SARS-CoV-2-Mediated Neuropathogenesis, Deterioration of Hippocampal Neurogenesis and Dementia

Abstract

A significant portion of COVID-19 patients and survivors display marked clinical signs of neurocognitive impairments. SARS-CoV-2-mediated peripheral cytokine storm and its neurotropism appear to elicit the activation of glial cells in the brain proceeding to neuroinflammation. While adult neurogenesis has been identified as a key cellular basis of cognitive functions, neuroinflammation-induced aberrant neuroregenerative plasticity in the hippocampus has been implicated in progressive memory loss in ageing and brain disorders. Notably, recent histological studies of post-mortem human and experimental animal brains indicate that SARS-CoV-2 infection impairs neurogenic process in the hippocampus of the brain due to neuroinflammation. Considering the facts, this article describes the prominent neuropathogenic characteristics and neurocognitive impairments in COVID-19 and emphasizes a viewpoint that neuroinflammation-mediated deterioration of hippocampal neurogenesis could contribute to the onset and progression of dementia in COVID-19. Thus, it necessitates the unmet need for regenerative medicine for the effective management of neurocognitive deficits in COVID-19.

Keywords: COVID-19; cytokine storm; dementia; hippocampal neurogenesis; neuroinflammation.

Figure 1.

Schematic representation of the hippocampus in healthy vs COVID-19 condition in association with the respective cognitive status: The figure represents the neural stem cell-mediated neurogenic process in the hippocampus in healthy condition responsible for learning and memory and impaired neurogenesis in the hippocampus in COVID-19 state due to neuroinvasion of SARS-CoV-2 and neuroinflammation leading to dementia.