Human Metapneumovirus in the Post-pandemic Era:: A Multicenter Comparative Study With Respiratory Syncytial Virus in Argentina, 2022–2025

Background: Human metapneumovirus (hMPV), identified in 2001, is an important cause of acute lower respiratory infections (ALRI) in children worldwide and is generally considered the second most frequent viral cause after respiratory syncytial virus (RSV). Comparative data between hMPV and RSV in the post-pandemic period remain scarce in Latin America, particularly after the introduction of maternal RSV immunization. Methods: We conducted a prospective multicenter surveillance study in 5 tertiary pediatric hospitals in Argentina between 2022 and 2025. Children hospitalized with reverse transcription polymerase chain reaction–confirmed hMPV or RSV-associated ALRI were included. Epidemiologic characteristics, clinical presentation, respiratory support requirements, outcomes and seasonal patterns were compared. Independent predictors of hMPV versus RSV infection were evaluated using multivariable logistic regression. Results: Among 19,021 ALRI hospitalizations, 661 (3.5%) were hMPV and 2397 (12.6%) were RSV cases. hMPV patients were older (median 10 vs 8 months; P < 0.001), had more comorbidities (59% vs. 47%; P < 0.001) and had prior respiratory hospitalizations (42% vs. 27%; P < 0.001). Fever was more frequent in hMPV (74% vs. 65%; P < 0.001), and focal pneumonia predominated over bronchiolitis. RSV required more advanced respiratory support. Mortality was extremely low and comparable. Independent predictors of hMPV included age 6–23 months and prior respiratory hospitalizations; hMPV risk was lower in 2023–2025 versus 2022. hMPV peaked later than RSV. Conclusions: This emerging respiratory virus demonstrates distinct epidemiologic and clinical characteristics, predominantly affecting older children with respiratory vulnerability. In the era of RSV prevention strategies, hMPV may represent an increasingly important contributor to the residual burden of severe pediatric ALRI, highlighting the need for development of preventive interventions.