Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal im-aging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light -micro-scopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral inva-sion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrap-ping olfactory axon fascicles in the lamina propria of the olfactory mucosa.

Automated summary

The study investigated the possibility of SARS-CoV-2 invading the brain through the olfactory projection. The researchers obtained tissue and fluid samples from deceased COVID-19 patients and found no evidence of viral invasion in the olfactory bulb and frontal lobe. Instead, they identified anatomical barriers between the olfactory epithelium and the olfactory nerve.