Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection

Mar Pacheco-Herrero; Luis O Soto-Rojas; Charles Harrington; Yazmin M.  Flores Martinez; Marcos M Villegas-Rojas; Alfredo M.  León-Aguilar; Paola A Martínez-Gómez; B. Berenice Campa-Córdoba; Ricardo Apátiga-Pérez; Carolin N.  Corniel-Taveras; Jesabelle de J.  Dominguez-García; Victor Manuel  Blanco-Alvarez; José Luna-Muñoz

doi:10.3389/fneur.2021.660087

Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection

Mar Pacheco-Herrero, Luis O Soto-Rojas, Charles Harrington, Yazmin M. Flores Martinez, Marcos M Villegas-Rojas, Alfredo M. León-Aguilar, Paola A Martínez-Gómez, B. Berenice Campa-Córdoba, Ricardo Apátiga-Pérez, Carolin N. Corniel-Taveras, Jesabelle de J. Dominguez-García, Victor Manuel Blanco-Alvarez, José Luna-Muñoz^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

Original language	English
Article number	660087
Number of pages	19
Journal	Frontiers in Neurology
Volume	12
Early online date	12 Apr 2021
DOIs	https://doi.org/10.3389/fneur.2021.660087
Publication status	Published - 12 Apr 2021

Keywords

SARS-CoV-2
storm cytokine syndrome
neuroinflammation
blood-brain barrier
neurological alterations
Alzheimer’s disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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© 2021 Pacheco-Herrero, Soto-Rojas, Harrington, Flores-Martinez, Villegas-Rojas, León-Aguilar, Martínez-Gómez, Campa-Córdoba, Apátiga-Pérez, Corniel-Taveras, Dominguez-García, Blanco-Alvarez and Luna-Muñoz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/
Final published version, 1.98 MBLicence: CC BY

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Pacheco-Herrero, M., Soto-Rojas, L. O., Harrington, C., Flores Martinez, Y. M., Villegas-Rojas, M. M., León-Aguilar, A. M., Martínez-Gómez, P. A., Campa-Córdoba, B. B., Apátiga-Pérez, R., Corniel-Taveras, C. N., Dominguez-García, J. D. J., Blanco-Alvarez, V. M., & Luna-Muñoz, J. (2021). Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection. Frontiers in Neurology, 12, [660087]. https://doi.org/10.3389/fneur.2021.660087

Pacheco-Herrero, M, Soto-Rojas, LO, Harrington, C, Flores Martinez, YM, Villegas-Rojas, MM, León-Aguilar, AM, Martínez-Gómez, PA, Campa-Córdoba, BB, Apátiga-Pérez, R, Corniel-Taveras, CN, Dominguez-García, JDJ, Blanco-Alvarez, VM & Luna-Muñoz, J 2021, 'Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection', Frontiers in Neurology, vol. 12, 660087. https://doi.org/10.3389/fneur.2021.660087

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title = "Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection",

abstract = "The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.",

keywords = "SARS-CoV-2, storm cytokine syndrome, neuroinflammation, blood-brain barrier, neurological alterations, Alzheimer{\textquoteright}s disease",

author = "Mar Pacheco-Herrero and Soto-Rojas, {Luis O} and Charles Harrington and {Flores Martinez}, {Yazmin M.} and Villegas-Rojas, {Marcos M} and Le{\'o}n-Aguilar, {Alfredo M.} and Mart{\'i}nez-G{\'o}mez, {Paola A} and Campa-C{\'o}rdoba, {B. Berenice} and Ricardo Ap{\'a}tiga-P{\'e}rez and Corniel-Taveras, {Carolin N.} and Dominguez-Garc{\'i}a, {Jesabelle de J.} and Blanco-Alvarez, {Victor Manuel} and Jos{\'e} Luna-Mu{\~n}oz",

note = "Acknowledgements We want to express our gratitude to the Union Medical University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer's disease and made our research possible. This work is dedicated to the memory of Professor Dr. Jos{\'e} Ra{\'u}l Mena L{\'o}pez†.",

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AU - Pacheco-Herrero, Mar

AU - Soto-Rojas, Luis O

AU - Harrington, Charles

AU - Flores Martinez, Yazmin M.

AU - Villegas-Rojas, Marcos M

AU - León-Aguilar, Alfredo M.

AU - Martínez-Gómez, Paola A

AU - Campa-Córdoba, B. Berenice

AU - Apátiga-Pérez, Ricardo

AU - Corniel-Taveras, Carolin N.

AU - Dominguez-García, Jesabelle de J.

AU - Blanco-Alvarez, Victor Manuel

AU - Luna-Muñoz, José

N1 - Acknowledgements We want to express our gratitude to the Union Medical University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer's disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López†.

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N2 - The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

AB - The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

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KW - storm cytokine syndrome

KW - neuroinflammation

KW - blood-brain barrier

KW - neurological alterations

KW - Alzheimer’s disease

U2 - 10.3389/fneur.2021.660087

DO - 10.3389/fneur.2021.660087

M3 - Article

C2 - 33912129

VL - 12

JO - Frontiers in Neurology

JF - Frontiers in Neurology

SN - 1664-2295

M1 - 660087

ER -

Elucidating the neuropathologic mechanisms of SARS-CoV-2 infection

Abstract

Keywords

UN SDGs

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