18F-FDG
Angiotensin-converting enzyme
Anosmia
COVID-19
Complaints
Dysautonomia
Fatigue
Long COVID
Memory
PET
SARS-CoV-2
Stress
Journal
European journal of nuclear medicine and molecular imaging
ISSN: 1619-7089
Titre abrégé: Eur J Nucl Med Mol Imaging
Pays: Germany
ID NLM: 101140988
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
29
11
2020
accepted:
19
01
2021
pubmed:
28
1
2021
medline:
14
7
2021
entrez:
27
1
2021
Statut:
ppublish
Résumé
In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.
Identifiants
pubmed: 33501506
doi: 10.1007/s00259-021-05215-4
pii: 10.1007/s00259-021-05215-4
pmc: PMC7837643
doi:
Substances chimiques
Fluorodeoxyglucose F18
0Z5B2CJX4D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2823-2833Subventions
Organisme : PHRC
ID : 07/09
Commentaires et corrections
Type : CommentIn
Références
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun. 2020;89:594–600. https://doi.org/10.1016/j.bbi.2020.07.037 .
doi: 10.1016/j.bbi.2020.07.037
pubmed: 32738287
pmcid: 7390748
Khateb M, Bosak N, Muqary M. Coronaviruses and central nervous system manifestations. Front Neurol. 2020;11:715. https://doi.org/10.3389/fneur.2020.00715 .
doi: 10.3389/fneur.2020.00715
pubmed: 32655490
pmcid: 7324719
Liguori C, Pierantozzi M, Spanetta M, Sarmati L, Cesta N, Iannetta M, et al. Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection. Brain Behav Immun. 2020;88:11–6. https://doi.org/10.1016/j.bbi.2020.05.037 .
doi: 10.1016/j.bbi.2020.05.037
pubmed: 32416289
pmcid: 7235586
Meeting the challenge of long COVID. Nat Med. 2020;26:1803. doi: https://doi.org/10.1038/s41591-020-01177-6 .
The Lancet. Facing up to long COVID. Lancet. 2020;396:1861. doi: https://doi.org/10.1016/S0140-6736(20)32662-3 .
Serrano-Castro PJ, Estivill-Torrús G, Cabezudo-García P, Reyes-Bueno JA, Ciano Petersen N, Aguilar-Castillo MJ, et al. Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? Neurologia. 2020;35:245–51. https://doi.org/10.1016/j.nrl.2020.04.002 .
doi: 10.1016/j.nrl.2020.04.002
pubmed: 32364119
pmcid: 7164900
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11:995–8. https://doi.org/10.1021/acschemneuro.0c00122 .
doi: 10.1021/acschemneuro.0c00122
pubmed: 32167747
Guedj E, Million M, Dudouet P, Tissot-Dupont H, Bregeon F, Cammilleri S, et al. 18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders? Eur J Nucl Med Mol Imaging. 2020;30:1–4. https://doi.org/10.1007/s00259-020-04973-x .
doi: 10.1007/s00259-020-04973-x
Guedj E, Verger A, Cammilleri S. PET imaging of COVID-19: the target and the number. Eur J Nucl Med Mol Imaging. 2020;47:1636–7. https://doi.org/10.1007/s00259-020-04820-z .
doi: 10.1007/s00259-020-04820-z
pubmed: 32303786
Morbelli S, Ekmekcioglu O, Barthel H, Albert NL, Boellaard R, Cecchin D, et al. COVID-19 and the brain: impact on nuclear medicine in neurology. Eur J Nucl Med Mol Imaging. 2020;47:2487–92. https://doi.org/10.1007/s00259-020-04965-x .
doi: 10.1007/s00259-020-04965-x
pubmed: 32700058
Liao X, Wang B, Kang Y. Novel coronavirus infection during the 2019-2020 epidemic: preparing intensive care units-the experience in Sichuan Province, China. Intensive Care Med. 2020;46:357–60. https://doi.org/10.1007/s00134-020-05954-2 .
doi: 10.1007/s00134-020-05954-2
pubmed: 32025779
pmcid: 7042184
Landis BN, Leuchter I, San Millán Ruíz D, Lacroix JS, Landis T. Transient hemiageusia in cerebrovascular lateral pontine lesions. J Neurol Neurosurg Psychiatry. 2006;77:680–3. https://doi.org/10.1136/jnnp.2005.086801 .
doi: 10.1136/jnnp.2005.086801
pubmed: 16614035
pmcid: 2117445
Mainland JD, Johnson BN, Khan R, Ivry RB, Sobel N. Olfactory impairments in patients with unilateral cerebellar lesions are selective to inputs from the contralesional nostril. J Neurosci. 2005;25:6362–71. https://doi.org/10.1523/JNEUROSCI.0920-05.2005 .
doi: 10.1523/JNEUROSCI.0920-05.2005
pubmed: 16000626
pmcid: 6725278
Bodranghien F, Bastian A, Casali C, Hallett M, Louis ED, Manto M, et al. Consensus paper: revisiting the symptoms and signs of cerebellar syndrome. Cerebellum. 2016;15:369–91. https://doi.org/10.1007/s12311-015-0687-3 .
doi: 10.1007/s12311-015-0687-3
pubmed: 26105056
pmcid: 5565264
Marvel CL, Morgan OP, Kronemer SI. How the motor system integrates with working memory. Neurosci Biobehav Rev. 2019;102:184–94. https://doi.org/10.1016/j.neubiorev.2019.04.017 .
doi: 10.1016/j.neubiorev.2019.04.017
pubmed: 31039359
pmcid: 6604620
Borsook D, Sava S, Becerra L. The pain imaging revolution: advancing pain into the 21st century. Neuroscientist. 2010;16:171–85. https://doi.org/10.1177/1073858409349902 .
doi: 10.1177/1073858409349902
pubmed: 20400714
pmcid: 3370428
Guedj E, Cammilleri S, Niboyet J, Dupont P, Vidal E, Dropinski JP, et al. Clinical correlate of brain SPECT perfusion abnormalities in fibromyalgia. J Nucl Med. 2008;49:1798–803. https://doi.org/10.2967/jnumed.108.053264 .
doi: 10.2967/jnumed.108.053264
pubmed: 18927329
Canto CB, Onuki Y, Bruinsma B, van der Werf YD, De Zeeuw CI. The sleeping cerebellum. Trends Neurosci. 2017;40:309–23. https://doi.org/10.1016/j.tins.2017.03.001 .
doi: 10.1016/j.tins.2017.03.001
pubmed: 28431742
Torrico TJ, Abdijadid S. Neuroanatomy, Limbic System. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382:2268–70. https://doi.org/10.1056/NEJMc2008597 .
doi: 10.1056/NEJMc2008597
pubmed: 32294339
Grimaldi S, Lagarde S, Harle JR, Boucraut J, Guedj E. Autoimmune encephalitis concomitant with SARS-CoV-2 infection: insight from 18 F-FDG PET Imaging and Neuronal Autoantibodies. J Nucl Med. 2020;61(12):1726–9. https://doi.org/10.2967/jnumed.120.249292 .
doi: 10.2967/jnumed.120.249292
pubmed: 32709734
Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18–22. https://doi.org/10.1016/j.bbi.2020.03.031 .
doi: 10.1016/j.bbi.2020.03.031
pubmed: 32240762
pmcid: 7146689
Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611–27. https://doi.org/10.1016/S2215-0366(20)30203-0 .
doi: 10.1016/S2215-0366(20)30203-0
pubmed: 32437679
pmcid: 7234781
Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011;11:37. https://doi.org/10.1186/1471-2377-11-37 .
doi: 10.1186/1471-2377-11-37
pubmed: 21435231
pmcid: 3071317
Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020;87:34–9. https://doi.org/10.1016/j.bbi.2020.04.027 .
doi: 10.1016/j.bbi.2020.04.027
pubmed: 32298803
pmcid: 7152874
Lahav Y. Psychological distress related to COVID-19 - the contribution of continuous traumatic stress. J Affect Disord. 2020;277:12316. https://doi.org/10.1016/j.jad.2020.07.141 .
doi: 10.1016/j.jad.2020.07.141
Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020;1:e245–e253. https://doi.org/10.1016/S2666-5247(20)30115-4 .
Guedj E, Barrie M, Fuentes S, Chinot O, Mundler O. A case of cerebello-thalamo-cortical diaschisis. Clin Nucl Med. 2008;33:717–8. https://doi.org/10.1097/RLU.0b013e318184ba05 .
doi: 10.1097/RLU.0b013e318184ba05
pubmed: 18806580
Morbelli S, Drzezga A, Perneczky R, Frisoni GB, Caroli A, van Berckel BN, et al. Resting metabolic connectivity in prodromal Alzheimer’s disease. A European Alzheimer Disease Consortium (EADC) project. Neurobiol Aging. 2012;33:2533–50. https://doi.org/10.1016/j.neurobiolaging.2012.01.005 .
doi: 10.1016/j.neurobiolaging.2012.01.005
pubmed: 22365486
Guedj E, Barbeau EJ, Didic M, Felician O, de Laforte C, Ranjeva JP, et al. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation? Eur J Nucl Med Mol Imaging. 2009;36:1101–12. https://doi.org/10.1007/s00259-009-1060-x .
doi: 10.1007/s00259-009-1060-x
pubmed: 19224210