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

Crunfli, F.; Corasolla Carregari, V.; Veras, F. P.; Vendramini, P. H.; Valenca, A. G. F.; Antunes, A. S. L. M.; Brandao-Teles, C.; Zuccoli, G. d. S.; Reis-de-Oliveira, G.; Silva-Costa, L. C.; Saia-Cereda, V. M.; Codo, A. C.; Parise, P. L.; Toledo-Teixeira, D. A.; de Souza, G. F.; Muraro, S. P.; Melo, B. M. S.; Almeida, G. M.; Firmino, E. M. S.; Ludwig, R. G.; Palermo Ruiz, G.; Knittel, T. L.; Davanzo, G. G.; Gerhardt, J. A.; Rodrigues, P. B.; Forato, J.; Amorim, M. R.; Brunetti Silva, N.; Martini, M. C.; Benatti, M. N.; Batah, S.; Siyuan, L.; Pereira Silva, R. E. M.; Joao, R. B.; Silva, Scardua

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.