The Science Behind the COVID-19’s Loss of Smell and Taste

For those of us who are coffee lovers, nothing compares to the aroma of freshly brewed coffee as we commence our day or the nutty and sweet taste of the morning’s first sip. Nevertheless, for many who have been infected with SARS-CoV-2, the virus that causes COVID-19, simple pleasures like these have been disrupted by the sudden loss of their ability to perceive smell. Approximately, 86% of patients with a mild form of COVID-19 experience olfactory dysfunctions (Lechien et al.). This loss in olfactory functions has been observed to co-occur with the loss of taste and chemesthesis, the process by which chemicals trigger pain, touch, and thermal sensations such as spiciness. A multicenter study of 1,363 patients with COVID-19 utilized objective olfactory evaluations which revealed that 54.7% of patients with mild forms of COVID-19 experienced hyposmia/anosmia, the partial or total loss in the ability to detect odors. Interestingly, despite being one of our most primal senses, olfaction has been overlooked in scientific research. Our ability to navigate our chemical world through our sense of smell and taste plays a fundamental role in our survival, nutrition, and mental health. The number of patients facing the loss in their sense of smell and taste has set off a wave of research to better understand these impairments and develop therapeutic solutions. 

According to a study by Mullol et al., olfactory dysfunction is a common symptom that occurs in about 60% of cold and sinus infections, typically lasting 3-7 days. Impairments in our olfactory sense are estimated to cause 95% of gustatory dysfunctions, resulting in patients often experiencing both taste and smell loss. This is because taste and smell are intrinsically intertwined as both use chemoreceptors that allow us to navigate our chemical environment. When you take that sip of coffee, it releases chemicals that travel to the nose activating the olfactory receptors located in specialized neural cells. Synergistically, smell and taste chemoreceptors send signals to the brain that allow us to perceive flavor. Conversely, when impacted by upper airway viral infections or allergies that cause inflammation and obstruction, such as having a stuffy nose, this prevents the nasal chemoreceptors from receiving chemical signals, impairing our ability to smell and taste. What is interesting about the loss of smell and taste experienced by mild COVID-19 patients is that it can occur without the typical nasal congestion. A study composed of 417 patients with mild to moderate COVID-19 showed that 14.5% of patients without nasal obstruction or rhinorrhea (runny nose) presented either total or partial loss of their sense of smell (Lechien et al). This highlighted that SARS-CoV-2 may impact olfactory functions through other mechanisms.

A single-cell sequencing study conducted by researchers from Harvard University suggested that SARS-CoV-2 does not infect olfactory sensory neurons, but rather surrounding non-neural cell types. SARS-CoV-2 is known to use Angiotensin I Converting Enzyme 2 (ACE2) receptors found on the surface of cells to mediate entry. The single-cell sequencing results showed that the gene for the ACE2 receptor is not expressed in the olfactory sensory neurons, but rather in sustentacular and basal cells. Sustentacular cells are responsible for maintaining the integrity of the olfactory epithelium by providing metabolic and structural support for olfactory sensory neurons; similarly, basal cells are stem cells capable of regenerating the olfactory epithelium. Therefore, by disrupting the functions of these supporting cells, SARS-CoV-2 indirectly causes changes in olfactory sensory neurons that result in olfactory sensation loss.

As the virus clears out of the body, for many, these supporting cells are able to replenish and provide normal cellular functions for the olfactory neuron, enabling them to regain sensation. Nonetheless, nearly a year later, some have yet to recover their sense of smell and taste. This could be due to the impact of the virus being too extensive to allow the olfactory neural circuits to properly recover. This is a public health concern because there our olfactory sense serves as a natural alarm system. For example, the inability to detect spoiled food or smoke can expose someone to food poisoning or danger of fire, respectively. Additionally, not being able to enjoy the pleasures of flavors can cause poor appetite and undesired weight loss. Studies have shown that smell affects the mood quality of life as patients with olfactory and gustatory dysfunction have expressed experiencing depression and anxiety. For many who are regaining their sense of smell, they have had to relearn odors and rewire their olfactory neural circuits to recognize particular smells. Some treatments include platelet-rich plasma and beta-carotene supplements for nerve regeneration. However, there is still more research that needs to be done to find better therapeutic techniques to help patients restore the pleasures associated with perceiving odor and flavors.

References:

Agyeman, A. A., Chin, K. L., Landersdorfer, C. B., Liew, D., & Ofori-Asenso, R. (2020). Smell and taste dysfunction in patients with covid-19: A systematic review and meta-analysis. Mayo Clinic Proceedings, 95(8), 1621-1631. doi:10.1016/j.mayocp.2020.05.030

Lechien, J. R., Chiesa‐Estomba, C. M., Beckers, E., Mustin, V., Ducarme, M., Journe, F., . . . Saussez, S. (2021). Prevalence and 6‐month recovery of olfactory dysfunction: A Multicentre study of 1363 Covid‐19 patients. Journal of Internal Medicine. doi:10.1111/joim.13209

Marshall, M. (2021, January 14). COVID's toll on smell AND taste: What scientists do and don't know. Retrieved February 13, 2021, from https://www.nature.com/articles/d41586-021-00055-6

Mullol, J., Alobid, I., Mariño-Sánchez, F., Izquierdo-Domínguez, A., Marin, C., Klimek, L., . . . Liu, Z. (2020). The loss of smell and taste in the COVID-19 Outbreak: A tale of many countries. Current Allergy and Asthma Reports,20(10). doi:10.1007/s11882-020-00961-1

Samaranayake, L. P., Fakhruddin, K. S., & Panduwawala, C. (2020). Sudden onset, acute loss of taste and smell in CORONAVIRUS disease 2019 (COVID-19): A systematic review. Acta Odontologica Scandinavica, 78(6), 467-473. doi:10.1080/00016357.2020.1787505

Seladi-Schulman, J. (2020, October 12). Can a loss of taste and Smell be a symptom of COVID-19? Retrieved February 13, 2021, from https://www.healthline.com/health/coronavirus-loss-of-taste-loss-of-smell

Yan, C. H., Faraji, F., Prajapati, D. P., Ostrander, B. T., & DeConde, A. S. (2020). Self‐reported olfactory Loss associates with outpatient clinical course in COVID‐19. International Forum of Allergy & Rhinology,10(7), 821-831. doi:10.1002/alr.22592