Abstract Background Respiratory viruses cause major morbidity and mortality in hematologic malignancies. While influenza and SARS-CoV-2 are well-characterized, data on hMPV and RSV remain scarce. We compared their clinical features in this high-risk group. Methods We conducted a multinational study of 130 hMPV and 243 RSV cases (2023–2024), with matched influenza and SARS-CoV-2 cohorts. Data covered patient characteristics, treatment, costs, and 30-day mortality. Results The hMPV and RSV groups had similar demographics and disease profiles, mainly lymphoma and plasma cell disorders. Most infections occurred in winter, with 60% presenting with non-pulmonary symptoms. Severe disease occurred in 52. 3% (hMPV) and 63. 8% (RSV). Hospitalization rates were high (63. 8% vs. 74. 9%), ICU admissions similar (18. 5% vs. 8. 6%), and 30-day mortality was 10. 0% (hMPV) vs. 12. 8% (RSV). Compared to hMPV, influenza cases had higher costs (US 33, 250 vs. 18, 517; p=0. 034), greater antiviral use (74. 1% vs. 1. 9%; p 0. 001), and fewer bacterial co-infections (9. 3% vs. 27. 8%; p=0. 024). SARS-CoV-2 cases also had more antivirals (65. 1% vs. 1. 2%; p 0. 001), fewer bacterial co-infections (9. 3% vs. 25. 6%; p=0. 008), but slightly less severe disease (44. 2% vs. 47. 7%; p=0. 003). RSV was linked to more secondary infections than influenza (bacterial 21. 3% vs. 12. 4%, p=0. 033; viral 5. 6% vs. 1. 1%, p=0. 035), higher ward costs, and shorter intermediate care stays (5 vs. 12 days; p=0. 010). Influenza patients were more often vaccinated (11. 2% vs. 0. 6%; p 0. 001) and treated with antivirals (82. 0% vs. 15. 2%; p 0. 001). RSV showed more pulmonary symptoms (33. 0% vs. 19. 2%; p 0. 001), severe cases (62. 1% vs. 40. 4%; p 0. 001), and hospitalizations (74. 4% vs. 54. 2%; p 0. 001) than SARS-CoV-2, which had higher intermediate care costs and more targeted therapy (68. 5% vs. 14. 3%; p 0. 001). hMPV and RSV had comparable clinical profiles and outcomes, though hMPV showed slightly less treatment and more bacterial co-infections. Conclusion In hematologic malignancy patients, hMPV and RSV cause substantial morbidity, high hospitalization and ICU rates, and 30-day mortality (10. 0% and 12. 8%), comparable to influenza and SARS-CoV-2. Yet, they remain under-treated, highlighting the need for improved diagnostics and targeted care. Disclosures Jon Salmanton-Garcia, MSc, MPH, PhD, menarini, gilead, astrazeneca, pfizer: Honoraria Oliver A. Cornely, Prof. Dr. , Al-Jazeera Pharmaceuticals/Hikma: Honoraria|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Board Member|Cidara: Grant/Research Support|Elion: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|Grupo Biotoscana/United Medical/Knight: Honoraria|Melinta: Advisor/Consultant|Melinta: Board Member|MSD: Honoraria|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Board Member|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria
Salmanton‐García et al. (Thu,) studied this question.