SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability

Fernanda Crunfli,Victor Corasolla Carregari,Flavio Protásio Veras,Pedro Henrique Vendramini,Aline Gazzola Fragnani Valença,André Saraiva Leão Marcelo Antunes,Caroline Brandão-Teles,Giuliana da Silva Zuccoli,Guilherme Reis-de-Oliveira,Lícia C.Silva-Costa,Verônica Monteiro Saia-Cereda,Ana Campos Codo,Pierina Lorencini Parise,Daniel A. Toledo-Teixeira,Gabriela Fabiano de Souza,Stéfanie Primon Muraro, Bruno Marcel Silva Melo,Glaucia M. Almeida,Egidi Mayara Silva Firmino,Isadora Marques Paiva,Bruna Manuella Souza Silva,Raíssa Guimarães Ludwig,Gabriel Palermo Ruiz,Thiago Leite Knittel,Gustavo Gastão Davanzo,Jaqueline Aline Gerhardt,Patrícia Brito Rodrigues,Julia Forato,Mariene Ribeiro Amorim, Natália Brunetti Silva,Matheus Cavalheiro Martini,Maíra Nilson Benatti,Sabrina Batah,Li Siyuan,Rafael Batista João,Lucas Scardua Silva,Mateus Henrique Nogueira,Ítalo Karmann Aventurato,Mariana Rabelo de Brito,Marina Alvim, José Roberto da Silva Júnior,Lívia Liviane Damião,Maria Ercilia de Paula Castilho Stefano,Iêda Maria Pereira de Sousa,Elessandra Dias da Rocha,Solange Maria Gonçalves,Luiz Henrique Lopes da Silva,Vanessa Bettini,Brunno de Campos,Guilherme Ludwing,Rosa Maria Mendes Viana,Ronaldo Martins,Andre Schwambach Vieira,José Carlos Alves-Filho,Eurico Arruda,Adriano Sebollela,Fernando Cendes,Fernando Cunha,André Ricardo de Lima Damásio,Marco Aurélio Ramirez Vinolo,Carolina Munhoz,Stevens K. Rehen,Thais Mauad,Amaro Duarte-Neto,Luiz Fernando Ferraz da Silva,Marisa Dolhnikoff,Paulo Saldiva,Alexandre Fabro,Alessandro S. Farias,Pedro Manoel M. Moraes-Vieira,José Luiz Proença Módena,Clarissa Yasuda,Marcelo A. Mori,Thiago Mattar Cunha,Daniel Martins de Souza

medRxiv(2020)

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摘要
Abstract 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.
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brain astrocytes,sars-cov
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