Proteomics

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


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.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Cell Culture, Neuronal Stem Cell

DISEASE(S): Covid-19

SUBMITTER: Victor Corasolla Carregari  

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD023781 | Pride | 2022-09-01

REPOSITORIES: Pride

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Publications

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

Crunfli Fernanda F   Carregari Victor C VC   Veras Flavio P FP   Silva Lucas S LS   Nogueira Mateus Henrique MH   Antunes André Saraiva Leão Marcelo ASLM   Vendramini Pedro Henrique PH   Valença Aline Gazzola Fragnani AGF   Brandão-Teles Caroline C   Zuccoli Giuliana da Silva GDS   Reis-de-Oliveira Guilherme G   Silva-Costa Lícia C LC   Saia-Cereda Verônica Monteiro VM   Smith Bradley J BJ   Codo Ana Campos AC   de Souza Gabriela F GF   Muraro Stéfanie P SP   Parise Pierina Lorencini PL   Toledo-Teixeira Daniel A DA   Santos de Castro Ícaro Maia ÍM   Melo Bruno Marcel BM   Almeida Glaucia M GM   Firmino Egidi Mayara Silva EMS   Paiva Isadora Marques IM   Silva Bruna Manuella Souza BMS   Guimarães Rafaela Mano RM   Mendes Niele D ND   Ludwig Raíssa L RL   Ruiz Gabriel P GP   Knittel Thiago L TL   Davanzo Gustavo G GG   Gerhardt Jaqueline Aline JA   Rodrigues Patrícia Brito PB   Forato Julia J   Amorim Mariene Ribeiro MR   Brunetti Natália S NS   Martini Matheus Cavalheiro MC   Benatti Maíra Nilson MN   Batah Sabrina S SS   Siyuan Li L   João Rafael B RB   Aventurato Ítalo K ÍK   Rabelo de Brito Mariana M   Mendes Maria J MJ   da Costa Beatriz A BA   Alvim Marina K M MKM   da Silva Júnior José Roberto JR   Damião Lívia L LL   de Sousa Iêda Maria P IMP   da Rocha Elessandra D ED   Gonçalves Solange M SM   Lopes da Silva Luiz H LH   Bettini Vanessa V   Campos Brunno M BM   Ludwig Guilherme G   Tavares Lucas Alves LA   Pontelli Marjorie Cornejo MC   Viana Rosa Maria Mendes RMM   Martins Ronaldo B RB   Vieira Andre Schwambach AS   Alves-Filho José Carlos JC   Arruda Eurico E   Podolsky-Gondim Guilherme Gozzoli GG   Santos Marcelo Volpon MV   Neder Luciano L   Damasio André A   Rehen Stevens S   Vinolo Marco Aurélio Ramirez MAR   Munhoz Carolina Demarchi CD   Louzada-Junior Paulo P   Oliveira Renê Donizeti RD   Cunha Fernando Q FQ   Nakaya Helder I HI   Mauad Thais T   Duarte-Neto Amaro Nunes AN   Ferraz da Silva Luiz Fernando LF   Dolhnikoff Marisa M   Saldiva Paulo Hilario Nascimento PHN   Farias Alessandro S AS   Cendes Fernando F   Moraes-Vieira Pedro Manoel M PMM   Fabro Alexandre T AT   Sebollela Adriano A   Proença-Modena José L JL   Yasuda Clarissa L CL   Mori Marcelo A MA   Cunha Thiago M TM   Martins-de-Souza Daniel D  

Proceedings of the National Academy of Sciences of the United States of America 20220811 35


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  ...[more]

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