COVID-19 patients may exhibit neuropsychiatric and/or neurological symptoms. We found that anxiety and cognitive impairment are manifested by 28-56% of SARS-CoV-2-infected individuals with mild or no respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 19% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection, particularly in astrocytes. Infection of neural stem cell-derived astrocytes changed energy metabolism, altered key proteins and metabolites used to fuel neurons and for biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients.

COVID-19 patients may exhibit neuropsychiatric and neurological symptoms. We found that anxiety and cognitive impairment are manifested by 28-56% of SARS-CoV-2-infected individuals with mild respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 25% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Infection of neural stem cell-derived astrocytes changed energy metabolism, altered key proteins and metabolites used to fuel neurons and for biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients.

No abstract

A Esclerose Múltipla é uma doença autoimune crônica e desmielinizante, que envolte fatores genéticos e ambientais. Acredita-se que dentre esses fatores está a deficiência de Vitamina D3. Anteriormente, nós demonstramos que as células dendríticas (DCs) são o principal alvo de regulação da vitamina, induzindo um perfil tolerogênico das DCs dependente da expressão de IDO. Essas DCs IDO+ induzem o aumento e a estimulação de linfócitos T CD4+FOXP3+ com ação reguladora, diminuido a resposta inflamatória no modelo experimental (EAE). A IDO gera quinureninas, que serão reconhecidas pelo receptor aril hidrocarboneto (AhR) gerando uma resposta imunossupressora. Assim, nosso objetivo foi verificar a participação dos produtos da IDO expressa por células dendríticas tolerogênicas, geradas na presença da vitamina D3, na indução de células T regulatórias.