The goal was to determine whether SARS-CoV-2 can enter the brain via enteric neurons and pass through the gut brain axis, into the brain.

Methods:

• They immunostained ACE2 and TMPRSS2, two proteinases that cause SARS-CoV-2 to enter cells, in the area between the nervous system and non-nervous system organs, in the small and large intestine, choroid plexus, and the brain parenchyma.
• They collected tissue samples from patients who had been operated on and cadavers.

Results:

• The ACE2 and TMPRSS2 were found in layers in the intestinal wall and ENS.
• TMPRSS2 was found in the cytoplasm of enteric epithelial cells.
• ACE2 was found in the enteric neurons and glial cells, but not in the dendrites or axons of enteric neurons
• ACE2 and TMPRSS2 were both strongly found in the choroid plexus, but were weakly found in the brain parenchyma
• The results support the hypothesis that SARS-CoV-2 can enter the brain via enteric neurons, as these cells do express ACE2 and TMPRSS2
• Further, ACE2 and TMPRSS2 were found in the glial cells of the ENS, which infection of these cells might harm the immune response, which may contribute to the cytokine storm.
• Further, ACE2 and TMPRSS2 were found in the glial cells of the ENS, which infection of these cells might harm the immune response, which may contribute to the cytokine storm.
• That ACE2 and TMPRSS2 were found in the choroid plexus suggests a possible route through the choroid plexus, through the CFS, and one through the fenestrated blood vessels.
• The weak stainings of the brain parenchyma reject the hypothesis that the virus enters the brain through the blood brain barrier.
• The entry through the olfactory neurons is also unlikely because the olfactory receptor neurons did not express ACE2, only the sustentacular cells.