To the editor

We read with interest the review article by Adamczyk-Sowa et al1 on neurologic manifestations of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 It was concluded that clinicians should pay attention to neurologic signs and symptoms in COVID-19 that suggest the involvement of the central or peripheral nervous system caused by the infection.1 We have the following comments and concerns regarding this issue.

The authors claim that SARS-CoV-2 enters the cerebrospinal fluid (CSF) via olfactory epithelial cells and a trans-synaptic neural pathway in the olfactory bulb.1 However, in most patients undergoing a spinal tap (particularly those with suspected polyradiculitis or meningitis / encephalitis) and investigations of the CSF for SARS-CoV-2, tests for viral RNA yielded negative results in the CSF.2 Since the virus, nonetheless, has been found inside neurons, glial cells, and endothelial cells of the frontal lobe3 and in other cerebral locations, hematogenous spread appears to be more likely than neuronal dissemination. Damage to the blood-brain barrier (BBB) may occur from the vascular side of the BBB by a direct attack or indirect immunological attack of endothelial cells. Of note, SARS-CoV-2 not only exhibits high affinity to the angiotensin-converting enzyme 2 receptors of olfactory epithelial cells and taste buds but also to vascular endothelial cells.4 An argument against entry via the lymphatic system is that lymph node swelling is hardly reported in patients with COVID-19.

Neurologic signs and symptoms in addition to olfactory or gustatory disturbances, seizures, impaired consciousness, photophobia, hemiparesis, quadriparesis, facial weakness, aphasia, dysarthria, sensory disturbances, headache, and dizziness that should trigger the suspicion of neurologic involvement in COVID-19 include acute cognitive decline in the case of acute hemorrhagic necrotizing encephalitis (AHNE),5 ataxia in the case of cerebellitis, transverse syndrome due to transverse myelitis, spasticity, myoclonus, neurogenic dysphagia, dysexecutive syndrome, memory impairment, and psychosis.

Neurologic disease, in addition to meningitis / encephalitis, stroke, and epilepsy associated with COVID-19, include AHNE,5 cerebellitis, intracerebral bleeding, acute cerebral demyelination, vasculitis with endotheliitis of small or large cerebral arteries, acute disseminated encephalomyelitis, and posterior reversible encephalopathy syndrome.

Overall, the comprehensive review could benefit from a broader discussion about the hematogenous spread of the virus and dissemination to the brain as well as from considering other signs and symptoms and neurologic disorders as neurologic involvement in COVID-19.