Antiviral Benefit Uncertain in Vaccinated Omicron-Era COVID-19 Patients

This systematic review reframes nirmatrelvir-ritonavir and molnupiravir effectiveness for stewardship in vaccinated Omicron-era populations, exposing a stark gap between observational benefit signals and negative or underpowered randomized data.

nirmatrelvir-ritonavirmolnupiravirPaxlovidLagevriooral antiviralsCOVID-19SARS-CoV-2Omicronsystematic reviewmeta-analysisantimicrobial stewardshipvaccinated populations Infectious Disease / Antimicrobials

Background Information

Nirmatrelvir-ritonavir may reduce hospitalization in vaccinated patients.

Understanding antiviral effectiveness in vaccinated individuals during the Omicron era is crucial for optimizing treatment strategies. Nirmatrelvir-ritonavir showed a reduction in hospitalization and mortality in observational studies, while molnupiravir did not demonstrate significant benefits. RCTs did not show benefits in vaccinated populations, but observational studies suggest nirmatrelvir-ritonavir may reduce severe outcomes. Nirmatrelvir-ritonavir may offer benefits in vaccinated patients, while molnupiravir's effectiveness remains uncertain.

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Authors: Edwards LJ, Liu B, Wood JG, Stephens N, Cheng AC

Citation: Edwards LJ, Liu B, Wood JG, et al. Evaluating the Effectiveness of Antivirals for COVID-19 in the Post-vaccine, Omicron Era: A Systematic Review and Meta-analysis. Open forum infectious diseases. 2026;13(7):ofag339. doi:10.1093/ofid/ofag339

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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