Astroglia-mediated neuroinflammation as a putative mechanism of neurological outcomes in COVID-19? Insights from a Brazilian cohort.

NeuroCOVID-19 has emerged as a significant global health concern, presenting a wide spectrum of neurological manifestations, including headaches, brain fog and anosmia. While mounting evidence indicates that SARS-CoV-2 infection compromises central nervous system (CNS) function, the precise processes underlying these effects remain incompletely understood. Although neurons have been extensively studied, astrocytes - critical regulators of brain homeostasis - have been largely overlooked in this context. In this study, we position astrocytes as central players in the neuropathological landscape of neuroCOVID-19, challenging their traditionally supportive role. We evaluated the frequent neurological symptoms in a Brazilian cohort of COVID-19 patients and investigated whether SARS-CoV-2 infection of cortical astrocytes induces neuroinflammation, glutamatergic imbalance, vasoregulatory disruption, and apoptosis as likely pathogenic processes. Among 162 COVID-19-positive patients, headache (53.09 %), brain fog (42.15 %), and anosmia (38.72 %) were the most commonly reported symptoms. Using human-induced pluripotent stem cell (hiPSC)-derived astrocytes, we found that SARS-CoV-2 infection promotes a pronounced pro-inflammatory response, evidenced by elevated levels of IL-6, IL-15, and IL-4 in the culture supernatant. Infected astrocytes also showed reduced mRNA expression of