؜⁨مراجعات PREreview لMorphological, cellular and molecular basis of brain infection in COVID-19 patients⁩ | ⁨PREreview⁩

الانتقال إلى تفاصيل المسودة البحثية الأولية الانتقال إلى مراجعات PREreview

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

Fernanda Crunfli وVictor Corasolla Carregari وFlavio Protasio Veras وPedro Henrique Vendramini وAline Gazzola Fragnani Valença وAndré Saraiva Leão Marcelo Antunes وCaroline Brandão-Teles وGiuliana da Silva Zuccoli وGuilherme Reis-de-Oliveira وLícia C. Silva-Costa وVerônica Monteiro Saia-Cereda وBradley Joseph Smith وAna Campos Codo وGabriela Fabiano de Souza وStéfanie Primon Muraro وPierina Lorencini Parise وDaniel A. Toledo-Teixeira وÍcaro Maia Santos de Castro وBruno Marcel Silva Melo وGlaucia M. Almeida وEgidi Mayara Silva Firmino وIsadora Marques Paiva وBruna Manuella Souza Silva وRafaela Mano Guimarães وNiele D. Mendes وRaíssa Guimarães Ludwig وGabriel Palermo Ruiz وThiago Leite Knittel وGustavo Gastão Davanzo وJaqueline Aline Gerhardt وPatrícia Brito Rodrigues وJulia Forato وMariene Ribeiro Amorim وNatália Brunetti Silva وMatheus Cavalheiro Martini وMaíra Nilson Benatti وSabrina Batah وLi Siyuan وRafael Batista João وLucas Scardua Silva وMateus Henrique Nogueira وÍtalo Karmann Aventurato وMariana Rabelo de Brito وMarina Koutsodontis Machado Alvim وJosé Roberto da Silva Júnior وLívia Liviane Damião وIêda Maria Pereira de Sousa وElessandra Dias da Rocha وSolange Maria Gonçalves وLuiz Henrique Lopes da Silva وVanessa Bettini وBrunno Machado de Campos وGuilherme Ludwig وLucas Alves Tavares وMarjorie Cornejo Pontelli وRosa Maria Mendes Viana وRonaldo Martins وAndre S. Vieira وJosé Carlos Alves-Filho وEurico Arruda وGuilherme Podolski-Gondim وMarcelo Volpon Santos وLuciano Neder وFernando Cendes وPaulo Louzada-Junior وRenê Donizeti Oliveira وFernando Queiroz Cunha وAndré Damásio وMarco Aurélio Ramirez Vinolo وCarolina Demarchi Munhoz وStevens K. Rehen وHelder I Nakaya وThais Mauad وAmaro Nunes Duarte-Neto وLuiz Fernando Ferraz da Silva وMarisa Dolhnikoff وPaulo Saldiva وAlessandro S. Farias وPedro Manoel M. Moraes-Vieira وAlexandre Todorovic Fabro وAdriano S. Sebollela وJosé Luiz Proença Módena وClarissa Lin Yasuda وMarcelo A. Mori وThiago Mattar Cunha وDaniel Martins-de-Souza

تاريخ النشر: 13 أكتوبر 2020
الخادم: medRxiv
DOI: 10.1101/2020.10.09.20207464

الملخص

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

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Ryan Salerno

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مراجعة PREreview بواسطة Ryan Salerno

من تأليف Ryan Salerno

Main Claim & Relevance:

This preprint brings forward several claims from different disciplines, all regarding potential long term effects of SARS-CoV-19 and their causes.
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اقرأ مراجعة PREreview التي أجراها Ryan Salerno