Hirohisa Watanabe

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Aim</jats:title> <jats:p>COVID‐19 has been associated with dysregulated immune responses, with increasing evidence indicating sustained inflammasome activation and subsequent pro‐inflammatory cytokine production. This study aimed to characterize the temporal profile of inflammatory markers, particularly interleukin (IL)‐1β, in post‐COVID‐19 patients compared with pre‐pandemic healthy controls, using data from the Psychiatric Symptoms for COVID‐19 Registry Japan (PSCORE‐J).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Blood samples were analyzed from 119 post‐COVID‐19 patients (median age 45 years) recruited during 2023 and 374 pre‐pandemic healthy controls (median age 65 years). For post‐COVID‐19 patients, samples were collected at baseline, 3 months, and 9 months. Multiple inflammatory markers were assessed, including IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12, TNF‐α, IFN‐γ, IFN‐β, IP‐10, ACE2, and eotaxin. Age‐ and sex‐adjusted analyses were performed on log‐transformed IL‐1β levels.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>IL‐1β levels were significantly elevated in post‐COVID‐19 patients compared with healthy controls across all age groups (under 30s: 0.69 ± 0.33 vs. 0.25 ± 0.03; 30s: 0.70 ± 0.63 vs. 0.26 ± 0.09; 40s: 0.84 ± 0.76 vs. 0.30 ± 0.23; 50s: 0.67 ± 0.65 vs. 0.26 ± 0.10; 60 or over: 0.54 ± 0.30 vs. 0.26 ± 0.23 pg/mL). This elevation was sustained throughout the 9‐month follow‐up (baseline: 0.500 [0.33–0.890]; 3 months: 0.630 [0.28–1.290]; 9 months: 0.54 [0.29–0.96] pg/mL) compared with controls (0.24 [0.21–0.27] pg/mL). Other inflammatory markers showed either no significant differences or were paradoxically lower in patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>SARS‐CoV‐2 infection is associated with persistent elevation of IL‐1β levels that remains stable over a 9‐month period, suggesting sustained inflammasome activation. These findings provide novel insight into post‐COVID‐19 inflammatory processes and may have important implications for understanding both acute and chronic manifestations of the disease.</jats:p> </jats:sec> <jats:sec> <jats:title>Trial Registration</jats:title> <jats:p>Japan Registry of Clinical Trials: jRCT1030220711</jats:p> </jats:sec>