- taste and chemesthesis may be disturbed independently of smell in COVID-19 patients 
- individual TRCs are constantly being renewed by stem cells, and thus taste function and perception also depend on rapid and reliable production of the proper proportions of each of the different TRCs 
- taste dysfunction in COVID-19 patients may be caused or exacerbated by insufficient TRC renewal due to SARS-CoV-2 stem cell damage.
- ACE2 is expressed by sour-sensing type III TRCs, thus could be invade by SARS-CoV-2
- the loss of support cells could lead to taste bud collapse via cell death and/ or reduced efficacy of taste signals to gustatory nerves 
- local inflammatory processes could therefore alter stem cell properties and ultimately influence taste perception 


What mechanistic hypotheses can explain the specific impact of SARS-CoV-2 on taste function?

(F) Taste and chemesthetic disturbances may result from:
- the direct infection of cells in the tongue(e.g. taste receptor cells) 
- the indirect consequences of inflammation
- damage following the release of inflammatory cytokines 
- the loss of support cells could lead to taste bud cell death and/ or reduced efficacy of taste signals to gustatory nerves

The loss of taste may result from the direct infection of cells in the tongue or the consequences of  inflammatory cytokines

- RNA profiling of tongue epithelium 
- datasets of mice and human
-  type I TRCs and precursor TRCs have yet to be profiled, and ACE2 is not detected in sensory neuron afferents

ACE2 expression in taste relevant cell populations

- The taste repertoire is restricted to non-volatile sour, salt, sweet, bitter, and umami stimuli that directly activate taste buds on the tongue. 
- Taste perception is supported by taste buds, which have a characteristic distribution on the tongue and which house taste receptor cells (TRCs) (Figure 4): type I for support, type II for sweet, bitter, or umami, and type III for sour) 


Smith College

- 60-90 percent of patients experience loss of chemical senses without significant rhinorrhea or nasal congestion 
- SARS-CoV-2 might alter the cells and circuits involved in chemosensory processing 
- the loss of smell and taste is more predictive than all other symptoms
- scratch-and sniff cards may be used to screen CoV-19 in community (more research needed)

COVID-19 targets the chemical senses


Cooper, K. W., Brann, D. H., Farruggia, M. C., Bhutani, S., Pellegrino, R., Tsukahara, T., ... & Albers, M. W. (2020). COVID-19 and the chemical senses: supporting players take center stage. Neuron.
https://doi.org/10.1016/j.neuron.2020.06.032
https://www.sciencedirect.com/science/article/pii/S0896627320304864

COVID-19 and the Chemical Senses: Supporting Players Take Center Stage

- viral infections lead to long-lasting (i.e., months) post-viral anosmia, which is thought to result from direct damage to the olfactory sensory neurons responsible for odor detection in the olfactory epithelium 
- natural history of COVID-19-associated anosmia argues that SARS-CoV-2 attacks the olfactory system through mechanisms distinct from those used by the more benign endemic coronaviruses —recover faster

Differences to viral infection anosmia and common-cold anosmia


- SARS-CoV-2 infects cells through interactions between its S protein and the ACE2 receptor on target cells
- recent work in macaques, ferrets, and cats identifies the nasal epithelium as a major source of viral RNA after SARS-CoV-2 infection 

Human Olfactory Epithelium 
- Olfactory Sensory Neurons do not express ACE2 
- ACE2 expressed in key support cells (including sustentacular, Bowman’s gland, and microvillar cells) 


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