Comparison of the Clinical Course of Viral Respiratory Infections in Hospitalized Patients During the 2025/2026 Season in Poland

Background/Objectives: SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV) remain major causes of adult hospitalizations, but contemporary comparative data are limited. This study compared the epidemiological characteristics, clinical presentation, and outcomes of adults hospitalized with these infections during the 2025/2026 epidemic season in Poland. Methods: We conducted a retrospective multicenter study of consecutive adults hospitalized with laboratory-confirmed COVID-19, influenza, or RSV infection between September 2025 and April 2026. Demographic characteristics, comorbidities, vaccination status, clinical features, laboratory findings, and outcomes were analyzed. Independent predictors of in-hospital mortality were identified using multivariable logistic regression. Results: The study included 604 patients: 255 with COVID-19, 314 with influenza, and 35 with RSV infection. Distinct seasonal patterns were observed, with COVID-19 peaking in autumn, influenza in winter, and RSV in early spring. Most hospitalized patients were elderly and unvaccinated. RSV patients were older, more frequently affected by multimorbidity, ischemic heart disease, and cancer, and showed the greatest respiratory impairment, including the highest rates of hypoxemia and pneumonia. Influenza was characterized by more frequent fever, headache, and myalgia. Despite lower pneumonia rates, COVID-19 was associated with the highest in-hospital mortality (13.7%) and remained an independent predictor of death (aOR = 3.23, 95%CI: 1.68–6.22). Antibiotic use was common across all cohorts (62–77%). Conclusions: COVID-19 remained associated with the highest mortality among hospitalized adults, whereas RSV contributed substantially to respiratory morbidity in older individuals. These findings support improved vaccination uptake, continued surveillance, hospital preparedness, and antimicrobial stewardship.