So Why Do We Lose Our Smell With Covid-19

    A very common (and scary) symptom of the Covid-19 virus is loss of smell or taste. Reports of these symptoms were surprising, as many of our familiar viruses do not have this effect. We can examine the mechanism for this by looking into the virus's ability to cross the blood brain barrier. One article published shared one way the virus could possibly infiltrate our brain, the S1 protein. The results of the study showed that the S1 protein or viral binding protein was able to cross the blood brain barrier. Not only did the S1 protein transverse the blood brain barrier, but it was taken up by at least 11 brain regions. The S1 protein is a cleaved binding protein from the SARS-cov-2 virus, this protein is thought to behave very similarly to the actual virus, which could explain the responses in the brain.

Another article explored the possibility of both direct and indirect infection for the virus. A direct infection of Covid-19 has been characterized as a detection of the SARS-co-2 RNA in the cerebral spinal fluid. The authors have predicted two pathways that the rna could travel into the brain, one being axonal transport. Specifically through certain cranial nerves, like the olfactory nerve. The hypothesis for anosmia (loss of smell) is the virus entering the olfactory bulb.

To dive deeper into the exact process of invasion, we can explore another article. The mechanism for loss of smell can be explained by expression of a protein in the olfactory epithelium, ACE2 and a gene TMPRSS2. They are found in the sustentacular cells of the epithelium. The presence of these in the olfactory epithelium can increase virus binding capacity. The results of this study found that ACE2 and TMPRSS2 are found more abundantly in non-neuronal cells, meaning that those non-neuronal cells are the primary entry into the olfactory epithelium. Another interesting find from this article is the idea of age and loss of smell/viral contraction. Older age increases the amount of ACE2 and the gene expression of TMPRSS2, these being the primary receptors for SARS-cov-2. This might explain the increased contraction risk as individuals age and the increased loss of smell.

Loss of smell could be associated with nasal blockage or congestion, but many reports of the anosmia have not been directly linked to blockage, rather the virus's entry into the central nervous system, eventually making its way into the olfactory neuroepithelium and the olfactory bulb. The virus has the ability to invade these pathways by S1 proteins or rna in the cerebral spinal fluid.

Rhea, E.M., Logsdon, A.F., Hansen, K.M. et al. The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice. Nat Neurosci 24, 368–378 (2021). https://doi-org.dml.regis.edu/10.1038/s41593-020-00771-8

Bougakov, D., Podell, K. & Goldberg, E. Multiple Neuroinvasive Pathways in COVID-19.Mol Neurobiol 58, 564–575 (2021). https://doi-org.dml.regis.edu/10.1007/s12035-020-02152-5Bilinska, K., Jakubowska, P., Von Bartheld, C. S., & Butowt, R. (2020). Expression of the SARS-COV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: Identification of cell types and trends with age. ACS Chemical Neuroscience, 11(11), 1555–1562. https://doi.org/10.1021/acschemneuro.0c00210