Decoupling of Respiratory Virus Positivity and Host Inflammatory Response: A 16-Year Longitudinal Study

Given limited evidence on temporal changes in pathogen detection patterns and hospital-based inflammatory burden across the pandemic transition, this study examined their long-term relationship using respiratory multiplex PCR positivity and concurrent C-reactive protein (CRP) levels. We analyzed 19,002 episodes linking respiratory multiplex PCR (mPCR) results and concurrent CRP from October 2008 to December 2024. Pre-pandemic, pandemic, and post-pandemic changes in monthly testing volume, positivity rate, median CRP, high and extreme inflammation by mPCR status, and the correlation between positivity rate and median CRP were assessed. mPCR positivity decreased from 60.62% (pre-pandemic) to 22.45% (pandemic) and remained low at 25.95% thereafter, whereas the median CRP increased from 0.94 to 3.35 and 5.97 mg/dL, respectively. After January 2020, testing volume and positivity rate decreased, whereas the median CRP increased. High inflammation increased from 13.78% to 27.93% and 38.98% in mPCR-negative episodes, and from 4.61% to 7.20% and 27.66% in mPCR-positive episodes, remaining consistently lower in the latter. Monthly positivity rate was strongly negatively correlated with median CRP. Overall, respiratory virus positivity declined, whereas CRP-based inflammatory burden increased, indicating divergent temporal trends across the pandemic transition. These findings should be interpreted descriptively, not causally, as reflecting divergent temporal trajectories of pathogen detection and inflammatory burden.