Clinical Characteristics and Severity of Rhinovirus/Enterovirus–Associated Hospitalizations: A Multi-country Analysis from the Global Influenza Hospital Surveillance Network, 2017–2024

Abstract Background Rhinoviruses and enteroviruses (RV/EV) are frequently detected in hospitalized patients with acute respiratory illness, yet their clinical burden remains under-characterized, particularly across diverse populations and age groups. Methods We analyzed Global Influenza Hospital Surveillance Network data collected from November 2017 through October 2024 across 13 countries representing high-, upper-middle-, and lower-middle-income settings. Multivariable mixed-effects logistic regression models, stratified by age (<5, 5-64, ≥65 years) and adjusted for sex, comorbidities, influenza coinfection, country income level, and season, identified risk factors for mechanical ventilation and in-hospital death. Results Among 7,929 RV/EV-positive patients, 62.7%, 24.3%, and 13.0% were aged <5, 5-64, and ≥65 years, respectively. In-hospital death was 6.3% among adults aged 65-74 years and 9.2% among those aged ≥75 years. In children aged <5 years, comorbidities strongly predicted mechanical ventilation (adjusted odds ratio [aOR] for ≥2 comorbidities = 4.62, 95% CI: 2.30-9.28) and death (aOR for 1 comorbidity = 3.38, 95% CI: 1.29-8.88). Among adults aged ≥65 years, age ≥75 years predicted in-hospital death (aOR = 2.66, 95% CI: 1.43-4.94). Children aged <5 years from lower-middle-income countries had 10-fold higher probability of in-hospital death than those from high-income countries (aOR = 9.94, 95% CI: 1.87-52.70), the same disparity was seen among older adults from lower-middle-income countries (aOR = 6.83, 95% CI: 1.80-25.88). Conclusions RV/EV infections contribute substantially to severe respiratory disease among hospitalized patients globally, with particularly severe outcomes at both extremes of age and marked inequalities in lower-middle-income countries. RV/EV warrant integration into respiratory virus surveillance and public health strategies.