Early Antiviral Therapy Cuts Influenza Hospitalization Risk Children

Children who received antiviral therapy within 48 hours of influenza symptom onset had an 81% lower risk of subsequent hospitalization compared with those treated later or not at all, according to a multicenter, age- and season-matched, retrospective case-control study published in Pediatrics.¹

The study followed 1492 children with laboratory-confirmed influenza who sought care at hospitals in northern Taiwan between January 2020 and October 2023, and it is among the first to directly link early antiviral initiation to reduced hospitalization risk in a pediatric outpatient population, rather than relying on symptom-duration end points alone.

Study Design and Key Findings

The study matched 354 children who were later hospitalized or died because of influenza (cases) to 1138 nonhospitalized children (controls) by the timing of their initial visit and age strata. Participants had a mean age of 7.1 years (SD, 4.6), and 86.7% were infected with influenza A. Early antiviral therapy was defined as treatment initiated within 48 hours of symptom onset, consistent with World Health Organization and Infectious Diseases Society of America (IDSA) guidance.¹

Among the 1492 children, 1206 (80.8%) received early antiviral therapy, 269 (18.0%) received late therapy (more than 48 hours after symptom onset), and 17 (1.1%) received no antiviral treatment. Children who received early therapy had markedly lower rates of hospitalization (16.1% [194 of 1206] vs 55.9% [160 of 286]; P < .001) and influenza-related severe illness (0.7% [9 of 1206] vs 3.1% [9 of 286]; P < .01) compared with those who received late or no treatment.¹

After adjustment for covariates including pediatric comorbidity index, early antibiotic and corticosteroid use, co-infections, and influenza vaccination status, early antiviral therapy was associated with an 81% lower risk of hospitalization (adjusted odds ratio [aOR], 0.19; 95% CI, 0.14-0.27). No deaths occurred among study participants.¹

Protective Effect Held Across Age Groups and Sensitivity Analyses

The benefit of early treatment was consistent regardless of age. Among children 5 years or younger, early antiviral therapy was associated with an 81% reduction in hospitalization risk (aOR, 0.19; 95% CI, 0.12-0.31), and among children older than 5 years, the reduction was 85% (aOR, 0.15; 95% CI, 0.09-0.25). The finding remained robust across sensitivity analyses comparing early versus late antiviral initiation, excluding patients treated with intravenous peramivir, and excluding the COVID-19 pandemic period, with the estimated protective effect ranging from 80% to 82%.¹

E-values for the main analysis reached as high as 10.0, ranging from 9.47 to 19.49 across subgroups, indicating that an extremely strong unmeasured confounder would be needed to fully explain the observed association. Subgroup analyses comparing oral oseltamivir (Tamiflu) with inhaled zanamivir (Relenza) showed consistent results across both agents.¹

Other factors independently associated with an increased risk of influenza-related hospitalization included younger age, a higher pediatric comorbidity index, early antibiotic use, and coinfection with another virus or bacterial pathogen. Influenza vaccination in the preceding year was independently protective (aOR, 0.62; 95% CI, 0.42-0.90).¹

"Early antiviral therapy in pediatric outpatients with influenza substantially reduces the risk of subsequent severe illness and hospitalization, supporting prompt initiation of treatment in this population," the study authors wrote in Pediatrics, cautioning that early treatment should supplement, not replace, vaccination, particularly for infants younger than 6 months who are not yet eligible for the flu vaccine.¹

A Persistent Gap in Guideline-Concordant Treatment

The Taiwan findings arrive alongside earlier evidence that antiviral therapy is inconsistently prescribed to children who meet criteria for it. A cross-sectional study of 274,213 Medicaid-enrolled children aged 1 to 18 years at high risk for influenza complications found that only 159,350 (58.1%) received antiviral treatment within 2 days of diagnosis, meaning 42% did not receive guideline-concordant care despite recommendations from the American Academy of Pediatrics (AAP), IDSA, and the CDC that high-risk children receive antiviral treatment regardless of symptom duration.²

That study found antiviral treatment was more likely among children with asthma (aOR, 1.13; 95% CI, 1.11-1.16), immunosuppression (aOR, 1.10; 95% CI, 1.05-1.16), or other complex chronic conditions (aOR, 1.04; 95% CI, 1.01-1.07) and among those seen in urgent care settings (aOR, 1.3; 95% CI, 1.26-1.34). Treatment was less likely among children aged 2 to 5 years compared with those aged 6 to 17 years (aOR, 0.95; 95% CI, 0.93-0.97), those residing in a nursing home or other chronic care facility (aOR, 0.61; 95% CI, 0.46-0.81), and those evaluated in an emergency department (aOR, 0.66; 95% CI, 0.63-0.71).²

The study's authors noted that pharmacy closures and symptom improvement before a caregiver could pick up a prescription may account for some of the gap between prescribing and dispensing.²

Implications for Pharmacists

For pharmacists, the Taiwan findings sharpen the case for urgency once a child presents with flu-like symptoms. The CDC currently recommends 4 FDA-approved antivirals: oseltamivir (approved for children as young as 14 days); inhaled zanamivir (approved for ages 7 years and older and generally avoided in children with asthma or chronic lung disease); intravenous peramivir (Rapivab, approved for ages 6 months and older); and baloxavir marboxil (Xofluza, approved for children aged 5 to 11 years without chronic conditions and for all children aged 12 years and older).^3,4

All are most effective when started within 2 days of symptom onset, though the CDC notes that children who present later, particularly those at high risk, can still benefit from treatment.^3,4 Neuraminidase inhibitors work by blocking the viral neuraminidase enzyme needed for new virus particles to be released from infected cells, a process tied to peak viral replication in the respiratory tract 24 to 72 hours after infection, which underlies the emphasis on early dosing.⁵

Community and health-system pharmacists are often a patient's most accessible point of contact once influenza symptoms begin, giving them a direct role in narrowing the 42% treatment gap identified among high-risk children.²

That includes counseling caregivers on the value of same-day pickup, flagging prescriptions for children in higher-risk age groups or care settings shown to have lower treatment rates, and reinforcing that antiviral therapy works alongside, not in place of, annual influenza vaccination.^1,2

REFERENCES

1. Huang YN, Chang CJ, Dai YL, et al. Early Antiviral Therapy in Pediatric Outpatients and Risk of Influenza-Related Hospitalization. Pediatrics. Published online August 17, 2026. doi:10.1542/peds.2025-075020

2. Antoon JW, Hall M, Feinstein JA, et al. Guideline-Concordant Antiviral Treatment in Children at High Risk for Influenza Complications. Clin Infect Dis. 2023;76(3):e1040-e1046. doi:10.1093/cid/ciac606

3. Centers for Disease Control and Prevention. Influenza antiviral drugs. CDC. Accessed August 18, 2026. https://www.cdc.gov/flu/treatment/antiviral-drugs.html

4. Centers for Disease Control and Prevention. Influenza antiviral medications for children. CDC. Accessed August 18, 2026. https://www.cdc.gov/flu/treatment/children-antiviral.html

5. Świerczyńska M, Mirowska-Guzel DM, Pindelska E. Antiviral Drugs in Influenza. Int J Environ Res Public Health. 2022;19(5):3018. Published 2022 Mar 4. doi:10.3390/ijerph19053018