Abstract
OBJECTIVE: Neuropsychiatric symptoms are among the most prevalent sequelae of COVID-19, particularly among hospitalized patients. Recent research has identified volumetric brain changes associated with COVID-19. However, it currently remains poorly understood how brain changes relate to post-COVID fatigue and cognitive deficits. We, therefore, aimed to assess structural brain changes after hospitalization for COVID-19 and their associations with cognitive performance and fatigue. METHODS: We analyzed data from n = 57 patients previously hospitalized for COVID-19 (63% male, mean age 52 years) from the prospective, multicentric high-resolution platform of the German National Pandemic Cohort Network (NAPKON-HAP) and n = 57 matched healthy control participants (HC). We assessed cortical thickness and subcortical volumes in high-resolution T1-weighted MRI and their associations with cognitive performance (Montreal Cognitive Assessment) and fatigue (Fatigue Severity Scale). RESULTS: Patients exhibited statistically significant reductions of cortical thickness in parahippocampal gyri and the temporal lobe (all p[FDR-corrected] < 0.05) as well as reduced hippocampal volumes compared to HC (left, Cohen's d [95% CI] = 0.50 [0.12-0.8]; right d = 0.43 [0.05-0.80]). Higher acute COVID-19 severity was associated with reduced cortical thickness, particularly in the olfactory system. Furthermore, reduced cortical thickness of the temporal poles and the anterior and posterior cingulate gyrus was associated with more severe post-acute fatigue. INTERPRETATION: Our results identify long-lasting macrostructural brain changes after moderate to severe COVID-19 that correlate with acute disease severity and long-term fatigue. Early identification and targeted interventions for patients at risk of persistent brain changes are needed. TRIAL REGISTRATION: NAPKON-HAP is registered at clinicaltrials.gov (NCT04747366).