- 5 hypothesized mechanisms 
- detailed summaries in child nodes
- 1 for taste and chemesthesis (included after node: SARS-CoV-2 Targets Taste and Chemesthesis)


Hypothesized mechanisms at molecular level that link infection of COVID-19 to the acute changes in smell


- 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) 


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


Underlying Mechanism of SARS-CoV-2 targeting chemical senses--Olfaction

- 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) 


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