This narrative review from JAMA Neurology summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis.
Emerging data suggest that ACE2 receptors are expressed in multiple regions of the human and mouse brain, including the motor cortex, posterior cingulate cortex, ventricles, substantia nigra, olfactory bulb, middle temporal gyrus, ventrolateral medulla, nucleus of tractus solitarius, and dorsal motor nucleus of the vagus nerve (A) and on several key cell types that make up the central nervous system, including neurons, microglia, astrocytes, and oligodendrocytes (B).35-37 C, ACE2 receptors on a medullary neuron binding to the SPIKE protein on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [Ref: Zubair AS, et al. JAMA Neurol. 2020;77(8):1018–1027]
A, Coronavirus (CoV) has been shown to spread via the transcribrial route from the olfactory epithelium along the olfactory nerve to the olfactory bulb within the central nervous system. B, CoV has been shown to spread retrograde via transsynaptic transfer using an endocytosis or exocytosis mechanism and a fast axonal transport (FAT) mechanism of vesicle transport to move virus along microtubules back to neuronal cell bodies.
A, Infected vascular endothelial cells have been shown to spread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to glial cells in the central nervous system. B, Known as the Trojan horse mechanism, infected leukocytes can cross the blood-brain barrier to infect the central nervous system. CoV indicates coronavirus
Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol. 2020;77(8):1018–1027. doi:10.1001/jamaneurol.2020.2065