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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00229/full |
| _version_ | 1818152487779041280 |
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| author | Matija Fenrich Stefan Mrdenovic Stefan Mrdenovic Marta Balog Svetlana Tomic Svetlana Tomic Milorad Zjalic Alen Roncevic Dario Mandic Dario Mandic Zeljko Debeljak Zeljko Debeljak Marija Heffer |
| author_facet | Matija Fenrich Stefan Mrdenovic Stefan Mrdenovic Marta Balog Svetlana Tomic Svetlana Tomic Milorad Zjalic Alen Roncevic Dario Mandic Dario Mandic Zeljko Debeljak Zeljko Debeljak Marija Heffer |
| author_sort | Matija Fenrich |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T13:55:30Z |
| format | Article |
| id | doaj.art-627d6613b5b9478d8a61f3431a76368f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-11T13:55:30Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-627d6613b5b9478d8a61f3431a76368f2022-12-22T01:04:05ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-08-011410.3389/fncel.2020.00229553241SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ InjuryMatija Fenrich0Stefan Mrdenovic1Stefan Mrdenovic2Marta Balog3Svetlana Tomic4Svetlana Tomic5Milorad Zjalic6Alen Roncevic7Dario Mandic8Dario Mandic9Zeljko Debeljak10Zeljko Debeljak11Marija Heffer12Laboratory of Neurobiology, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Hematology, Clinic of Internal Medicine, University Hospital Osijek, Osijek, CroatiaDepartment of Internal Medicine, Family Medicine and History of Medicine, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaLaboratory of Neurobiology, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaClinic of Neurology, University Hospital Osijek, Osijek, CroatiaDepartment of Neurology and Neurosurgery, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaLaboratory of Neurobiology, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaLaboratory of Neurobiology, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaClinical Institute of Laboratory Diagnostics, University Hospital Osijek, Osijek, CroatiaClinical Institute of Laboratory Diagnostics, University Hospital Osijek, Osijek, CroatiaDepartment of Pharmacology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaLaboratory of Neurobiology, Department of Medical Biology and Genetics, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaCoronavirus 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.https://www.frontiersin.org/article/10.3389/fncel.2020.00229/fullSARS-CoV-2neurotropic infectionaxonal transportperipheral nervesneurological symptomsmultiple organ failure |
| spellingShingle | Matija Fenrich Stefan Mrdenovic Stefan Mrdenovic Marta Balog Svetlana Tomic Svetlana Tomic Milorad Zjalic Alen Roncevic Dario Mandic Dario Mandic Zeljko Debeljak Zeljko Debeljak Marija Heffer SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury Frontiers in Cellular Neuroscience SARS-CoV-2 neurotropic infection axonal transport peripheral nerves neurological symptoms multiple organ failure |
| 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 | SARS-CoV-2 neurotropic infection axonal transport peripheral nerves neurological symptoms multiple organ failure |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00229/full |
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