SARS-CoV-2 might enter the brain through your nose

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SARS-CoV-2 might enter the brain of people through the nose, according to an autopsy study which may help explain the neurological symptoms such as loss of smell, taste, headache, fatigue and nausea. Previous research had described the presence of viral RNA – genetic material – in the brain and cerebrospinal fluid, but researchers couldn’t explain how the virus got there to begin with. International researchers performed autopsies on 33 patients who died with COVID-19 and found virus RNA and protein in the brain and nasopharynx (the upper throat behind the nose). The authors say the spike protein in certain types of cells might exploit the fact that these locations are close to the brain and sneak through, infecting neurons for smell and taste as well as areas of the brain that receive this information.

Journal/conference: Nature Neuroscience

Link to research (DOI): 10.1038/s41593-020-00758-5

Organisation/s: Charité–Universitätsmedizin Berlin, Germany

Funder: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy EXC-2049-390688087, as well as SFB TRR 167 and HE 3130/6-1 to F.L.H., SFB 958/Z02 to J.S., SFB TRR 130 TP17 to H.R., EXC 2067/1-390729940, SFB TRR 274 and STA 1389/5-1 to C.S. and SFB TRR 241 to B.S. and A.A.K., by the German Center for Neurodegenerative Diseases (DZNE) Berlin, by the European Union (PHAGO, 115976; Innovative Medicines Initiative-2; FP7-PEOPLE-2012-ITN: NeuroKine) and by the Ministry for Science and Education of Lower Saxony through the program ‘Niedersächsisches Vorab’ to J.F. Furthermore, we thank the Charité Foundation (Max Rubner Preis 2016) for financial support to C. Dittmayer.

Media release

1.  Neuroscience: SARS-CoV-2 may enter the brain via the nose

SARS-CoV-2 may enter the brain of people through the nose, suggests an autopsy study published in Nature Neuroscience. These findings may help explain some of the neurological symptoms observed in COVID-19 patients and may inform diagnosis and measures to prevent infection.

SARS-CoV-2 not only affects the respiratory tract but also impacts the central nervous system (CNS), resulting in neurological symptoms such as loss of smell, taste, headache, fatigue and nausea. Although recent research has described the presence of viral RNA in the brain and cerebrospinal fluid, it remains unclear where the virus enters and how it is distributed within the brain.

Frank Heppner and colleagues examined the nasopharnyx (the upper part of the throat that connects to the nasal cavity), a likely first site of viral infection and replication, and the brains of 33 patients (22 males and 11 females) who died with COVID-19. The median age at the time of death was 71.6 years, and the time from onset of COVID-19 symptoms to death was a median of 31 days. The authors found the presence of SARS-CoV-2 RNA and protein in the brain and nasopharynx. Intact virus particles were also detected in the nasopharynx. The highest levels of viral RNA were found in the olfactory mucous membrane. They noted that disease duration was inversely correlated with the amount of detectable virus, indicating that higher SARS-CoV-2 RNA levels were found in cases with shorter disease duration.

The authors also found SARS-CoV-2 spike protein in certain types of cells within the olfactory mucous layer, where it may exploit the proximity of endothelial and nervous tissue to gain entry to the brain. In some patients, SARS-CoV-2 spike protein was found in cells expressing markers of neurons, suggesting that olfactory sensory neurons may be infected, as well as in the brain areas that receive smell and taste signals.  SARS-CoV-2 was also found in other areas of the nervous system, including the medulla oblongata — the primary respiratory and cardiovascular control center of the brain.

Further COVID-19 autopsy studies that include a broad range of sampling are needed to identify the precise mechanisms that mediate the virus’s entry into the brain, and examine other potential ports of entry.

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