November 30, 2020

expert reaction to study suggesting SARS-CoV-2 may enter central nervous system via the nose

A study published in Nature Neuroscience suggests that SARS-CoV-2 may enter the nervous system by crossing the nasal epithelium.

Prof Roger Morris, Professor of Molecular Neurobiology, Acting Head of Department of Chemistry, King’s College London (KCL), said:

“This is a serious paper, providing strong, credible, evidence that a major (although not sole) route of entry enabling SARS-CoV2 to infect and dangerously damage patients is to invade the brain via the well understood olfactory route.  Olfactory neurons (the ones we smell with) line cavities in our nose,  where  they sample not just odours, but also inhaled viruses.  These neurons have on their surface a receptor (ACE2) that binds the Covid virus, directing them to infect the neurons.  Long  cellular processes (axons) connect to the neurons in the front of the brain, from where infection spreads to, and damages, other neurons and blood vessels, inducing an inflammatory response.

“This investigation is the result of an extensive German clinical and scientific network, together bringing a  strong interdisciplinary approach that adds to the reliability of this research.  The numbers of patients studied (33 in all) is small, but the virus is identified at both protein and mRNA level along a well defined route of pathogen entry to the brain via the olfactory mucosa, factors that add considerable weight to their findings.

Infection via this route would explain the lack of smell and taste that is a wide spread early symptom of Covid infection; and will be relevant to understanding at least some of the causes of ‘long Covid’.”

Prof Gitte Moos Knudsen, Chair if the Department of Neurology and Neurobiology Research Unit, Copenhagen University Hospital, said:

“The findings are not surprising. Central nervous system (CNS) entry through the nasal epithelium is a recognized mode of viral uptake and would not be unique to SARS-CoV-2.

“It would be interesting to know to what extent the virus gets CNS access through the nasal route and to what extent it crosses into the brain through (micro)vascular changes such as stroke which were observed in 8/33 patients, and possibly went undetected in additional patients.

“Overall this does not fundamentally change our current understanding of the mechanisms of action of this virus on the brain.”

‘Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19’ by Jenny Meinhardt et al. was published in Nature Neuroscience on Monday 30 November.

DOI: https://doi.org/10.1038/s41593-020-00758-5

Declared interests

None received.