirmatrelvir-ritonavir for the treatment of patients with mild to moderate COVID-19 and at high risk of hospitalization: Systematic review and meta-analyses of observational studies

PLoS One. 2023 Oct 12;18(10):e0284006. doi: 10.1371/journal.pone.0284006. eCollection 2023.

Abstract

Objective: To assess the effectiveness of nirmatrelvir-ritonavir in the treatment of outpatients with mild to moderate COVID-19 who are at higher risk of developing severe illness, through a systematic review with meta-analyses of observational studies.

Methods: A systematic search was performed, in accordance with the Cochrane search methods, to identify observational studies that met the inclusion criteria. The outcomes of mortality and hospitalization were analyzed. Search was conducted on PubMed, EMBASE, and The Cochrane Library. Two reviewers independently screened references, selected the studies, extracted the data, assessed the risk of bias using ROBINS-I tool and evaluated the quality of evidence using the GRADE tool. This study followed the PRISMA reporting guideline.

Results: A total of 16 observational studies were finally included. The results of the meta-analysis showed that in comparison to standard treatment without antivirals, nirmatrelvir-ritonavir reduced the risk of death by 59% (OR = 0.41; 95% CI: 0.35-0.52; moderate certainty of evidence). In addition, a 53% reduction in the risk of hospital admission was observed (OR = 0.47; 95% CI: 0.36-0.60, with very low certainty of evidence). For the composite outcome of hospitalization and/or mortality, there was a 56% risk reduction (OR = 0.44; 95% CI: 0.31-0.64, moderate certainty of evidence).

Conclusion: The results suggest that nirmatrelvir-ritonavir could be effective in reducing mortality and hospitalization. The results were valid in vaccinated or unvaccinated high-risk individuals with COVID-19. Data from ongoing and future trials may further advance our understanding of the effectiveness and safety of nirmatrelvir-ritonavir and help improve treatment guidelines for COVID-19.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 Drug Treatment
  • COVID-19*
  • Hospitalization
  • Humans
  • Ritonavir / therapeutic use

Substances

  • nirmatrelvir
  • Ritonavir

Grants and funding

This study was funded by the grant ‘Working together to fight antimicrobial resistance’, internal number 049126, EUC agreement PI/2019/406-773; as well as by the partnership between the Government of Canada and the Pan American Health Organization (PAHO/WHO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.