Background: We aimed to detect influenza variants with reduced susceptibility to baloxavir marboxil (baloxavir) and oseltamivir and identify differences in the clinical course between children with and without these variants after anti-viral treatment.

Methods: During the 2019-2020 influenza season, we enrolled children with confirmed influenza A (20 treated with baloxavir and 16 with oseltamivir). We analyzed patients´ sequential viral RNA loads and infectious virus titers, the drug susceptibilities of clinical isolates, and amino acid substitutions in the viral polymerase acidic protein subunits or neuraminidase. We assessed patients´ clinical information using questionnaires.

Results: All viral RNA loads and virus titers were significantly decreased after treatment, but we detected baloxavir-resistant and the oseltamivir-resistant variants in 5 of 20 and 3 of 16 patients, respectively. The duration of fever was similar between patients with and without the variants, but infectious viral shedding lasted 3 days longer in patients with baloxavir-resistant variants. In addition, the duration to improvement of clinical symptoms was longer in these patients (75.0 h vs. 29.5 h; p = 0.106).

Conclusions: After anti-viral treatment, the emergence of baloxavir-resistant variants may affect the patients´ clinical course, but oseltamivir-resistant variants had no clinical impact.