Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review.

Studies have shown that the predictive value of "clinical diagnoses" of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence-based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus-1, coronaviruses, or parainfluenza virus: (a) systematic review and meta-analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data-driven analysis of an inception cohort of 6073 children with ILI (aged 0-18 years, 56% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our "real-world" dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms.