急性炎症および前頭線条体接続性は、軽度COVID-19から遷延性疲労への移行において：遷延性fMRI研究
Qiange Zhu1, Tao Lu1, Huijie Yuan1
1Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Background:
Persistent fatigue is one of the most common and disabling sequelae of COVID-19, yet its neurobiological mechanisms remain poorly understood. Emerging evidence implicates systemic inflammation and fronto-striatal dysfunction in fatigue across diverse clinical conditions. However, the links between early inflammatory responses, brain connectivity, and the acute-to-chronic trajectory of post-COVID fatigue are unclear.
Methods:
In a multi-center longitudinal cohort of 193 young-to-middle-aged adults with mild COVID-19, we assessed acute-phase C-reactive protein (CRP), fatigue severity (FAS) at <1 month (acute, FAS-1) and 3 months (chronic, FAS-2) post-infection, and resting-state fMRI at 3 months. Functional connectivity (FC) differences between participants with persistent (n = 48) and non-persistent fatigue (n = 145) were examined, and mediation analyses were performed to evaluate pathways linking CRP, FC alterations, and fatigue progression.
Results:
Acute-phase CRP levels were elevated in the persistent fatigue group and positively correlated with fatigue severity at both time points. Compared with the non-persistent group, individuals with persistent fatigue showed reduced functional connectivity (FC) between the left superior frontal gyrus (SFG L) and striatal regions (caudate L and putamen L). This SFG L-striatal FC was negatively correlated with fatigue severity. Crucially, a chain mediation model suggested that the association between CRP on chronic fatigue was statistically mediated through two sequential pathways: (1) via acute fatigue alone, and (2) via acute fatigue followed by reduced SFG L-striatal FC.
Conclusion:
In this cohort of mild COVID-19 survivors, this study identifies acute inflammation (elevated CRP) as a significant predictor of post-COVID fatigue and suggests that reduced fronto-striatal connectivity may mediate the transition from acute to chronic fatigue. These findings highlight the fronto-striatal circuit as a potential imaging biomarker and point to the acute phase as a critical window for anti-inflammatory or neuromodulatory interventions. Further longitudinal and interventional studies are needed to validate these mechanisms and therapeutic strategies.
