Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019

The omicron variant of severe acute respiratory syndrome coronavirus 2 causes 3-4-fold less anosmia prevalence than previous variants. The molecular mechanisms responsible for reduced infection of olfactory cells may explain the sparing of olfactory function with the omicron variant. The omicron variant of severe acute respiratory syndrome coronavirus 2 causes much less olfactory dysfunction than the previous variants. There are several potential mechanisms for how omicron may change tissue tropism and spare olfactory function. The new mutations make omicron more hydrophobic and alkaline than previous variants, which may reduce penetration of the mucus layer. Overall, the new mutations minimally change receptor binding affinity, but entry efficiency into host cells is reduced in cells expressing transmembrane serine protease 2 (TMPRSS2). Because the support cells in the olfactory epithelium abundantly express TMPRSS2, these main target cells in the olfactory epithelium may become infected less by the new omicron variant.