COVID-19 Related Hyposmia/Anosmia and Ephrin Cells

The article "Ephrin-B/EphB Signaling is Required for Normal Innervation of Lingual Gustatory Papillae" published in 2016 and authored by Treffy et al. assesses how the proteins Ephrin-B and EphB proteins work to signal the growth of lingual gustatory papillae (tastebuds). Through experiments on mice, it was found that the decreased activation/presence of Ephrin-B/EphB correlated with a decreased innervation of lingual gustatory papillae during the stage they were meant to develop during. These proteins are therefore crucial to the development of the ability to taste and creation of the sense’s neural pathways. This raises the question of how a common side affect of COVID-19 infection, the loss of the ability to taste, could be relevant in discussions about lingual gustatory papillae.

While it is common to lose taste and smell during bouts of sickness, many of the people who lost those senses when infected with COVID-19 never regained them (Rabin, 2021). The loss ranges from a decreased sensitivity (hyposmia) to a total loss (anosmia), some of the post-infected even experiencing completely alternative tastes when eating foods they were familiar with prior. Due to this, Zalpoor et al. (2022) and later Al-Saigh et al. (2024) investigated COVID-related anosmia. Zalpoor et al. (2022) explores the possibility of “Ephrin (Eph) receptors as a possible SARS-CoV-2 entry receptor for human host cells in the central nervous system (CNS) and the potential roles of SARS-CoV-2 spike protein in stimulating the Eph receptor downstream signaling pathway for COVID-19-associated neurodegenerative diseases.” Ephrin cells are expressed all throughout the body and organs such as the liver, lungs, and stomach, as well as being the cell linked to taste bud development (Ephrin-B/EphB). If these receptors and proteins were the ones carrying Covid, then was that part of why COVID-19 infected people lost their sense of smell at such high rates? Or could they be targeted as a treatment for anosmia and hyposmia?

Zalpoor et al. highlight the possible proteins that could be targeted as part of a treatment plan. It’s been shown that those with COVID-19 have higher levels of ephrin-A1 proteins than uninfected people, leading to a link between the two. Since this higher amount of an ephrin protein is also related to other neurodegenerative diseases such as Alzeihmer’s and also plays a role in forming new blood cells (angiogenesis) it is important to consider the possibility of COVID-19 affecting Ephrin-B proteins and receptors. By researching more about these receptors, treatments specific to COVID-19 related loss of small can be further developed. 

References

Al-Saigh, N. N., Harb, A. A., & Abdalla, S. (2024). Receptors Involved in COVID-19-Related Anosmia: An Update on the Pathophysiology and the Mechanistic Aspects. International Journal of Molecular Sciences, 25(15), 8527. https://doi.org/10.3390/ijms25158527 

Rabin, R. C. (2021, January 2). Some Covid Survivors Haunted by Loss of Smell and Taste. The New York Times. https://www.nytimes.com/2021/01/02/health/coronavirus-smell-taste.html 

Treffy, R. W., Collins, D., Hoshino, N., Ton, S., Katsevman, G. A., Oleksiak, M., Runge, E. M., Cho, D., Russo, M., Spec, A., Gomulka, J., Henkemeyer, M., & Rochlin, M. W. (2016). Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory Papillae. Developmental Neuroscience, 38(2), 124–138. https://doi.org/10.1159/000444748 

Zalpoor, H., Akbari, A., & Nabi-Afjadi, M. (2022). Ephrin (Eph) receptor and downstream signaling pathways: a promising potential targeted therapy for COVID‑19 and associated cancers and diseases. Human Cell, 35(3), 952–954. https://doi.org/10.1007/s13577-022-00697-2