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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