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Grant number: 22/11740-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2023
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Clarissa Lin Yasuda
Grantee:Thierry Kaue Alves Silva Souza
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID


COVID-19 is a disease caused by the SARS-CoV-2 virus. It has been strongly linked withneurological, neurodegenerative, and neuropsychiatric disorders, involving both Central(vertigo, headache, epileptic seizures, ataxia) and peripheral (neuropathic pain, hyposmia,dysgeusia) Nervous Systems. Moreover, it is estimated that around 50% of patients infectedwith SARS-CoV-2, regardless of the severity of symptoms of the infection, will develop a post-acute syndrome known as long-term Covid syndrome, which includes fatigue.Currently, fatigue is predominantly understood as an emotion, part of a complex network ofchemical mediators that signal and respond to stimuli and stress in the organism. THe centralnervous system works to ensure the control and regulation of homeostasis and the organismto avoid damage to the body. Chronic fatigue syndrome (CFS) is a disease characterized bydebilitating fatigue for longer than 6 months, associated with myalgias, headaches, sleepdisorders, and cognitive impairment. Although CFS is a disease with multiple factors andcomplex mechanisms, there were multiple studies that linked it with neuroendocrine disordersand other diseases associated with central nervous system disorders, including mastocytosisand mastoid cell activation syndrome.Recent publications have also related the infection of pregnant women with SARS-CoV-2 withthe increase in the incidence of preeclampsia, a complication characterized by high levels ofcorticotropin-releasing factor, a hormone secreted by the hypothalamus, especially understress. In many cases, patients with CFS report the onset of symptoms after a significantstressor, usually a viral infection, and tend to increase in intensity during the presence ofphysical and psychological stressors; in stressful situations, one of the main hormonesproduced by the body is a corticotropin-releasing factor. Another factor that leads us tobelieve in an association between CFS and the hypothalamic-pituitary-adrenal (HPA) axis isthat the main symptoms of CFS (pain, fatigue, depression) are also present in patients inwithdrawal from hypercortisolism states.Several studies have already linked changes in the HPA axis with patients with CFS, withcommon findings being the reduction of cortisol production. Recent studies havedemonstrated a correlation between fatigue and volumetric alterations of the caudate nucleusand the putamen and between fatigue and alterations in working memory.A correlation was also found between Sars-Cov-2 virus infection and fatigue, cognitivedifficulties, worse global cognition, and worse executive functions compared to controls, inaddition to an evident impairment in sustained and executive attention. Higher resting motorthresholds, lower motor evoked potential amplitudes, and longer cortical silence periods werealso detected, besides long-range intracortical inhibition and short-latency afferent inhibitionwere also impaired, which indicates an alteration in GABA-ergic and cholinergicneurotransmission.This study aims to understand the relationship between fatigue and cortical and subcorticalstructures, which can help to clarify the mechanisms by which the virus acts and eventuallyprovide targets for specific treatments that could alleviate the symptoms.

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