Authors’ reply

We would like to thank Dr. Finsterer and Dr. Scorza for their interest in our article and important comments.

We agree with the observation that the hematogenous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seems to be the first route of viral dissemination in the host organism, considering the multiplicity of organs affected during infection. Some reports have suggested that the virus may enter the central nervous system via endothelial cell infection of the blood-brain barrier or through infected monocytes or macrophages.1 On the other hand, in view of the fact that neurologic symptoms, especially loss of smell and taste, very often precede all other symptoms or are even the only symptoms that occur, it is reasonable to anticipate neuronal retrograde dissemination. Indeed, in some reports, the presence of SARS-CoV-2 RNA has been shown in both oropharyngeal swab and cerebrospinal fluid specimens.2,3 In our opinion, it is impossible to dissect the clinical relevance of those routes as well as a potential for others.

Certainly, the list of neurologic disorders that are associated with SARS-CoV-2 infection or could potentially be its sequelae will become much longer with new knowledge. Up to date, many of the suggested diseases and / or manifestations are based on case reports and it is crucial to consider them, but it is difficult to draw conclusions on their relevance in coronavirus disease 2019 (COVID-19). What adds to the complexity of the issue, neurologic involvement during SARS-CoV-2 infection results not only from the direct effect of the virus, but, in our opinion more importantly, should potentially be linked to defective immune activation and inflammation.4 Finally, some disorders described, such as posterior reversible encephalopathy syndrome, could not be directly related to SARS-CoV-2 infection yet to its treatment, ie, the use of potentially neurotoxic off-label therapies or prolonged intensive care unit treatment.5 On one hand, neural complications are among the most important complications of SARS-CoV-2 infection. On the other hand, reports on a specific disease should be treated with caution, as there have been only few of them and they need to be validated in large prospective datasets.

The aim of our review was to draw clinicians’ attention to various neurologic symptoms that may be caused by SARS-CoV-2 yet not primarily being of neurologic origin. This may contribute to a faster diagnosis and treatment of COVID-19.