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.

Plasma markers of neurologic injury and systemic inflammation in individuals with self-reported neurologic post-acute sequelae of SARS-CoV-2 infection (PASC)

“…These include direct viral infection, systemic inflammation, compartmentalized neuroinflammation, and sequelae of thrombotic injury. Viral tropism for human astrocytes has been demonstrated in-vivo, 54 post-mortem brain samples from COVID-19 patients have shown preferential infection of astrocytes, 55 and a case-control study of brain samples uncovered altered gene expression in some astrocytes. 56 Astrocyte dysfunction could relate to emerging cognitive PASC complaints, which can encapsulate attention and working memory deficits.…”

Neurogenesis and Viral Infection

“…The recent development of cortical organoids containing pericyte-like cells (PLCs), allowed the researchers to demonstrate that PLCs can serve as SARS-CoV-2 ‘replication hubs’, sustaining viral invasion and spread to neighboring cells, including astrocytes ( 85 ). Indeed, a neuropathological study of post-mortem brain of COVID-19 patients found that astrocytes are the major site of SARS-CoV-2 infection and replication ( 86 ).…”

Anticoronavirus and Immunomodulatory Phenolic Compounds: Opportunities and Pharmacotherapeutic Perspectives

“…Neurologic symptoms have been described in COVID-19 patients, including anosmia, ageusia, encephalopathy, seizures, encephalitis, stroke, and cognitive disturbance [188,189]. SARS-CoV-2 have been shown to infect neurons and damage the central nervous system (CNS) [190,191]. The detection of low or no viral copies in the brain tissue has been described in a number of COVID-19 cases with neurologic complications [192], and it remains unclear whether the CNS complications are caused by direct infection or inflammation.…”