Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings

• Published in: Brain Structure and Function Vol. 230; no. 7; p. 128
• Main Authors: Siqueira, Izabella Fernanda Bastos, Figueiredo, Lais Almeida, Fernandes, Camila Emanuele Moreira, Cintra, Leandro Pinheiro, de Oliveira, Glauber Fernandes, Rios, Maria Angélica, Maciel, Ricardo, Ferretjans, Rodrigo, Guimarães, Nathalia Sernizon, Magno, Luiz Alexandre Viana
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 07.08.2025; Springer Nature B.V
• Subjects: Age; Bias; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Brain - metabolism; Brain research; Cell Biology; Cognition; Cortex (frontal); COVID-19; COVID-19 - complications; COVID-19 - diagnostic imaging; COVID-19 - metabolism; Fluorodeoxyglucose F18; Glucose - metabolism; Humans; Long COVID; Males; Meta-analysis; Metabolism; Neurology; Neurosciences; Patients; Positron emission tomography; Positron-Emission Tomography - methods; Post-Acute COVID-19 Syndrome; Radiopharmaceuticals; Review; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spatial distribution; Subject heading schemes; Systematic review; Temporal lobe; Italy; Belgium; France; Germany; Neuroimaging; Post-Acute COVID-19 syndrome; Neurologic manifestations; 18F-FDG; Positron-Emission tomography
• ISSN: 1863-2661; 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-025-02997-3

Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges’ g  = 1.34; 95% CI : 0.79–1.88; p  < 0.001), despite high heterogeneity ( I 2  = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.