Detection of variants with reduced baloxavir marboxil and oseltamivir susceptibility in children with influenza A during the 2019-2020 influenza season

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