Symptoms Associated With Respiratory Pathogens in Young Children: 2019–2025

BACKGROUND AND OBJECTIVES: Acute respiratory illnesses (ARI) are common in early life and cause a range of respiratory symptoms. We describe symptomology profiles and medical outcomes attributable to respiratory tract infection episodes. METHODS: Weekly mid-turbinate nasal swabs and biweekly symptom surveys were collected from November 2019 to August 2025 from a longitudinal birth cohort of healthy US infants and children in Cincinnati, Ohio. Nasal swabs were tested for pathogen targets on the Luminex NxTAG Respiratory Pathogen Panel and the Flu SC2 assay. Pathogen-specific infections were linked to the temporally-corresponding symptom surveys. Co-infections were removed to observe only independent pathogen symptomologies. RESULTS: We captured 15 898 ARIs from 1223 unique children. Compared with older children, infants were more likely to experience respiratory distress/dyspnea with influenza A (odds ratio [OR] = 4.73), respiratory syncytial virus (RSV) A (OR = 2.52), RSV B (OR = 2.22), human metapneumovirus (OR = 2.36), and SARS-CoV-2 (OR = 3.99) (all P < 0.01) but not influenza B (P = 0.36) or parainfluenza (P = 0.10). Hospital and emergency department medical attention was similarly associated. Influenza A had greater odds of fever (OR = 2.77, P = 0.01) and anorexia (OR = 2.94, P = 0.01) compared with influenza B. Asymptomatic infections were frequent. Over three-quarters of symptomatic episodes were treated at home. Vomiting and/or diarrhea occurred during one-quarter of RSV and one-third of influenza infection episodes. CONCLUSIONS: Our results highlight extraordinary variability in respiratory tract infection symptoms and outcomes in a US cohort of healthy children. Understanding why some young children suffer severe symptoms and others remain relatively unscathed could unlock actionable opportunities to improve child health. Furthermore, we observed frequent diarrhea and/or vomiting during respiratory tract infections and nuanced differences between influenza A and B symptoms.