The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia

BACKGROUND: Recent evidence demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagates in intestinal epithelial cells expressing Angiotensin-Converting Enzyme 2 (ACE2), implying that these cells represent an important entry site for the viral infection Nicotinic receptors (nAChRs) have been put forward as potential regulators of inflammation and of ACE2 expression As vagus nerve stimulation (VNS) activates nAChRs, we aimed to investigate whether VNS can be instrumental in affecting intestinal epithelial ACE2 expression METHODS: By using publicly available datasets we qualified epithelial ACE2 expression in human intestine, and assessed gene co-expression of ACE2 and SARS-CoV-2 priming Transmembrane Serine Protease 2 (TMPRSS2) with nAChRs in intestinal epithelial cells Next, we investigated mouse and human ACE2 expression in intestinal tissues after chronic VNS via implanted devices RESULTS: We show co-expression of ACE2 and TMPRSS2 with nAChRs and α7 nAChR in particular in intestinal stem cells, goblet cells, and enterocytes However, VNS did not affect ACE2 expression in murine or human intestinal tissue, albeit in colitis setting CONCLUSIONS: ACE2 and TMPRSS2 are specifically expressed in epithelial cells of human intestine, and both are co-expressed with nAChRs However, no evidence for regulation of ACE2 expression through VNS could be found Hence, a therapeutic value of VNS with respect to SARS-CoV-2 infection risk through ACE2 receptor modulation in intestinal epithelia could not be established