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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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References

    1. Rothstein TL. Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers.” BMC Neurol. 2023;23(1):22–33. - DOI - PubMed - PMC
    1. Herrera JE, Niehaus WN, Whiteson J, Azola A, Baratta JM, Fleming TK, et al. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients. PM R. 2021;13(9):1027–43. - DOI - PubMed - PMC
    1. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, W.H.O.C.C.D.W.G. on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022; 22(4):e102-e107.
    1. Kim Y, Bae S, Chang HH, Kim SW. Long COVID prevalence and impact on quality of life 2 years after acute COVID-19. Sci Rep. 2023;13(1):11960–9. - DOI - PubMed - PMC
    1. Moghimi N, Di Napoli M, Biller J, Siegler JE, Shekhar R, McCullough LD, et al. The neurological manifestations of post-acute sequelae of SARS-CoV-2 infection. Current Neurol Neurosci Rep. 2021;21(9):1–17. - DOI

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