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

## TL;DR

Post-COVID-19 patients have higher levels of IL-1β, a key inflammatory marker, for up to 9 months compared to healthy people, suggesting ongoing immune activation.

## Contribution

This study is the first to show persistent IL-1β elevation in post-COVID-19 patients over a 9-month period using a nationwide registry.

## Key findings

- IL-1β levels were significantly higher in post-COVID-19 patients across all age groups compared to healthy controls.
- Elevated IL-1β levels remained stable for 9 months after infection, indicating sustained immune activation.
- Other inflammatory markers showed no significant differences or were lower in post-COVID-19 patients.

## Abstract

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).

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.

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.

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.

Japan Registry of Clinical Trials: jRCT1030220711

Post‐COVID‐19 patients show persistent elevation of interleukin‐1β compared to healthy controls, sustained over 9 months without normalization. This low‐grade inflammatory response suggests ongoing immune activation following SARS‐CoV‐2 infection, providing insights into potential mechanisms underlying post‐COVID‐19 neuropsychiatric symptoms and highlighting the need for longitudinal inflammatory monitoring.