Associations between virus single infection or coinfection and respiratory symptoms in young children: A community-based cohort study

Objectives Virus coinfections are common in young children. We quantified single and coinfections and their association with acute respiratory illness (ARI) in a prospective community-based cohort. Methods Healthy children (aged <4 years) were randomly invited for participation. Between October and May of 2021-2024, weekly nasal samples and daily symptom diaries were collected over 16 week, regardless of symptoms. Samples were tested via polymerase chain reaction for 17 respiratory viruses. Associations between ARI and infection status (coinfection, single virus, none) were analyzed using mixed-effects logistic regression. Results A total of 228 children (median age: 19.9 months) contributed 24,432 diaries and 3332 nasal samples. Of 1241 virus infection episodes, 247 (19.9%) were coinfections and 613 (49.4%) were associated with ARI. Single virus vs no infection increased the odds of ARI (odds ratio [OR]: 2.15; 95% confidence interval [CI]: 1.69-2.73). Three virulence categories emerged: mild (not associated with ARI; enterovirus, adenovirus, bocavirus), moderate (ORs: 1.36-1.81; rhinovirus, seasonal coronaviruses, SARS-CoV-2), and severe (ORs: 3.44-5.01; influenza, human metapneumovirus, parainfluenza, respiratory syncytial virus). Coinfection further increased the odds of ARI by 1.87 (95% CI: 1.22-2.89), even when accounting for virulence category. Conclusions About half of respiratory viral infections in young children are associated with ARI. This likelihood varies by virus, reflecting virulence differences. Coinfection increases the odds of ARI beyond individual virus effects, suggesting virus interactions mediate severity.