Baloxavir marboxil versus oseltamivir for influenza A in children aged 5 years and older: a community-based prospective cohort study

Influenza A places a substantial burden on children. Real-world comparisons of antiviral regimens in community pediatric settings remain limited. This prospective cohort study compared the effectiveness and safety of a single-dose baloxavir marboxil regimen with a standard five-day oseltamivir course in children aged 5 years and older with influenza A, using fever duration as the primary outcome. In this multicenter, prospective, non-randomized observational cohort study, 750 children aged 5–14 years with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed influenza A were enrolled from eight community health centers in Chongqing, China, between October 2024 and December 2025. Treatment assignment was based on guardian preference rather than randomization. The median duration of fever was shorter in the baloxavir group (22.0 h versus 40.5 h; P < 0.001). In exploratory analyses adjusted for multiple comparisons, baloxavir was associated with a shorter median time to viral clearance (24.0 h vs. 72.0 h; false discovery rate [FDR]-adjusted P < 0.001), a lower total complication rate (3.7% vs. 11.2%; FDR-adjusted P = 0.042), more rapid normalization of inflammatory markers and the CD4+/CD8 + ratio, lower revisit rate (2.1% vs. 6.9%; FDR-adjusted P = 0.003), fewer parental work-absence days (2.0 vs. 3.5 days; FDR-adjusted P < 0.001), and fewer adverse drug reactions (6.7% vs. 15.2%; FDR-adjusted P = 0.049). In community-dwelling children with influenza A, baloxavir marboxil was associated with more rapid fever resolution than oseltamivir. Exploratory findings suggested potential benefits regarding viral clearance, complications, healthcare utilization, and tolerability. Because treatment selection was preference-based and open-label, and because influenza A subtype and reduced-susceptibility substitutions were not evaluated, these findings should be interpreted as hypothesis-generating rather than causal. This study was not prospectively registered because it was an observational study. However, the protocol was approved by the relevant ethics committee, and the study was reported following STROBE guidelines for observational research.