Coronavirus: Possible Routes by Which SARS-Cov-2 Could Be Entering the Brain

How does the coronavirus enter the brain?

Traces of the SARS-CoV-2 coronavirus have been found several times in the brains of people who have died of Covid-19 in autopsies. Neurological disorders, taking into account the anosmia, are regularly reported by the patients. This revives the hypothesis that the coronavirus is able to penetrate the central nervous system. One of the most important points that the researchers do not yet understand is the path that the coronavirus takes to the brain. The brain is isolated from the blood flow through the blood-brain barrier. Pathogens or toxins that migrate through the bloodstream are filtered out through this cell membrane, only nutrients and waste products can pass through it.

Woman Smelling Flower

Woman Smelling Flower

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How does SARS-Cov-2 avoid the blood-brain barrier? The researchers’ first instinct was to look at the neurons. SARS-Cov-2 could enter the olfactory system through the axon tips of the neurons and migrate to the cell bodies in the olfactory bulb.

A study published in Nature Neuroscience on November 30, 2020, suggests a different route, which does not exclude the above-mentioned one. At the Berlin Institute of Health, researchers performed 33 autopsies of Covid-19 deaths and searched for the RNA of the virus in different regions of the nasopharynx and brain (olfactory mucosa, olfactory bulb, uvula, trigeminal ganglion, medulla oblongata, and cerebellum).

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The pathways that the coronavirus takes to the brain

The structure that has the most concentration of  SARS-Cov-2 RNA is the olfactory mucosa, which is located in the roof of the nasopharynx. This mucosa forms an interface between the nasopharynx and the olfactory bulb on the other side. The olfactory neurons develop their dendrites in the apical part of this mucosa, which is organized as a pseudostratified epithelium. On the basal side of the mucosa the axons of the nerve cells emerge, they are directly connected to the olfactory bulb in the brain.

These neurons could serve as a highway for the coronavirus to enter the brain, but scientists believe that there is another possibility. SARS-CoV-2 could simply pass through the mucous membrane weakened by the inflammation and then enter the olfactory bulb.

However, autopsies have also revealed SARS-Cov-2 RNA in the cerebellum, an area of the brain remote from the olfactory bulb. To explain this, there is currently only conjecture without any evidence. In their publication, scientists from the Berlin Health Institute mention the possibility that SARS-Cov-2 is carried by lymphocytes that can cross the blood-brain barrier. This study provides valuable information on the ability of the coronavirus to infect the central nervous system via the olfactory mucosa, but it is probably only one route among many others.

Read also: COVID-19: The Nose Is the Easiest Entry Point for the Coronavirus

A recent study suggests that the coronavirus responsible for Covid-19 can infect the central nervous system in the same way as other coronaviruses. Is this related to the cases of anosmia in infected people reported by doctors?

More than 340,000 people who suffer from Covid-19 complain of a triad of symptoms typical of the infection: fever, cough, and shortness of breath. Some also complain of less common symptoms such as headaches, nausea, and vomiting. These symptoms are often associated with a neurological disorder. Do they indicate an invasion of the coronavirus responsible for Covid-19 into the central nervous system?

Yan-Chao Li, a researcher at Jilin University (China), analyzes this hypothesis in an article published in The Journal of Medical Virology on February 27, 2020 (and corrected on March 17, 2020).

Neurotropism of Coronavirus

Although coronaviruses are primarily respiratory viruses, several studies report their ability to infect the central nervous system and cause neurological disorders.

Read also: When Do Symptoms Start to Show Following Coronavirus Infection?

The neurotropism of coronaviruses is well known, especially through the family of beta-coronaviruses, which includes SARS-Cov, MERS-Cov, and SARS-CoV-2, which is currently spreading. The neurons of the central nervous system are often the target cell of the virus causing its degeneration. HEV 67N, a porcine coronavirus, was first identified in the brain of pigs. There is a 91% homology between this strain and a human beta coronavirus, HCoV-OC43, which causes the common cold.

The exact route that the coronaviruses follow is not known, but it appears that the viruses use the synaptic pathways to travel from the cardiorespiratory center to the spinal cord. It is believed that the mechanoreceptors and chemoreceptors of the peripheral nerve endings of the lower respiratory tract are the gateways through which the virus enters the central nervous system.

The neurological symptoms of Covid-19 affect only a minority of people: 8% suffer from headaches and 1% from nausea and vomiting. In contrast, a study of 240 Covid-19 patients described neurological manifestations such as loss of consciousness and acute cerebrovascular disorders in 88% of severe cases studied.

Read also: COVID-19: A Man Suddenly Loses Hearing After Coronavirus Infection

An explanation for anosmia?

In recent days, doctors have reported that a minority of patients complain of anosmia. This is a loss of smell, which is often accompanied by an (acute) loss of taste. Anosmia can be caused by damage to the olfactory nerve, the first cranial nerve that connects the nasal cavity with the olfactory bulb at the base of the brain. If the damage is neurological in nature, the anosmia may be constant.

In the case of Covid-19, does the anosmia indicate an invasion of the virus from the central nervous system?

Not necessarily. Anosmia is a very common symptom in respiratory diseases such as rhinitis or colds. In this case, it is not the olfactory nerve, but a defect in the permeability of the nasal cavities, the congested nose, which prevents odors from reaching the olfactory receptors. The anosmia is then usually temporary.

Read also: Coronavirus Proteins Found in the Eyes of a Patient Cured of COVID-19

The virus has not yet been observed in the brainstem of patients, as was the case with the MERS-CoV and SARS-CoV tests on mice. The neurotropism of SARS-CoV-2, which is responsible for Covid-19, is currently only a suspicion for now and there is a lack of scientific data to prove it with certainty. However, being aware of this possibility could have an impact on management and treatment, which always depends on the symptoms of the disease.

References

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

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