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SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury

Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe p...

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Autores principales: Fenrich, Matija, Mrdenovic, Stefan, Balog, Marta, Tomic, Svetlana, Zjalic, Milorad, Roncevic, Alen, Mandic, Dario, Debeljak, Zeljko, Heffer, Marija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419602/
https://www.ncbi.nlm.nih.gov/pubmed/32848621
http://dx.doi.org/10.3389/fncel.2020.00229
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author Fenrich, Matija
Mrdenovic, Stefan
Balog, Marta
Tomic, Svetlana
Zjalic, Milorad
Roncevic, Alen
Mandic, Dario
Debeljak, Zeljko
Heffer, Marija
author_facet Fenrich, Matija
Mrdenovic, Stefan
Balog, Marta
Tomic, Svetlana
Zjalic, Milorad
Roncevic, Alen
Mandic, Dario
Debeljak, Zeljko
Heffer, Marija
author_sort Fenrich, Matija
collection PubMed
description Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.
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spelling pubmed-74196022020-08-25 SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury Fenrich, Matija Mrdenovic, Stefan Balog, Marta Tomic, Svetlana Zjalic, Milorad Roncevic, Alen Mandic, Dario Debeljak, Zeljko Heffer, Marija Front Cell Neurosci Neuroscience Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research. Frontiers Media S.A. 2020-08-05 /pmc/articles/PMC7419602/ /pubmed/32848621 http://dx.doi.org/10.3389/fncel.2020.00229 Text en Copyright © 2020 Fenrich, Mrdenovic, Balog, Tomic, Zjalic, Roncevic, Mandic, Debeljak and Heffer. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Neuroscience
Fenrich, Matija
Mrdenovic, Stefan
Balog, Marta
Tomic, Svetlana
Zjalic, Milorad
Roncevic, Alen
Mandic, Dario
Debeljak, Zeljko
Heffer, Marija
SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title_full SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title_fullStr SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title_full_unstemmed SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title_short SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
title_sort sars-cov-2 dissemination through peripheral nerves explains multiple organ injury
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419602/
https://www.ncbi.nlm.nih.gov/pubmed/32848621
http://dx.doi.org/10.3389/fncel.2020.00229
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