SARS-CoV-2 may penetrate the CNS by crossing the neural–mucosal interface in olfactory mucosa, post-mortem findings from Europe suggest.
Neuropathologists have found evidence in autopsy samples from 33 people who died of COVID-19 disease that the SARS-CoV-2 virus exhibits neurotropism and may enter the nervous system by exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings.
The findings, published in Nature Neuroscience may also help explain some of the neurological symptoms observed in COVID-19 patients and may inform diagnosis and measures to prevent infection, according to researchers from Charité–Universitätsmedizin Berlin.
Dr Frank Heppner and colleagues examined the nasopharnyx and the brains of 22 males and 11 females who died with COVID-19 (median age 71.6 years).
They found evidence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain such as the olfactory bulb, and intact CoV particles in the nasopharynx.
The highest levels of viral RNA were found in the olfactory mucous membrane. SARS-CoV-2 was also found in other areas of the CNS, including the medulla oblongata.
The amount of detectable virus was inversely correlated with disease duration, indicating that higher SARS-CoV-2 RNA levels were found in cases with shorter disease duration.
The researchers also noted morphological changes associated with infection such as thromboembolic ischaemic infarction of the CNS, with a local CNS response mediated through HLA-DR+ microglia as effectors of a myeloid-driven inflammatory response.
However, although it was suspected that SARS-CoV-2 neuroinvasion occurred via axonal transport, morphological detection of single viral particles in axons would be very difficult owing to the very low number of viral particles that are expected, given that the viral reproduction apparatus is thought to be located in the neuronal somata.
“Taking our findings together, we provide evidence that SARS-CoV-2 neuroinvasion can occur at the neural–mucosal interface by transmucosal entry via regional nervous structures,” they wrote.
“This may be followed by transport along the olfactory tract of the CNS, thus explaining some of the well-documented neurological symptoms in COVID-19, including alterations of smell and taste perception.”
“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,” they concluded.