How Covid-19 Enters The Brain

Articles COVID-19

To our knowledge, there are seven types of coronaviruses that naturally infect humans; the current, most prominent one being of course, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019–dubbed Covid-19.

The respiratory manifestations of Covid-19 have been well investigated; although, with little research to suggest its impact on the neurology of the individual. Emerging evidence seems to solidify this revelation, though. That said, this association is not distinct to Covid-19, and perhaps incited the investigation into this nexus in the first place. The neuroinvasive potential of Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV-1), evolutionarily closely related to SARS-CoV-2, are known to cause disease in the central and peripheral nervous systems.

Our knowledge of the virus commonly dictates that SARS-CoV-2, along with affecting the lungs, impacts the cardiovascular system, the gastrointestinal tract, and the central nervous system. Over a third of affected individuals report neurological symptoms like loss of, or change in, sense of smell or taste, headaches, fatigue, dizziness, and nausea. In some patients, the disease can even result in stroke or other serious conditions. Until recently, researchers had suspected that these manifestations must be caused by the virus entering and infecting specific cells in the brain.

However, an understanding of how SARS-CoV-2 enters the brain itself was largely wanting. To analyse this particular link, a team of researchers, using post-mortem tissue samples began to study the mechanisms by which the virus can reach the brains of patients with Covid-19.

Image 1: An overall comparison of the 3 main Coronaviruses

The researchers studied autopsy material from 33 individuals with COVID-19. The focus group consisted of 22 males, 11 females with an average age of 72 years. Using various techniques and technologies, they analysed tissue samples taken from the deceased patients’ olfactory mucosa (located in the upper region of the nasal cavity) and from four different brain regions. Both the tissue samples and distinct cells were tested for SARS-CoV-2 genetic material.

The researchers provided evidence of the virus in different neuroanatomical structures which connect the eyes, mouth, and nose with the brain stem. The olfactory mucosa revealed the highest viral load. Using a specific tissue staining technique (called immunohistochemical stains), the researchers were able to produce the first-ever electron microscopy images of intact coronavirus particles within the olfactory mucosa. These were found both inside nerve cells and in the processes extending from nearby supporting (epithelial) cells

Image 2: Showing (a) location of sampled tissues, and (b) detection of SARS-CoV-2 in sampled tissues of deceased individuals with COVID-19. The olfactory mucosa (shown by R1 on image (a) and (b) shows the highest viral load). 

This is additionally supported by the close anatomical proximity of mucosal cells, blood vessels and nerve cells in the area. When the virus has entered the olfactory mucosa, it seems to use neuroanatomical connections, such as the olfactory nerve, to reach the brain. However, it is essential to highlight that those involved in the study had what would be classified as severe disease, belonging to that small group of patients in whom the disease proves fatal. Therefore, it is not necessarily possible to transfer the results of the study to cases with mild or moderate disease.

Knowledge of SARS-CoV-2 neurotropism (attraction of certain pathogens to neural tissue) and potential mechanisms of CNS entry and viral distribution is key for a better understanding of COVID-19 diagnosis, prognosis and interventional measures.

Original Source: 
Meinhardt J, Radke J, Dittmayer C. et al. (2020)”Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.” Nature Neuroscience.

Image 1 Source 

Image 2 Source:
Nature neuroscience. “Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19” 

Featured Image Source:
TBU News. “How Fear is Used.”

Edited by Malavika Ramanand 

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