Around 50% of people confirmed to have COVID-19 report a loss or decrease in their sense of smell. But does this mean that the virus is neuroinvasive through the olfactory neurons? A new study concludes that the olfactory nerve is an unlikely route to brain infection, which is believed to be rare in humans.

Loss of smell = brain infection? Not so fast …

It is now known that one of the most common symptoms of COVID-19 is loss of smell. If the new coronavirus infects the nasal epithelium, does this mean that the virus can get to the brain along the olfactory nerve? Recent publications make it sound like this has been proven: “SARS-CoV-2 olfactory transmucosal invasion as a port for entry into the central nervous system in people with COVID-19” and “The olfactory pathway is a potential pathway for SARS -CoV- 2 to penetrate the central nervous system in rhesus monkeys ”. Such publications and the attention they have received in the media are reason enough to scare COVID-19 patients who have lost their sense of smell. If the virus has impaired their sense of smell, it means the virus is in their brain too – just waiting to cause brain fog to spread throughout the brain and kill the patient, or if they recover, greatly increasing their chance of development increase a neurodegenerative disease?

Olfaction – A Portal To Brain Infection?

Our team of researchers from Poland, France and the United States examined the evidence that the new coronavirus infects olfactory neurons and travels along the axons of the olfactory nerve from the nose to the brain. There is broad consensus that the mandatory viral entry proteins are absent in olfactory receptor neurons. Such entry proteins are abundantly expressed in the carrier cells, which become infected and die, thereby reducing the function of neighboring olfactory receptor neurons. It is widely believed that this is what causes the loss of the sense of smell in COVID-19. The supporting cells regenerate within a few days, the neurons resume their function and the odor returns in most patients within 1-2 weeks. Finding the new coronavirus in axons of the olfactory nerve is extremely rare, making this an ineffective route to brain infection.

The evidence just doesn’t match

Why do many reports advocate an olfactory route to brain infection? One reason for this is that neurons and their supporting cells are closely intertwined and can easily be mixed up in confocal microscopy. Another reason is that the virus can actually reach the brain, especially in genetically engineered mice that have abnormally expressed viral entry proteins. However, careful analysis shows that the time course and route of virus progression in animal models are inconsistent with transmission from olfactory neurons in the nose to second and third order neurons in the brain. Instead, the data shows a rare but fulminant occurrence of the virus in the brain – suggesting a pathway through blood vessels, the cerebrospinal fluid, or through a linkage of nerve fibers that bypass the olfactory bulb and project directly onto targets in the forebrain. We are fortunate that the lack of viral entry proteins in olfactory neurons creates an effective barrier that prevents brain infection via the olfactory pathway.

An illustration of the brain, shown in pink and purple, on a blue background

The new coronavirus can – rarely – be present in the brain, but this seems to have happened in other ways – via blood vessels, cerebrospinal fluid, or nerve fibers other than the olfactory nerve.
(jolygon /

An illustration of the brain, shown in pink and purple, on a blue background

Does the virus replicate in the brain?

It should be emphasized that, unlike some animal models, the virus is rarely found in the human brain. In addition, many studies have relied on methods that do not detect a replicating virus, but instead detect viral RNA or viral proteins that can be systemically rejected and circulated without conclusive evidence of brain infection. The meaning of the viral presence in the brain is still unclear. Some researchers believe that infection of the brainstem and respiratory centers can lead to fatal consequences in COVID-19, while others find that there is no correlation between the detection of viruses in the brain or cerebrospinal fluid and the severity of COVID-19 .

COVID patients who have lost their sense of smell can breathe a sigh of relief. Just because their supporting cells in the nose became infected doesn’t mean the virus found an easy route from the nose to the brain. Our analysis of the current evidence shows that the vast majority of COVID-19 patients will not have a brain infection even if they temporarily lose their sense of smell.

Do you like the blog? Now read the research:

The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from human and animal models


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