April 20, 2020 by Sam Bazzi
In this week’s neurology blog, I would like to highlight a review published in Neurology Clinical Practice, in which Dr. Carlos A. Pérez from the University of Texas Health Science Center at Houston, outlines some of the newly appreciated neurologic complications of COVID-19.
Currently, it is thought that neurological complications of COVID-19 result in part from indirect actions of SARS-CoV-2 on peripheral organs. For example, injury to the lungs, kidneys, liver, and heart could result in dysregulation of homeostasis and indirectly lead to neurological signs (eg uremia could lead to altered mental status.) In particular, the “cytokine storm,” hypercoagulability and direct myocardial invasion by SARS-CoV-2 could increase the risk of cardiac failure and arrhythmias, which could in turn increase the risk of stroke (Pérez, 2020).
What is also very interesting, but less understood, is the potential mechanism of direct neurologic damage by SARS-CoV-2. Like the previous SARS virus (SARS-CoV), SARS-CoV-2 can enter human host cells by binding to angiotensin-converting enzyme 2 (ACE2) receptor. While the exact mechanism of CNS injury is not established, SARS-CoV is known to enter the CNS and many neurons express ACE2 receptor, suggesting a potential target for injury. An alternative route into the CNS is via the olfactory bulb, as shown in experimental animal models (Netland, et al., 2020). Via this route, SARS-CoV-2 could lead to direct neuronal injury within different brain regions, including the brainstem cardiorespiratory centers, which could account for the cardiovascular/respiratory complications observed in COVID-19 patients. ACE2 receptors have also been shown to be expressed in microvillar cells and Bowman’s gland cells within the nasal passages, though it is unknown whether SARS-CoV-2 actually enters these cells (Gupta, et al., 2020). Nevertheless, it is possible that the observed dysfunction within the gustatory and olfactory systems, ie lack of smell (anosmia) and lack of taste (ageusia), may be due to direct viral invasion and damage to the olfactory system. Alternatively, these neurological symptoms may be due to a secondary inflammatory process within the nasal mucosa.
Lastly, Dr. Perez’ review covered post-infectious neurologic complications. Dr. Pérez suggested that the “presence and persistence of human coronaviruses within the CNS may lead to misdirected host immune responses, which may lead to autoimmune inflammatory and demyelinating syndromes in some people.” (Pérez, 2020).
Written by: Sam Bazzi
Edited by: Jina Zhou and Esther Melamed
4/20/2020
References
Gupta, K., Mohanty, S. K., Kalra, S., Mittal, A., Mishra, T., Ahuja, J., … & Ahuja, G. (2020). The molecular basis of loss of smell in 2019-nCoV infected individuals.
Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., & Perlman, S. (2008). Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. Journal of virology, 82(15), 7264–7275. https://doi.org/10.1128/JVI.00737-08
Pérez, C. A. (2020). Looking ahead: The risk of neurologic complications due to COVID-19. Neurology: Clinical Practice.
Talbot, P. J., Paquette, J. S., Ciurli, C., Antel, J. P., & Ouellet, F. (1996). Myelin basic protein and human coronavirus 229E cross‐reactive T cells in multiple sclerosis. Annals of neurology, 39(2), 233-240.
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