Potential mechanism of SARS‐CoV ‐2‐associated central and peripheral nervous system impairment

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is more than merely a respiratory disease, as it also presents with various neurological symptoms. SARS‐CoV‐2 may infect the central nervous system (CNS) and thus is neurotropic. However, the pathophysiological mechanism of coronavirus disease 2019 (COVID‐19)‐associated neuropathy remains unclear. Many studies have reported that SARS‐CoV‐2 enters the CNS through the hematogenous and neuronal routes, as well as through the main host neurological immune responses and cells involved in these responses. The neurological immune responses to COVID‐19 and potential mechanisms of the extensive neuroinflammation induced by SARS‐CoV‐2 have been investigated. Although CNS infection with SARS‐CoV‐2 was shown to lead to neuronal impairment, certain aspects of this mechanism remain controversial and require further analysis. In this review, we discussed the pathway and mechanisms of SARS‐CoV‐2 invasion in the CNS, and associated clinical manifestations, such as anosmia, headache, and hyposmia. Moreover, the mechanism of neurological damage caused by SARS‐CoV‐2 may provide potential treatment methods for patients presenting with SARS‐CoV‐2‐associated neuropathy.

Cerebral microvascular complications associated with SARS-CoV-2 infection: How did it occur and how should it be treated?

“…2 b). In the hematogenous route, viruses can spread into the circulatory system and then from there reach the brain and thus infect epithelial cells of the blood-cerebrospinal fluid barrier in the choroid plexus or ECs of the BBB [38] , [61] , [63] . The three important mechanisms, which have been proposed to describe the spread of the virus through the BBB, are the Trojan horse model, paracellular migration, and transcellular migration [64] .…”

New Daily Persistent Headache

“…23 There are many potential mechanisms by which headache may potentially be triggered by COVID-19 or other viral illnesses, leading to new daily persistent headache. 24,25 Direct neuronal entry of COVID-19 via the olfactory bulb has been observed and on a cellular level could occur via angiotensin-converting enzyme 2 host receptors, leading to trigeminovascular activation. Direct viral invasion remains plausible, and systemic inflammation with cytokine release may also contribute.…”

Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs

“…C-reactive protein (CRP), a non-specific marker of systemic inflammation, is induced by pro-inflammatory cytokines such as IL-6, and has been associated with chronic inflammation, and various degrees of cognitive dysfunction ( Watanabe et al, 2016 ; Luan and Yao, 2018 ; Vintimilla et al, 2019 ; Gupta et al, 2020b ; Xin et al, 2021 ). A cascade of events, referred to as “cytokine storm” or “cytokine release syndrome (CRS),” has been implicated in neurotoxicity, disruption of the integrity of BBB, neuroglial cells activation, and ultimately neuroinflammation ( Gupta et al, 2020b ; Zhang et al, 2022b ).…”