In outpatients with COVID-19 during Omicron variant circulation, some antivirals reduce time to recovery

Question: In adult outpatients with symptomatic and confirmed COVID-19 infection, what are the efficacy and safety of antiviral treatments during the period when the Omicron variant of SARS-CoV-2 was prevalent?
Review methods: Searched multiple databases from Nov 2021 (start of Omicron variant circulation) to Sep 2025 for English-language randomized controlled trials (RCTs) that enrolled adults with symptomatic and confirmed diagnosis of COVID-19 in outpatient settings, and compared the benefits and harms of antiviral treatments (including ensitrelvir, favipiravir, lopinavir–ritonavir, molnupiravir, nirmatrelvir–ritonavir, and simnotrelvir–ritonavir) with placebo, usual care, no treatment, a different dose or duration of the same treatment; or other antivirals. Prospective and retrospective cohort (RC) studies with ≥5000 patients and outcome adjustment were included for harms.
Included studies: 6 RCTs and 1 RC study (n = 179 364; mean or median age, 35 to 61 y; 41% to 62% women) met inclusion criteria. All RCTs had some concerns for overall risk of bias (RoB) (Cochrane RoB Tool, 2.0). The RC study had an overall moderate RoB (Risk Of Bias In Non-Randomized Studies—of Interventions tool, Version 2.0).
Bottom line: In outpatients with symptomatic and confirmed COVID-19 during the Omicron variant circulation, some antivirals reduce time to recovery compared with no antivirals.