DOI: 10.1002/jmv.28889 ISSN: 0146-6615

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

Bahman Amani, Arash Akbarzadeh, Behnam Amani, Rouhollah Shabestan, Saeed Khorramnia, Zia Navidi, Kourosh Rajabkhah, Vida Kardanmoghadam
  • Infectious Diseases
  • Virology


This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 (COVID‐19). To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta‐Analysis software. Eighteen studies involving 57 659 patients were included in the meta‐analysis. The meta‐analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all‐cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44–0.67), all‐cause hospitalization rate (OR = 0.61, 95% CI: 0.54–0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38–0.99), and negative polymerase chain reaction conversion time (mean difference = −1.55, 95% CI: −1.74 to −1.37). However, no significant difference was observed between the two groups in terms of COVID‐19 rebound (OR = 0.87, 95% CI: 0.71–1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI: 1.57–4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69–2.00). The present meta‐analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID‐19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

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