How the Coronavirus Gets Into the Brain

The nose-brain connection may hold the answer, researchers find

Photo by Natasha Connell on Unsplash

It’s well known that Covid-19 is primarily a respiratory disease, but it has significant effects on other realms of the body, too. Its impact on the brain has garnered a lot of attention: The nausea, vomiting, headache, fatigue, and loss of smell and taste experienced by a third of people with Covid-19 could all be considered neurological symptoms.

What scientists haven’t quite figured out is how the virus gets into the brain in the first place.

The brain — which is part of the central nervous system, together with the spinal cord — is relatively well protected from invaders. The blood-brain barrier, for example, is a semipermeable membrane that allows beneficial nutrients circulating in the blood to reach the brain but keeps pathogens out. When a virus manages to reach the brain, it’s worth noting and asking how.

Research published Monday in the journal Nature Neuroscience sheds light on how SARS-CoV-2 may do so. A team led by Helena Radbruch, PhD, and Frank L. Heppner, PhD, of the Charité–Universitätsmedizin Berlin examined the bodies of 33 people who had died of Covid-19 and concluded that the virus likely entered the brain through the nose.

They detected viral RNA in the brain and the nasopharynx, the upper region of the throat that connects to the nasal cavity (and is also where viral infection and replication is first thought to take place). Bordered on the bottom by the roof of the mouth and on the top by the space that holds the brain, the nasal cavity is the mound-shaped enclosure that makes the inside of the nose.

They found the most viral RNA in the olfactory mucosa, the lining at the top of the nasal cavity. In part because of its close proximity to the brain, the researchers think the olfactory mucosa is the most likely “port of entry” into the central nervous system. Some brain cells project into the olfactory mucosa, and these may act like highways for the virus to travel further into the brain, once it has crossed over from the nose.

In their hunt for the presence of the coronavirus in the nose and brain, the researchers also detected it in the cerebellum — a part of the brain that is not directly connected to the olfactory mucosa. This suggests that there are other, nonnasal roads leading to the brain. (One possibility is that it rides across the blood-brain barrier in white blood cells; another is that it gets in through the central nervous system’s endothelium.) They also detected low levels of the coronavirus in parts of the eyes and oral mucosa, suggesting that the virus may also be able to enter the central nervous system through these routes.

This is early research, partially limited by a small sample size, and partially by the tricky nature of doing autopsy research during a global pandemic. Infected cells may die in the variable time between a person’s death and the moment a scientist can examine their body, which no doubt complicate any effort to trace the path the virus travels. “One caveat to note with the Covid-19 cases reported here,” the authors write, “is the relatively long postmortem interval, an almost insurmountable obstacle in autopsy studies, especially when performed under the emergency-like conditions encountered during a pandemic situation.”



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Yasmin Tayag

Yasmin Tayag


Editor, Medium Coronavirus Blog. Senior editor at Future Human by OneZero. Previously: science at Inverse, genetics at NYU.