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covid-19_and_central_nervous_system

COVID-19 and central nervous system

Evidence of the Distribution of ACE2 in the Human Brain

The brain has been reported to express ACE2 receptors that have been detected over glial cells and neurons, which makes them a potential target of COVID-19. Previous studies have shown the ability of SARSCoV to cause neuronal death in mice by invading the brain via the nose close to the olfactory epithelium 1).


It has been shown that similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in nervous tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COVID-19.

Most of the evidence of ACE2 expression in the brain comes from literature and mammalian tissue expression databases, 2) which prompted Baig et al. to investigate the neurotropic effects of SARSCoV-2 and its contribution toward the morbidity and mortality of patients with COVID-19.

Baig et al. investigated the density of the expression levels of ACE2 in the CNS, the host-virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. They also debated the need for a model for staging COVID-19 based on nervous tissue involvement 3).


The brain has been reported to express ACE2 receptors that have been detected over glial cells and neurons, which makes them a potential target of COVID-19. Previous studies have shown the ability of SARSCoV to cause neuronal death in mice by invading the brain via the nose close to the olfactory epithelium 4).

In the SARS-CoV infections that were reported in the past, autopsy findings of the patients have shown strong evidence of the presence of SARS-CoV by electron microscopy, immunohistochemistry, and real-time reverse transcriptional 5).

Patients with acute SARS-CoV illness have also demonstrated the presence of the virus in cerebrospinal fluid. The role of the blood-brain barrier in containing the virus and preventing it from gaining access to the neural tissues needs to be further explored in patients diagnosed with COVID-19. Recently, a study posted in medRxiv 6) has reported neurological manifestations in COVID-19 in the current outbreak that involved 214 patients, of which 78 (36.4%) patients had neurologic manifestations, which affirms our rationale of the neurotropic potential in the COVID-19 virus. Also, a finding published on a patient who had loss of involuntary control over breathing 7) during the recent outbreak with several other patients suffering acute respiratory failure implores healthcare professionals and clinicians to segregate COVID-19 patients into neurologically affected cases and those who are devoid of neurological deficits.


The dissemination of COVID-19 in the systemic circulation or across the cribriform plate of the ethmoid bone during an early or later phase of the infection can lead to cerebral involvement as has been reported in the past for SARS-CoV affected patients. The presence of the COVID-19 virus in the general circulation understandably enables it to pass into the cerebral circulation where the sluggish movement of the blood within the microcirculation could be one of the factors that may facilitate the interaction of the COVID-19 virus spike protein with ACE2 expressed in the capillary endothelium. Subsequent budding of the viral particles from the capillary endothelium and damage to the endothelial lining can favor viral access to the brain. Once within the milieu of the neuronal tissues, its interaction with ACE2 receptors expressed in neurons2 can initiate a cycle of viral budding accompanied by neuronal damage without substantial inflammation as has been seen with cases of SARS-CoV3 in the past. It is important to mention here that, long before the proposed anticipated neuronal damages occur, the endothelial ruptures in cerebral capillaries accompanied by bleeding within the cerebral tissue can have fatal consequences in patients with COVID-19 infections. The movement of the COVID-19 virus to the brain via the cribriform plate close to the olfactory bulb can be an additional pathway that could enable the virus to reach and affect the brain. Additionally, the findings like an altered sense of smell or hyposmia in an uncomplicated early stage COVID19 patient should be investigated thoroughly for CNS involvement.

1) , 4) , 5)
Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., and Perlman, S. (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 82 (15), 7264−75.
2)
Palasca, O., Santos, A., Stolte, C., Gorodkin, J., and Jensen, L. J. (2018) TISSUES 2.0: an integrative web resource on mammalian tissue expression. Database 2018, No. bay003.
3)
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020 Mar 13. doi: 10.1021/acschemneuro.0c00122. [Epub ahead of print] PubMed PMID: 32167747; PubMed Central PMCID: PMC7094171.
6)
Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Li, Y., Jin, H., and Hu, B.Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.02.22.20026500 (accessed on 2020-02-28).
7)
Li, Y. C., Bai, W. Z., and Hashikawa, T. (2020) The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J. Med. Virol., DOI: 10.1002/jmv.25728.
covid-19_and_central_nervous_system.txt · Last modified: 2020/04/03 13:09 by administrador