- 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) 


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) 


SARS-CoV-2 Targets Taste and Chemesthesis

- 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)

Smith College

- the loss of smell or taste is one of the first occurred COVID-19 symptoms

- SARS-CoV-2 like SARS-CoV and MERS-CoV could infect the nervous system through neurons in the nasal passage targeting olfactory bulb

- Experiment on transgenic mice expressing human ACE2 showed SARS-CoV enter CNS through neurons in the nose. 

- SARS-CoV-2 could work its way up to the olfactory mucosa, which consists of epithelium cells, blood vessels, and the axons from olfactory neurons, which lead to the frontal lobe.

- Loss of sense could be caused by inflammation as the body fights the virus

- SARS-CoV-2 infects medulla oblongata— part of the brain stem that serves as the control center for the heart and the lungs—causing acute respiratory failure for patients e.g. loss of involuntary breathing 

- SARS-CoV-2 cross BBB by circulating through the blood and then attack ACE2 receptors in the endothelia that lines blood capillaries in the brain, causing swelling and compression of brain stem


Lost smell and taste hint COVID-19 can target the nervous system

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

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