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

• DOI: 10.1101/2020.10.09.20207464
• Publication Date: 2020-10-13T22:45:34Z
• Authors: Fernanda Crunfli; Victor Corasolla ...; Flavio Protasio V...; Pedro Henrique Ve...; Aline Gazzola Fra...; André Saraiva Leã...; Caroline Brandão-...; Giuliana da Silva...; Guilherme Reis-de...; Lícia C. Silva-Costa; Verônica Monteiro...; Bradley Joseph Smith; Ana Campos Codo; Gabriela Fabiano ...; Stéfanie Primon M...; Pierina Lorencini...; Daniel A. Toledo-...; Ícaro Maia Santos...; Bruno Marcel Silv...; Glaucia M. Almeida; Egidi Mayara Silv...; Isadora Marques P...; Bruna Manuella So...; Rafaela Mano Guim...; Niele D. Mendes; Raíssa Guimarães ...; Gabriel Palermo Ruiz; Thiago Leite Knittel; Gustavo Gastão Da...; Jaqueline Aline G...; Patrícia Brito Ro...; Julia Forato; Mariene Ribeiro A...; Natália Brunetti ...; Matheus Cavalheir...; Maíra Nilson Benatti; Sabrina Batah; Li Siyuan; Rafael Batista João; Lucas Scardua Silva; Mateus Henrique N...; Ítalo Karmann Ave...; Mariana Rabelo de...; Marina Koutsodont...; José Roberto da S...; Lívia Liviane Damião; Iêda Maria Pereir...; Elessandra Dias d...; Solange Maria Gon...; Luiz Henrique Lop...; Vanessa Bettini; Brunno Machado de...; Guilherme Ludwig; Lucas Alves Tavares; Marjorie Cornejo ...; Rosa Maria Mendes...; Ronaldo Martins; Andre S. Vieira; José Carlos Alves...; Eurico Arruda; Guilherme Podolsk...; Marcelo Volpon Sa...; Luciano Neder; Fernando Cendes; Paulo Louzada-Junior; Renê Donizeti Oli...; Fernando Queiroz ...; André Damásio; Marco Aurélio Ram...; Carolina Demarchi...; Stevens K. Rehen; Helder I Nakaya; Thais Mauad; Amaro Nunes Duart...; Luiz Fernando Fer...; Marisa Dolhnikoff; Paulo Saldiva; Alessandro S. Farias; Pedro Manoel M. M...; Alexandre Todorov...; Adriano S. Sebollela; José Luiz Proença...; Clarissa Lin Yasuda; Marcelo A. Mori; Thiago Mattar Cunha; Daniel Martins-de...
• Keywords: Hypermetabolism; Anosmia; Orbitofrontal cortex; Neurocognitive

Abstract Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, the long-term dysfunction has been frequently observed after mild infection. Here we show spectrum of cerebral impact SARS-CoV-2 infection ranging from alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to acute damage confirmed brain tissue samples extracted orbitofrontal region (via endonasal trans-ethmoidal approach) who died COVID-19. We used surface-based analyses 3T MRI identified atrophy a group 81 patients (77% referred anosmia or dysgeusia during stage) compared 145 healthy volunteers; this correlated symptoms cognitive dysfunction. In an independent cohort 26 COVID-19, histopathological signs as guide for possible found that among 5 exhibited those signs, all them had genetic material virus brain. Brain these also foci replication, particularly astrocytes. Supporting hypothesis astrocyte neural stem cell-derived human astrocytes vitro are susceptible through non-canonical mechanism involves spike-NRP1 interaction. SARS-CoV-2-infected manifested changes energy metabolism key proteins metabolites fuel neurons, well biogenesis neurotransmitters. Moreover, elicits secretory phenotype reduces neuronal viability. Our data support model which reaches brain, infects consequently leads death These deregulated processes likely contribute structural functional seen brains patients.