Age-Structured Clinical Background Is More Strongly Associated with C-Reactive Protein Levels than Individual Respiratory Viruses During Respiratory Virus Testing

We aimed to characterize age-stratified C-reactive protein (CRP) patterns across respiratory virus infections, assess age-related CRP shifts in virus-not-detected-by-PCR episodes, and evaluate the independent associations of age and virus type with CRP levels. We retrospectively analyzed 19,002 test-level episodes with paired respiratory PCR and serum CRP results from a single tertiary-care center between 2008 and 2024. Episodes were classified as virus-not-detected-by-PCR or virus-positive according to multiplex PCR results; the former was not considered a healthy control and may include off-panel infections, bacterial/mixed infections, false-negative results, or non-infectious inflammation. Descriptive analyses and multivariable linear regression of log-transformed CRP were used to assess adjusted associations. Median CRP increased with age in both virus-positive and virus-not-detected-by-PCR episodes, rising from 0.38 to 7.42 mg/dL across age groups in the latter. Age showed the strongest association with CRP. Adenovirus showed a positive adjusted association, whereas influenza A/B, respiratory syncytial virus A/B, and parainfluenza virus types 1 and 3 showed selective negative associations. Overall, CRP variation was more strongly associated with age-related clinical background than with virus type, although selective virus-associated differences were observed, supporting the interpretation of CRP as a non-specific, composite host-response indicator within broader clinical contexts.