Nosocomial Respiratory Virus Infections in Hematologic Malignancies: Risk Factors for Progression to Lower Respiratory Tract Infection

Respiratory virus (RV) infections cause significant morbidity in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients. However, predictors of progression from upper respiratory tract infection (URTI) to lower respiratory tract infection (LRTI) in the nosocomial setting remain poorly characterized, particularly beyond HCT-only cohorts. The effectiveness of URTI-stage antiviral therapy is also unclear, and nosocomial seasonal patterns in hematology settings have not been well described. This study aimed to identify risk factors for URTI-to-LRTI progression across influenza virus (IFV), respiratory syncytial virus (RSV), and parainfluenza virus (PIV) in hospitalized patients with HM. Secondary objectives included evaluation of URTI-stage antiviral therapy and characterization of nosocomial seasonal patterns. This multicenter retrospective study (South Korea, 2016 to 2024) included hospitalized adults with HM and laboratory-confirmed nosocomial IFV, RSV, or PIV detection >48 hours after admission, excluding community-acquired episodes and pre-existing pneumonia. URTI-to-LRTI progression within 30 days was analyzed using Fine-Gray subdistribution hazard models with death as a competing event. Antiviral effects were evaluated via propensity-weighted landmark analyses. Seasonality was assessed using Poisson harmonic regression. Of 473 eligible episodes, 359 presenting as URTI were analyzed; 99 (27.6%) progressed to LRTI. Systemic glucocorticoid exposure (≥20 mg/d prednisolone equivalent; subdistribution hazard ratio [sHR], 2.41; 95% confidence interval [CI], 1.22 to 4.74) and neutropenia (