Age- and Virus-Composition-Aware Interpretation of Respiratory Viral Co-Detection Using Same-Day C-Reactive Protein Profiles: A 2008–2024 Multiplex PCR Laboratory Cohort Study

Objectives: To determine whether patient age and viral composition provide more informative context than detected target number alone for interpreting same-day C-reactive protein (CRP) profiles when multiple respiratory viruses are detected. Methods: We retrospectively analyzed 19,002 same-day respiratory multiplex polymerase chain reaction (PCR)–serum CRP episodes collected at a Korean tertiary care hospital from October 2008 to December 2024. Episodes were classified as PCR-not-detected, single-virus detection, or viral co-detection. Among virus-positive episodes, associations with log-transformed CRP were evaluated using adjusted regression, leave-one-virus-out analyses, and a complete-panel mixed-effects model accounting for viral composition and repeated measurements. Results: Unadjusted CRP distributions were similar between single-virus detection and co-detection. After age- and sex-adjustment, co-detection was associated with 11.8% higher CRP. Excluding adenovirus-positive episodes attenuated the estimate to 2.7% (95% CI, −5.8 to 12.0; p = 0.541). In the complete-panel analysis of 1839 episodes from 1636 patients, co-detection was not independently associated with CRP, whereas adenovirus was associated with 75.1% higher CRP. Age group also showed strong graded associations with CRP levels overall. Conclusions: When multiple respiratory viruses are co-detected, same-day CRP profiles are better contextualized by patient age and the specific viral composition than by the number of detected targets alone.