About the source and consequences of 18F-FDG brain PET hypometabolism in short and long COVID-19

Fontana, Igor C.; Souza, Débora Guerini de; Pellerin, Luc; Souza, Diogo Onofre Gomes de; Zimmer, Eduardo R.

doi:10.1007/s00259-021-05342-y

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…As key regulators of CNS metabolism, alterations in astrocyte metabolism contribute to the 18F-FDG PET signal ( 79 – 81 ). Therefore, dysfunctions in astrocyte energy metabolism, like those observed here, could explain, at least partially, the brain hypometabolism in COVID-19 patients ( 78 , 82 – 85 ).…”

Section: Discussionsupporting

confidence: 52%

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Crunfli

Carregari

Veras

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

179

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Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of “long COVID-19” syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell–derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike–NRP1 interaction. SARS-CoV-2–infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

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Section: Discussionsupporting

confidence: 52%

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Crunfli

Carregari

Veras

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

179

View full text Add to dashboard Cite

show abstract

“…In fact, studies reported the signs of reactive astrogliosis in post‐mortem tissue of COVID‐19 patients, 92 cellular models, and brain organoids 93 . In fact, brain PET in long COVID patients revealed hypometabolism, which is consistent with astroglial inflammation 83 . These factors may lead to neuropsychiatric symptoms in long COVID.…”

Section: Potential Mechanism Of Long Covid and Its Neuropsychiatric S...mentioning

confidence: 88%

“…82 Given that the brain glucose metabolism can be caused by astroglia as well as neuronal dysfunction, it can be speculated that astroglial inflammation may be involved in brain dysfunction in long COVID cases and could possibly lead to more severe sequelae such as neurodegenerative diseases. 83 On the other hand, another study reported no significant changes in the brain glucose metabolism in patients with subtle cognitive impairment. 53 Overall, while neuroimaging studies on long COVID have provided significant and somewhat consistent results, there may be some concerns due to the heterogeneity of patients and self-reported ambiguous symptoms such as fatigue.…”

Section: Neuroimagingmentioning

confidence: 97%

“…Longitudinally, the long COVID metabolic pattern and cognitive dysfunction mostly improved in several months, but some residual abnormality remained 82 . Given that the brain glucose metabolism can be caused by astroglia as well as neuronal dysfunction, it can be speculated that astroglial inflammation may be involved in brain dysfunction in long COVID cases and could possibly lead to more severe sequelae such as neurodegenerative diseases 83 . On the other hand, another study reported no significant changes in the brain glucose metabolism in patients with subtle cognitive impairment 53 …”

Section: Examinations Of Long Covidmentioning

confidence: 99%

“… 93 In fact, brain PET in long COVID patients revealed hypometabolism, which is consistent with astroglial inflammation. 83 These factors may lead to neuropsychiatric symptoms in long COVID. Moreover, systemic inflammation of the blood vessels throughout the body may cause systemic symptoms of long COVID, which in turn may cause neuropsychiatric symptoms, such as insomnia, depression, and anxiety, as a secondary reaction.…”

Section: Potential Mechanism Of Long Covid and Its...mentioning

confidence: 99%

See 2 more Smart Citations

Neuropsychiatric aspects of long COVID: A comprehensive review

Kubota

Sone

2022

Psychiatry Clin Neurosci

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Although some patients have persistent symptoms or develop new symptoms following coronavirus disease 2019 (COVID-19) infection, neuropsychiatric aspects of long COVID are not well known. This review summarizes and provides an update on the neuropsychiatric dimensions of long COVID. Its neuropsychiatric manifestations commonly include fatigue, cognitive impairment, sleep disorders, depression, anxiety, and post-traumatic stress disorder. There are no specific tests for long COVID, but some characteristic findings such as hypometabolism on positron emission tomography have been reported. The possible mechanisms of long COVID include inflammation, ischemic effects, direct viral invasion, and social and environmental changes. Some patient characteristics and the severity and complications of acute COVID-19 infection may be associated with an increased risk of neuropsychiatric symptoms.Long COVID may resolve spontaneously or persist, depending on the type of neuropsychiatric symptoms. Although established treatments are lacking, various psychological and pharmacological treatments have been attempted. Vaccination against COVID-19 infection plays a key role in the prevention of long coronavirus disease. With differences among the SARS-CoV-2 variants, including the omicron variant, the aspects of long COVID are likely to change in the future. Further studies clarifying the aspects of long COVID to develop effective treatments are warranted.

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ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus

Yin

et al. 2023

Journal of Medical Virology

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Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea, and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potential to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virushost interaction, 68 Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory tract of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period was visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time perioddependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in the heart, liver, kidneys, lungs, and so on, but the liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days post inhalation, with brain and genitals still of a decreased SUV ACE2 ; meanwhile, kidneys were of an increased SUV ACE2 . These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was superior in an earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post-infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUV ACE2 and the ACE2 specificity were further confirmed. In conclusion, 68 Ga-cyc-DX600 was developed as an ACE2specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference and approach to explore the ACE2-related pathological basis of sequelae in long COVID.

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About the source and consequences of 18F-FDG brain PET hypometabolism in short and long COVID-19

Cited by 12 publications

References 15 publications

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Neuropsychiatric aspects of long COVID: A comprehensive review

ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus

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