Neuromechanisms of SARS-CoV-2: A Review

Abstract

Recent studies have suggested the neuroinvasive potential of severe acute respiratory coronavirus 2 (SARS-CoV-2). Notably, neuroinvasiveness might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). Some studies have demonstrated that synapse-connected routes may enable coronaviruses to access the central nervous system (CNS). However, evidence related to the presence of SARS-CoV-2 in the CNS, its direct impact on the CNS, and the contribution to symptoms suffered, remain sparse. Here, we review the current literature that indicates that SARS-CoV-2 can invade the nervous system. We also describe the neural circuits that are potentially affected by the virus and their possible role in the progress of COVID-19. In addition, we propose several strategies to understand, diagnose, and treat the neurological symptoms of COVID-19.

Keywords: COVID-19; SARS-CoV-2; anosmia; central nervous system; dysgeusia; peripheral nervous system.

Figure 1

Diagram illustrating the cell types found in the olfactory bulb and part of the olfactory pathway. (A) OB, olfactory bulb; OT, olfactory tract; ONF, olfactory nerve fibers; CP, cribiform plate of ethmoid bone. (B) ONF, olfactory nerve fibers; CP, cribiform plate of ethmoid bone.; LP, lamina propria; OE, olfactory epithelium; BC, basal cells; SC, supporting (sustentacular) cells; OBG, olfactory Bowman's gland; ORC, olfactory receptor cells; Kn, olfactory Knobs; OC, olfactory cilia.

Figure 2

Diagram illustrating the main connections of the primary olfactory cortex. Viral sketches represent the possible symptoms related to the area of impairment: Loss of smell is probably the most evident symptom (1 and 2). However, through direct and indirect connections, the olfactory pathway may be related to several neurologic symptoms. For instance, the connections of the olfactory pathway with the amygdala nuclei may be related to emotional impairment. In addition, other central nervous system changes and neurologic symptoms that may be related to direct or indirect connections of the olfactory pathway are illustrated in this figure. For example, indirect connections to some hypothalamic nuclei, especially the supraoptic nucleus (3) may affect neuroendocrine control, which may, in turn, affect the function of the pituitary gland (4). Moreover, connections to the hippocampus (5) may result in memory impairment. On the other hand, indirect connections to some thalamic nuclei may be associated with sensory and movement impairment (6) while the connections to the frontal and insular cortices (7) may be associated with cognitive impairment. Indirect connections with the brainstem may also result in autonomic nervous system impairment (8). Not surprisingly, the ACE receptor has been found in several of the areas illustrated in this figure (Chen R. et al., 2020). This figure has been adapted from a previous work Devere (2017).