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Review
. 2020 Oct 30;20(12):60.
doi: 10.1007/s11910-020-01079-7.

Central Nervous System Manifestations Associated with COVID-19

Afshin A Divani  1 , Sasan Andalib  2   3   4 , José Biller  5 , Mario Di Napoli  6 , Narges Moghimi  2 , Clio A Rubinos  7 , Christa O'Hana Nobleza  8 , P N Sylaja  9 , Michel Toledano  10 , Simona Lattanzi  11 , Louise D McCullough  12 , Salvador Cruz-Flores  13 , Michel Torbey  2 , M Reza Azarpazhooh  14
Affiliations
Review

Central Nervous System Manifestations Associated with COVID-19

Afshin A Divani et al. Curr Neurol Neurosci Rep. .

Erratum in

  • Correction to: Central Nervous System Manifestations Associated with COVID-19.
    Divani AA, Andalib S, Biller J, Di Napoli M, Moghimi N, Rubinos CA, O'Hana Nobleza C, Sylaja PN, Toledano M, Lattanzi S, McCullough LD, Cruz-Flores S, Torbey M, Azarpazhooh MR. Divani AA, et al. Curr Neurol Neurosci Rep. 2020 Nov 12;20(12):66. doi: 10.1007/s11910-020-01086-8. Curr Neurol Neurosci Rep. 2020. PMID: 33184674 Free PMC article.

Abstract

Purpose of review: Coronavirus disease 2019 (COVID-19) has become a global health crisis of our time. The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization. COVID-19 has a wide range of respiratory symptoms from mild to severe and affects several other organs, increasing the complexity of the treatment. There is accumulating evidence to suggest that SARS-CoV-2 can target the nervous system. In this review, we provide an account of the COVID-19 central nervous system (CNS) manifestations.

Recent findings: A broad spectrum of the CNS manifestations including headache, impaired consciousness, delirium, loss of smell and taste, encephalitis, seizures, strokes, myelitis, acute disseminated encephalomyelitis, neurogenic respiratory failure, encephalopathy, silent hypoxemia, generalized myoclonus, neuroleptic malignant syndrome and Kawasaki syndrome has been reported in patients with COVID-19. CNS manifestations associated with COVID-19 should be considered in clinical practice. There is a need for modification of current protocols and standing orders to provide better care for COVID-19 patients presenting with neurological symptoms.

Keywords: CNS manifestations; COVID-19; Neurological manifestations; Pandemic; SARS-CoV-2; Stroke.

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Conflict of interest statement

Afshin A. Divani, Sasan Andalib, José Biller, Mario Di Napoli, Narges Moghimi, Clio A. Rubinos, Christa O’Hana Nobleza, P.N Sylaja, Michel Toledano, Simona Lattanzi, Louise D McCullough, Salvador Cruz-Flores, Michel Torbey, and M. Reza Azarpazhooh each declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic process of the SARS-CoV-2’s internalization, proliferation in the cell, and influence on RAS. Endocytosis of SARS-CoV-2 occurs when the viral S glycoprotein binds to ACE2, with the help of TMPRSS2 and Cat B and Cat L. Viral gene expression is done in the nucleus. SARS-CoV-2 causes mitochondrial dysfunction and downregulates ACE2, which in turn under-activates the RAS alternative pathway (ACE2-Ang-(1-7)-Mas). Consequently, under-activation of the alternative axis brings about over-activation of the classical RAS pathway (ACE-Ang II-AT1R). The resultant imbalance in neuroinflammation, oxidative stress, thrombotic response, and vasodilation can be involved in the pathophysiology of CNS manifestations associated with COVID-19. Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2, RAS: renin-angiotensin system, ACE2: angiotensin-converting enzyme 2, TMPRSS2: Transmembrane protease, serine 2, Cat B: Cathepsin B, Cat L: Cathepsin L, Ang: angiotensin, Mas: Mas receptor, AT1R: angiotensin 1 receptor
See this image and copyright information in PMC

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