Time-dependent recovery of brain hypometabolism in neuro-COVID-19 patients

• Published in: European journal of nuclear medicine and molecular imaging Vol. 50; no. 1; pp. 90 - 102
• Main Authors: Martini, Anna Lisa, Carli, Giulia, Kiferle, Lorenzo, Piersanti, Patrizia, Palumbo, Pasquale, Morbelli, Silvia, Calcagni, Maria Lucia, Perani, Daniela, Sestini, Stelvio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2022; Springer Nature B.V
• Subjects: Amygdala; Body mass index; Body size; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain stem; C-reactive protein; Cardiology; Cerebellum; Cognition; Cognitive ability; Coronaviruses; Cortex (insular); COVID-19; COVID-19 - diagnostic imaging; Evaluation; Fluorodeoxyglucose F18 - metabolism; Humans; Hypometabolism; Hypoxia; Imaging; Inflammation; Inflammation - metabolism; Medicine; Medicine & Public Health; Neurological diseases; Neurology; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Oxygen content; Patients; Positron emission tomography; Radiology; Signs and symptoms; Synergistic effect; Time dependence; Viral diseases; [; Hypermetabolism; Neuro-COVID; Hypometabolism; Recovery; F]FDG; [18F]FDG
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-022-05942-2

Purpose We evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease. Methods Twenty-six patients with neurological symptoms (neuro-COVID-19) and [ 18 F]FDG-PET were included. Seven patients were acute (< 1 month (m) after onset), 12 subacute (4 ≥ 1-m, 4 ≥ 2-m and 4 ≥ 3-m) and 7 with neuro-post-COVID-19 (3 ≥ 5-m and 4 ≥ 7–9-m). One patient was evaluated longitudinally (acute and 5-m). Brain hypo- and hypermetabolism were analysed at single-subject and group levels. Correlations between severity/extent of brain hypo- and hypermetabolism and biological (oxygen saturation and C-reactive protein) and clinical variables (global cognition and Body Mass Index) were assessed. Results The “fronto-insular cortex” emerged as the hypometabolic hallmark of neuro-COVID-19. Acute patients showed the most severe hypometabolism affecting several cortical regions. Three-m and 5-m patients showed a progressive reduction of hypometabolism, with limited frontal clusters. After 7–9 months, no brain hypometabolism was detected. The patient evaluated longitudinally showed a diffuse brain hypometabolism in the acute phase, almost recovered after 5 months. Brain hypometabolism correlated with cognitive dysfunction, low blood saturation and high inflammatory status. Hypermetabolism in the brainstem, cerebellum, hippocampus and amygdala persisted over time and correlated with inflammation status. Conclusion Synergistic effects of systemic virus-mediated inflammation and transient hypoxia yield a dysfunction of the fronto-insular cortex, a signature of CNS involvement in neuro-COVID-19. This brain dysfunction is likely to be transient and almost reversible. The long-lasting brain hypermetabolism seems to reflect persistent inflammation processes.