Figure 3.

Timetable of the events that ensue when the sustentacular support cell (SUS) is damaged or eliminated.

This figure summarizes the events when the SUS is damaged by either a toxin or due to virus infection. Notably, damage of the SUS causes within 2–3 h a physical separation of the SUS from the olfactory receptor neuron (ORN), swelling of the knob and its degeneration, and retraction of the cilia [27,51,63., 64., 65.]. Deciliation continues from 2 to 48 h. The ORN resumes an immature stage of its dendritic extension, with focus on growth of its processes rather than on neurotransmission and sensory transduction. Gene expression of odorant receptors (ORs) is downregulated at 2 days (mouse [52]), 3 days (zebrafish [63]), and 4 days (hamster [22]) after inoculation. Odorant-binding proteins (OBPs) and receptor transporting protein 1 (RTP1) are also reduced [52]. In most animal models, loss of smell is evident as early as 2 days after lesion of SUS (mouse) and, depending on the animal model, anosmia lasts from 2 to 8 days. In humans, it lasts from 7 to 10 days (mean values) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [37]. The stem cells in the basal layers begin to divide at 3 days after SUS damage [66], and the first newly regenerated SUS appear at 4–8 days [22,64]. Recovery of smell begins at 4 days after SUS lesion in the mouse, at 8 days in the hamster [75], and the olfactory epithelium appears fully intact in the hamster at 7 days [74] or 14 days [51]. Human data on recovery of smell are according to pertinent studies [36,37,120,121].