Molecular and cellular mechanisms of central nervous system alteration in COVID-19

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic dictates the need to study the molecular and cellular mechanisms of interaction between the pathogen and the human body. The manifestation of neurological symptoms in some patients with COVID-19 is a problem for neuroscientists due to the insufficiently understood pathomorphogenesis of the disease. This review systematizes the literature data reflecting the ways of penetration of SARS-CoV-2 into the brain, features of its interaction with neurons, neuroglia, and immune cells. It has been shown that the main mechanisms of SARS-CoV-2 neuroinvasion are presumably retrograde axonal transport along the fibers of the olfactory and vagus nerves; penetration through the damaged blood-brain barrier (BBB) or migration of immunocompetent cells containing viral particles through the intact BBB. It was found that virusinducible neuronal death is caused not only by a direct cytotoxic effect, but also due to dysregulation of the reninangiotensin system of the brain and the release of a large amount of inflammatory cytokines as a manifestation of a “cytokine storm”. The participation of neuroglial cells in the initiation and maintenance of neuroinflammatory and neurodegenerative processes due to the activation of their proinflammatory phenotype has been demonstrated. The role of mast cells in antiviral defense mechanisms and inflammatory reactions is discussed.