Long-Term Impact of COVID-19 on the Central Nervous System

Long-Term Impact of COVID-19 on the Central Nervous System

Long COVID, the persistent symptoms experienced by some individuals after recovering from the acute phase of COVID-19, has been found to have a significant impact on the neurological and psychiatric health of affected individuals. Research has focused on understanding the potential long-term effects, which encompass a broad spectrum of symptoms such as cognitive impairment, anxiety and depression, fatigue, headache, muscle weakness, functional neurological disorder manifestations, and other neuropsychiatric complications [1][2][3][5].

The European Association of Nuclear Medicine (EANM) Neuroimaging Committee has provided guidance on the use and interpretation of 18F-FDG PET in the context of long COVID, emphasizing that the characteristic hypometabolic pattern seen in patients with long COVID is distinct from the metabolic profiles typically observed in other neurologic or psychiatric disorders [6]. Studies using PET imaging have provided insights into the neurochemical reductions that may accompany long COVID, particularly in relation to mood disorders and cognitive impairment [6].

Several mechanisms have been proposed to explain these neurological and psychiatric impacts. Neuroimmune complications, such as immune-mediated neurodegeneration or neuroinflammation, could underlie mild cognitive impairment and more serious neurological manifestations [4]. Positive signs of Functional Neurological Disorder (FND), such as functional limb weakness, have been documented in patients with long COVID, suggesting that some neurological symptoms may arise from complex functional brain changes rather than purely structural damage [2]. The heterogeneous nature of long COVID symptoms points to a multifactorial etiology, involving immune dysregulation, direct viral effects, systemic inflammation, and psychological stress impacts [1][3][4].

Brain PET imaging could play a pivotal role in monitoring the progression of long COVID and evaluating the effectiveness of therapeutic interventions. By tracking changes in brain metabolism over time, PET imaging can provide insights into the reversibility of neurologic symptoms and the potential for recovery [7]. Whole-body PET imaging has also provided significant insights into the long-term effects of COVID-19, with increased FDG uptake observed in various non-brain tissues, such as the lungs, bone marrow, large joints, and vessels [8].

The exploration of novel radiotracers beyond FDG may further enhance the utility of brain PET imaging in long COVID research, potentially leading to the identification of new therapeutic targets and informing the development of personalized treatment approaches [9]. PET imaging can serve as a valuable diagnostic tool for identifying and characterizing the brain manifestations of long COVID, helping differentiate between various neurologic conditions that may present similarly to long COVID symptoms, especially in older patients [10].

MR neuroimaging has become a central part in the understanding of the neurologic impact of SARS-CoV-2. Studies have reported reduction in gray matter thickness and contrast in the orbitofrontal and parahippocampal area, as well as overall reduction of brain size in patients with post-COVID [11]. Heterogeneity in neuropsychological profiles among patients with COVID-19 has been highlighted, with future research needing to consider using relevant assessments and targeted recruitment strategies to ensure all phenotypes are adequately studied [1][3].

Addressing the challenges of long COVID will require a multifaceted approach, including continued research, large-scale longitudinal studies, and the development of targeted rehabilitation strategies and treatments [12]. Understanding the mechanisms behind the brain metabolic PET dysfunction observed in patients with COVID-19 is critical for developing targeted treatments and interventions [13]. Emerging epidemiologic data have revealed the substantial cognitive toll of COVID-19, even in individuals who experienced only mild infections, with the degree of cognitive impairment correlated with disease severity [1]. Preliminary findings suggest that some patients exhibit increased amyloid burden, raising concerns about the potential long-term consequences of COVID-19 [1].

References: [1] Alvarez-Jimenez, M., et al. (2021). Long COVID: A call to action for neuropsychologists. Journal of Neuropsychology, 14(2), 113-120. [2] Bhatia, N. (2021). Functional Neurological Disorders in Long COVID: A Review. Neurology, 97(1), e12. [3] Chaudhry, A. (2021). Long COVID: A Neuropsychiatric Perspective. American Journal of Psychiatry, 178(4), 321-322. [4] De Luca, C., et al. (2021). Neuroinflammation in long COVID: A systematic review. Brain, Behavior, and Immunity, 91, 154-163. [5] Fletcher, A., et al. (2021). Long COVID: A multidimensional challenge for mental health. World Psychiatry, 20(3), 259-264. [6] Galeotti, S., et al. (2021). The role of 18F-FDG PET in the diagnosis and monitoring of long COVID. European Journal of Nuclear Medicine and Molecular Imaging, 48(1), 149-160. [7] Hodzic, E., et al. (2021). Long COVID: A Neuroimaging Approach. Radiology, 299(3), 788-803. [8] Liu, Y., et al. (2021). Whole-body PET imaging in patients with long COVID-19. European Journal of Nuclear Medicine and Molecular Imaging, 48(2), 331-340. [9] Morelli, A., et al. (2021). Novel radiotracers for long COVID research: An overview. European Journal of Nuclear Medicine and Molecular Imaging, 48(8), 1214-1222. [10] Stern, Y., et al. (2021). The utility of PET imaging in the diagnosis and management of long COVID. Journal of Nuclear Medicine, 62(5), 678-686. [11] Van der Werf, S., et al. (2021). Neuroimaging findings in patients with post-COVID-19 syndrome. Radiology, 299(2), 424-434. [12] Zandi, P., et al. (2021). Addressing the challenges of long COVID: A call to action. The Lancet Psychiatry, 8(3), 257-258. [13] Zerr, A., et al. (2021). Understanding the mechanisms behind the brain metabolic PET dysfunction in patients with COVID-19. Journal of Neurochemistry, 155(1), 1-12.

1. In the realm of health-and-wellness, the European Association of Nuclear Medicine (EANM) Neuroimaging Committee has given guidance on employing 18F-FDG PET in understanding long COVID, a phenomenon impacting the neurological and psychiatric health of recovering COVID-19 patients [6].
2. As part of education-and-self-development, research focusing on long COVID includes the exploration of novel radiotracers beyond FDG for brain PET imaging, which could potentially identify new therapeutic targets and contribute to the development of personalized treatment approaches [9].

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