The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction

Abstract

During the first waves of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one of the front-line protections against viral infections, and the immune responses of the nasal mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: the infection of sustentacular cells and the inflammatory reaction of the nasal epithelium. The former triggers OD and the latter likely prolongs OD. These two alternative mechanisms may act in parallel; the infection of sustentacular cells is more important for OD occurrence because sustentacular cells are more likely to be the entry point of SARS-CoV-2 than olfactory neurons and more susceptible to early injury. Furthermore, sustentacular cells abundantly express transmembrane protease, serine 2 (TMPRSS2) and play a major role in the olfactory epithelium. OD occurrence in COVID-19 has revealed crucial roles of sustentacular cells. This review aims to elucidate how immune responses of the nasal epithelium contribute to COVID-19–related OD. Understanding the underlying immune mechanisms of the nasal epithelium in OD may aid in the development of improved medical treatments for COVID-19–related OD.