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. 2025 Feb;52(3):810-822.
doi: 10.1007/s00259-024-06937-x. Epub 2024 Oct 15.

Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms

Anna Lisa Martini #  1 , Giulia Carli #  2 , Silvia Paola Caminiti  3 , Lorenzo Kiferle  4 , Andrea Leo  1 , Daniela Perani  5   6   7 , Stelvio Sestini  8
Affiliations

Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms

Anna Lisa Martini et al. Eur J Nucl Med Mol Imaging. 2025 Feb.

Abstract

Purpose: Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients.

Methods: We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent FDG-PET scans, and classified to timing infection as follows: acute (7 pts), subacute (17 pts), long-term (20 pts) phases. Interregional correlation analysis (IRCA) and ROI-based IRCA were applied on FDG-PET data to extract metabolic connectivity in resting state networks (ADMN, PDMN, EXN, ATTN, LIN, ASN) of neuro-COVID pts in acute/subacute and long-term groups compared with healthy controls (HCs). Univariate approach was used to investigate metabolic alterations from the acute to sub-acute and long-term phase.

Results: The acute/subacute phase was characterized by hyperconnectivity in EXN and ATTN networks; the same networks showed hypoconnectivity in the chronic phase. EXN and ATTN hypoconnectivity was consistent with clinical findings in long-COVID patients, e.g. altered performances in neuropsychological tests of executive and attention domains. The ASN and LIN presented hyperconnectivity in acute/subacute phase and normalized in long-term phase. The ADMN and PDMN presented a preseverved connectivity. Univariate analysis showed hypometabolism in fronto-insular cortex in acute phase, which reduced in sub-acute phase and disappeared in long-term phase.

Conclusion: A compensatory EXN and ATTN hyperconnectivity was found in the acute/subacute phase and hypoconnectivity in long-term. Hypoconnectivity and absence of hypometabolism suggest that connectivity derangement in frontal networks could be related to protraction of neurological symptoms in long-term COVID patients.

Keywords: Brain metabolic connectivity; FDG-PET; Long-COVID; Neuro-COVID; Resting state network.

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Conflict of interest statement

Declarations. Ethical: The present study was approved by the local ethics committee of the Nuclear Medicine Unit, Ospedale Santo Stefano Prato, Italy (N 763, 29/03/2022) and complies with the Helsinki Declaration. Informed consent: Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for publication of the images in Figs. 1, 2 and 3. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

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