Letter to the Editor: Is Coronavirus Disease 2019 A Real Threat to the Nervous System?

Since the first description of a patient with confirmed coronavirus disease 2019 whose cerebrospinal fluid (CSF) had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in early March 2020, an increasing amount of attention has been directly given to the neuroinvasive potential of SARS-CoV-2. Recently, Koralnik and Tyler systematically reviewed the neuroinvasion by SARS-CoV-2, the potential routes, and the pathophysiological mechanisms. We sincerely appreciate the immense achievement they reported; however, some problems regarding this topic require discussion.

First, although it has been commonly accepted that patients with SARS-CoV-2 infection can present with various neurological symptoms, including central nervous system symptoms (e.g., headache, seizure) and peripheral nervous system symptoms (e.g., anosmia, ageusia, myopathy), it is not certain that the neurological manifestations of coronavirus disease 2019 are truly neurologic in nature or constitute a systemic inflammatory response or common medical comorbidities. , Some neurological symptoms have been rather nonspecific because patients have often experienced headache and lose their sense of smell in many virus-induced respiratory infections. Likewise, previous studies have reported cerebrovascular events might have occurred in some cases of SARS-CoV-2 infection, which is more likely due to hypertension, considering the capabilities of SARS-CoV-2 to bind to angiotensin-converting enzyme 2.

In contrast, a previous report indicated that SARS-CoV-2 could have invaded the brainstem in very small number of patients, raising the question of whether invasion of brainstem contributed to the respiratory failure. However, to date, the answer remains unknown.

Finally, intracranial infection will always lead to encephalopathy, encephalitis, and meningitis, which could be confirmed through the tests of pathogens. However, the previous patient with positive findings in the CSF has been the only reported case; thus, the truth cannot yet be determined. Therefore, it is difficult to draw strong conclusions owing to the lack of evidence on neuropathy, such as gene sequences in the CSF and neurons, which require elucidation in further studies.