To the Editor:
Recently, we read with greatest interest the article by Wu et al (Wu et al., 2020), who reviewed the neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the possible mechanisms. We sincerely appreciate the immense achievement they make, however, some aspects of the neuroinvasive potential of SARS-CoV-2 still need to be discussed.
Like it was described for other human coronavirus, SARS-CoV-2 mainly invaded respiratory tract, which had already been demonstrated by previous clinical practice and pathological findings (Xu et al., 2020). Although there is widely accepted that human coronavirus, including SARS-CoV-1 that emerged in China in the late 2002, have neuroinvasive capacities based on both animal models and human studies, the properties of SARS-CoV-2 to invade and infect CNS remains controversial.
In general, virus with neuroinvasive potential could invade CNS cell though transneuronal route, or hematogenous route, or both, as a result of viral encephalitis and various neurological disorders, and the infection of CNS is finally confirmed by laboratory examinations (Desforges et al., 2014). In the early March 2020, medical workers from Beijing Didan Hospital reported the first case of coronavirus disease 2019 (COVID-19) with encephalitis whose cerebrospinal fluid (CSF) tested positive for SARS-CoV-2, raising the concern that SARS-CoV-2 might spread from respiratory tract to CNS. Since then, increasing number of attention are given to the neuroinvasive potential of SARS-CoV-2. However, to the best of our knowledge, it is currently the only case of SARS-CoV-2 infection with positive findings in CSF. A retrospective consecutive case series indicated 78 of 214 patients presented neurological symptoms, including central nervous system (CNS) symptoms (e. g. headache, dizziness), peripheral nervous system (PNS) impairments (e. g. taste impairment, smell impairment), and skeletal muscular injury (Mao et al., 2020).
It is difficult to draw strong conclusions since the CSF findings of 214 patients were not available, and it is unclear that whether these specific and nonspecific symptoms (e. g. headache) were a systemic inflammatory response or neurological disorders itself. Apart from symptoms, the evidence of neurological sign, particularly meningeal irrigation sign, is equally essential regarding the neurological manifestations of COVID-19, which was lack to date based on the reported studies. In this light, previous studies do not provide a valid evidence for the neuroinvasive potential of SARS-CoV-2, and much is left to be learned with thorough neurologic testing in large series with COVID-19 or animal models.
Despite of the controversy, we completely agree that the authors suggest caution when one patient with COVID-19 presents neurological symptoms and signs.
Funding
The current work has no funding.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.bbi.2020.05.079.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
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