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Researchers discover how SARS-CoV-2 reaches the brains of COVID-19 patients



SARS-CoV-2 ciliated cells in olfactory mucosa

The electron microscope image (ultra-thin section, artificially colored) shows part of the ciliated cells in the olfactory mucosa. A large number of intact SARS-CoV-2 particles (red) were found both inside and in the cell process. Yellow: motor protein. Image credit: Michael Laue / RKI and Carsten Dittmayer / Charité

Sample from autopsy tissue, from CharityUniversity of Berlin Medicine The mechanism by which the new coronavirus can reach the brains of patients with the following diseases has been studied Coronavirus disease, And the immune system’s response to the virus.the result shows SARS-CoV-2 Enter the brain through nerve cells in the olfactory mucosa, has been published in Natural Neuroscience. For the first time, researchers were able to generate electron microscope images of complete coronavirus particles inside the olfactory mucosa.

Now realize Coronavirus disease It is not a pure respiratory disease.In addition to affecting the lungs SARS-CoV-2 Affects the cardiovascular system, gastrointestinal tract and central nervous system.More than a third of people suffer from Coronavirus disease Report neurological symptoms such as loss or change of smell or taste, headache, fatigue, dizziness, and nausea. In some patients, the disease may even lead to stroke or other serious diseases. So far, researchers have suspected that these manifestations must be caused by the virus entering and infecting specific cells in the brain.But how SARS-CoV-2 reach there? Under the joint leadership of Dr. Helena Radbruch, CharityThe University’s Department of Neuropathology and the head of the department, Professor Frank Heppner, is a multidisciplinary research team that has tracked how the virus enters the central nervous system and then invades the brain.

Nerve cells in olfactory mucosa infected with SARS-CoV-2

Immunofluorescence staining showed that nerve cells (pink) inside the olfactory mucosa had been infected by SARS-CoV-2 (yellow). Supporting (epithelial) cells are shown in blue.Image credit: Jonas Franz/University of Göttingen

As part of this research, experts from the fields of neuropathology, pathology, forensic medicine, virology and clinical care studied tissue samples from 33 patients (average age 72 years) Charity Or go to the University of Göttingen Medical Center after signing the contract Coronavirus disease. The researchers used the latest technology to analyze samples of the olfactory mucosa and four different brain regions of the deceased.Tissue samples and different cells were tested SARS-CoV-2 Genetic material and the “spike protein” found on the surface of the virus. The research team provided evidence of the virus in the different neuroanatomical structures that connect the eyes, mouth, and nose to the brainstem. The olfactory mucosa showed the highest viral load. Using a special tissue stain, the researchers were able to produce the first electron microscope image of a complete coronavirus particle in the olfactory mucosa. These are found in nerve cells and in the process of extending from nearby supporting (epithelial) cells. All samples used in this type of image-based analysis must be of the highest quality. To ensure this, researchers ensure that all clinical and pathological processes are closely integrated and supported by a complete infrastructure.

“These data support the following views: SARS-CoV-2 The olfactory mucosa can be used as an entrance to the brain. “The close anatomical proximity of mucosal cells, blood vessels and nerve cells in this area also supports this. “Once inside the olfactory mucosa, the virus seems to use neuroanatomical connections such as the olfactory nerve to reach the brain,” the neuropathologist Added. “But it must be emphasized that Coronavirus disease The patients participating in the study had a disease defined as a serious disease, and belonged to the group of patients whose disease proved fatal. Therefore, it is not necessary to transfer our research results to cases of mild or moderate disease. “

The way the virus spreads from nerve cells remains to be fully elucidated. Dr. Radbruch explained: “Our data show that the virus transfers from nerve cells to nerve cells and then reaches the brain.” She added: “However, this virus is also likely to be transported through blood vessels because it is also found on the blood vessel walls of the brain. Evidence of this virus.” SARS-CoV-2 It’s not the only virus that can reach the brain in certain ways. “Other examples include herpes simplex virus and rabies virus,” Dr. Radbruch explained.

Researchers also studied how the immune system responds to infections. SARS-CoV-2. In addition to finding evidence of activated immune cells in the brain and olfactory mucosa, they also tested the immune characteristics of these cells in brain fluid. In some research cases, researchers have also discovered tissue damage caused by stroke due to thromboembolism (ie, blood clots blocking blood vessels). “In our eyes, SARS-CoV-2 The protein in the nerve cells of the olfactory mucosa provides a good explanation Coronavirus disease Patients such as loss of smell or taste. “Professor Heppner explained. “We also found SARS-CoV-2 In areas of the brain that control important functions such as breathing.Can not be ruled out in critically ill patients Coronavirus disease, The presence of the virus in these areas of the brain will have an intensified impact on respiratory function, thereby increasing the cause SARS-CoV-2 lung infection. Similar problems may occur in cardiovascular function. “

Reference: Jenny Meinhardt, Josefine Radke, Carsten Dittmayer, Jonas Franz, Carolina Thomas, Ronja Mothes, Michael Laue, Julia Schneider “The SARS-CoV-2 Invasion of the Olfactory Mucosa is the Port of Entry into the Central Nervous System of COVID-19 Individuals”, Sebastian Brünink, Selina Greuel, Malte Lehmann, Olga Hassan, Tom A Tom Aschman, Elisa Schumann, Robert Lorenz Tsai (Christian Conrad), Roland Eils (Roland Eils), Werner Stenzel (Werner Stenzel) ), Marc Windgassen, Larissa Rößler, Hans-Hilmar Goebel, Hans R. Geldblum, Hubert Martin, Andreas Nitsche, Walter J. Schultz Schafer (Salm Hakroush), Martin Winkler (Marty S., Barbara Ingol) De Hepner, Christina Stadman, Christian Drouston, Victor Michael Koeman, Helena Radbruch and Frank Hepner, November 30, 2020 , Natural Neuroscience.
DOI: 10.1038 / s41593-020-00758-5




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