Persistent Interleukin-1β Elevation in Post-COVID-19 Patients: Findings From a Nationwide Registry Study in Japan

Aim: 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). Methods: 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. Results: 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. Conclusion: 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. Trial Registration: Japan Registry of Clinical Trials: jRCT1030220711.