SARS-CoV-2 potential pathways of neuroinvasion and the role of astrocytes in neuroinvasion

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well characterized by its respiratory infection and associated respiratory complications. However, increasing evidence has shown that the virus can affect other organ systems besides the lungs such as the brain. Disease manifestations in infected patients such as encephalitis, psychosis, cerebrovascular injury, fatigue, loss of taste, and loss of smell have been reported in over one-third of hospitalized COVID-19 patients. Moreover, MRI-based screenings have shown structural damage to the brain of patients recovering from COVID-19. Despite these reported complications, there have been few studies that have examined the neurotropism of SARS-CoV-2 and the cause of these neurological complications. One suggested cause is direct neural infection also known as neuroinvasion. Recent studies using human brain organoids and mouse models have shown the neuroinvasive capacity of SARS-CoV-2 and its ability to directly infect neurons. However, the specific mechanism by which the virus enters the central nervous system and causes damage to neurons is unknown. Furthermore, for the virus to invade the brain it must bypass the blood brain barrier. Astrocytes play a key role in the maintenance of the blood brain barrier but their involvement in SARS-CoV-2 neuroinvasion has not been fully explored. This article will examine the neurotropism of SARS-CoV-2, focusing on the potential pathways SARS-CoV-2 uses to enter neurons in the brain and what role astrocytes play in neuroinvasion. Answering these questions could provide novel insight into new potential pathways and mechanisms that may be critical for disease prevention, developing therapeutics, and understanding the long-term complications of COVID-19 also known as long COVID.