Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) have been increasingly recognized. However, the pathophysiology of COVID-19 in the central nervous system remains unclear. Brain organoid models derived from human pluripotent stem cells are potentially useful for the study of complex physiological and pathological processes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as they recapitulate cellular heterogeneity and function of individual tissues. We identified brain organoid studies that provided insight into the neurotropic properties of SARS-CoV-2. While SARS-CoV-2 was able to infect neurons, the extent of neurotropism was relatively limited. Conversely, choroidal epithelial cells consistently showed a high susceptibility to SARS-CoV-2 infection. Brain organoid studies also elucidated potential mechanism for cellular entry, demonstrated viral replication, and highlighted downstream cellular effects of SARS-CoV-2 infection. Collectively, they suggest that the neuropsychiatric manifestations of COVID-19 may be contributed by both direct neuronal invasion and indirect consequences of neuroinflammation. The use of high throughput evaluation, patient-derived organoids, and advent of assembloids will provide a better understanding and functional characterization of the neuropsychiatric symptoms seen in post-acute COVID-19 syndrome. With advancement of organoid technology, brain organoids offer a promising tool for unravelling pathophysiologic clues and potential therapeutic options for neuropsychiatric complications of COVID-19.

Automated summary

Brain organoid models derived from human pluripotent stem cells provide valuable insights into the neurotropic properties of SARS-CoV-2. While neurons can be infected by SARS-CoV-2, the extent of neurotropism is limited compared to the high susceptibility of choroidal epithelial cells. These studies also shed light on the mechanisms of cellular entry, viral replication, and downstream effects of SARS-CoV-2 infection. The neuropsychiatric manifestations of COVID-19 may be a result of both direct neuronal invasion and indirect consequences of neuroinflammation.