The Immunopathogenesis of Neuroinvasive Lesions of SARS-CoV-2 Infection in COVID-19 Patients

Abstract

The new coronavirus disease COVID-19 was identified in December 2019. It subsequently spread across the world with over 125 M reported cases and 2.75 M deaths in 190 countries. COVID-19 causes severe respiratory distress; however, recent studies have reported neurological consequences of infection by the COVID-19 virus SARS-CoV-2 even in subjects with mild infection and no initial neurological effects. It is likely that the virus uses the olfactory nerve to reach the CNS and that this transport mechanism enables virus access to areas of the brain stem that regulates respiratory rhythm and may even trigger cell death by alteration of these neuronal nuclei. In addition, the long-term neuronal effects of COVID-19 suggest a role for SARS-CoV-2 in the development or progression of neurodegerative disease as a result of inflammation and/or hypercoagulation. In this review recent findings on the mechanism(s) by which SARS-CoV-2 accesses the CNS and induces neurological dysregulation are summarized.

Keywords: COVID-19; IL-6; SARS-CoV-2-; cytokine storm; neuroinvasive lesions.

Figure 1

The possible mechanisms of virus entry to CNS and brain injury during SARS-Cov2 infection. SARS-Cov2 can reach the central nervous system (CNS) by retrograde transmission along the peripheral nervous system; by activation of the neuropilin-1 (NRP1) receptor; via the systemic circulation and disruption of the BBB. Viral infection can cause aggregation α-synuclein and trigger α-synucleinopthies. Viral replication triggers cytokine storm and case to vascular leakage and BBB disruption. Virus infection may trigger brain hypoxia during which hypoxia inducible factor 1 (HIF-1α) is activated in the brain and promotes the production of IL-6 TNF-α and M1 MQ polarization at the site of infection. Hypxia in the brain impairs metabolic pathways and further promotes neurodegeneration and brain injury.