TY - JOUR
T1 - Persistent Interleukin-1β Elevation in Post-COVID-19 Patients
T2 - Findings From a Nationwide Registry Study in Japan
AU - Takamatsu, Naoki
AU - Kimura, Hiroki
AU - Oba, Mari S.
AU - Chiba, Hiroyuki
AU - Umemoto, Ikue
AU - Moriyama, Yuki
AU - Matsunaga, Nobuaki
AU - Morioka, Shinichiro
AU - Mori, Daisuke
AU - Hara, Kazuhiro
AU - Ogura, Aya
AU - Yoshida, Kazufumi
AU - Watanabe, Hirohisa
AU - Maesawa, Satoshi
AU - Ikeda, Masashi
AU - Katsuno, Masahisa
AU - Ohmagari, Norio
AU - Takao, Masaki
AU - Kito, Shinsuke
AU - Ozaki, Norio
AU - Kuga, Hironori
N1 - Publisher Copyright:
© 2026 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.
PY - 2026/3
Y1 - 2026/3
N2 - 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.
AB - 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.
KW - biomarkers
KW - COVID-19
KW - inflammation
KW - interleukin-1beta
KW - SARS-CoV-2
UR - https://www.scopus.com/pages/publications/105031528881
UR - https://www.scopus.com/pages/publications/105031528881#tab=citedBy
U2 - 10.1002/npr2.70082
DO - 10.1002/npr2.70082
M3 - Article
C2 - 41761677
AN - SCOPUS:105031528881
SN - 2574-173X
VL - 46
JO - Neuropsychopharmacology Reports
JF - Neuropsychopharmacology Reports
IS - 1
M1 - e70082
ER -
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