Infection Mechanism of SARS-COV-2 and Its Implication on the Nervous System

Abstract

In late December 2019, multiple atypical pneumonia cases resulted in severe acute respiratory syndrome caused by a pathogen identified as a novel coronavirus SARS-CoV-2. The most common coronavirus disease 2019 (COVID-19) symptoms are pneumonia, fever, dry cough, and fatigue. However, some neurological complications following SARS-CoV-2 infection include confusion, cerebrovascular diseases, ataxia, hypogeusia, hyposmia, neuralgia, and seizures. Indeed, a growing literature demonstrates that neurotropism is a common feature of coronaviruses; therefore, the infection mechanisms already described in other coronaviruses may also be applicable for SARS-CoV-2. Understanding the underlying pathogenetic mechanisms in the nervous system infection and the neurological involvement is essential to assess possible long-term neurological alteration of COVID-19. Here, we provide an overview of associated literature regarding possible routes of COVID-19 neuroinvasion, such as the trans-synapse-connected route in the olfactory pathway and peripheral nerve terminals and its neurological implications in the central nervous system.

Keywords: central nervous system; coronavirus disease 2019; long-term sequelae; neuroinvasion; neurological alterations; neurotropism; severe acute respiratory syndrome coronavirus 2.

Figure 1

Mechanisms of virion attachment/infection and possibles routes of SARS-CoV-2 neuroinvasiveness. SARS-CoV-2 spike protein interaction with the ACE-2 receptor may promote a direct host cell membrane fusion and the virion nucleocapsid release or induce a Furin/TMPRSS2-mediated endocytosis. Once in the epithelial cells, SARS-CoV-2 spreads to CNS through peripheral neurons in the olfactory epithelium and the second-order neurons along the olfactory nerve (Transcribial route). Similarly, the virus may use different peripheral nerves such as the vagus nerve, which afferences from the lungs and gut reach the brainstem. In the hematogenous route, the viremia induces the infection and viral transcytosis across vascular endothelial cells, as well as leukocytes infection and mobilization towards the BBB, and in several cases, the BBB disruption. CS, Cytokine storm.