By Daniel Erenstein, Neurobiology, Physiology & Behavior ‘21

Author’s Note: Last spring, I enrolled in the inaugural offering of the University Writing Program’s wine writing course. Our instructor, Dr. Alison Bright, encouraged us to report on topics of personal interest through our news stories on the wine industry, viticulture, enology, and more. In this article, which was prepared for an audience of general science enthusiasts, I examine how biologists are making sense of a puzzling COVID-19 symptom — anosmia, or loss of smell — and what COVID-19 patients with this condition can do to overcome it. Eighteen months into this pandemic, scientists continue to study cases of COVID-19-related anosmia with dreams of a treatment on the horizon. I hope that readers feel inspired by this article to follow this in-progress scientific story. I extend my appreciation to Dr. Bright, who throughout the quarter shared approaches to rhetorical awareness that elevated my grasp of effective writing.

Image caption: Anton Ego, the “Grim Eater” from PIXAR’s Ratatouille, is reminded of his childhood by Remy’s rendition of ratatouille, a Provençal dish of stewed vegetables.

With a single bite of Remy’s latest culinary creation, the eyes of Anton Ego, a notoriously harsh food critic, dilate, and Ratatouille’s viewers are transported back in time with Monsieur Ego. The meal — a simple yet elegant serving of ratatouille, accompanied by a glass of 1947 Château Cheval Blanc — has triggered a flashback to one singular moment, a home-cooked meal during his childhood. The universal charm of this enduring scene resonates; in Ego’s eyes, many recognize how our senses of smell and taste can impact a culinary experience. 

Imagine how a real-life version of this scene might change for the millions of COVID-19 patients who have lost their sense of smell [1]. Anosmia, the phenomenon of smell loss, has become one of the more perplexing COVID-19 symptoms since first observed in patients during the earliest months of the pandemic [2].

What happens when we lose our sense of smell? During the pandemic, scientists have studied smell loss, which affects more than 85 percent of COVID-19 patients according to research published this year in the Journal of Internal Medicine [3]. In fact, anosmia is so common in COVID-19 patients that physicians were offered guidance for testing olfactory function as an indicator of infection last year [4]. 

To simplify studies of these complicated senses, taste and smell are often examined independently of one another, even though these senses are usually experienced simultaneously.

“Smell is just — it’s so crucial to taste, which means it’s really crucial to everything that I do,” said Tejal Rao, a New York Times food critic, in a March episode of The Daily [5]. “And it’s really difficult to cook without a sense of smell if you’re not used to it. You don’t know what’s going on. It’s almost like wearing a blindfold.”

Rao, who lost her sense of smell in mid-January after contracting COVID-19, began to search for answers to this mystery from scientists. Rao’s journey started with TikTok “miracle cures” and other aromatherapies — unfortunately, they were too good to be true — but she eventually discovered the work of Dr. Pamela Dalton, a scientist at the Monell Chemical Senses Center in Philadelphia [6]. At the center, Dalton studies the emotions that are triggered by our sense of smell [7].

During simple colds or viral infections, smell is normally affected when the molecules in food and other aromas are physically blocked off from chemoreceptors in our nose by congestion. Scientists have also cited Alzheimer’s and Parkinson’s diseases, head trauma, and chemotherapy as triggers for anosmia [8]. But a separate phenomenon was occurring in the case of COVID-19.

“COVID is different in that way, because most people who lost their sense of smell did so without having any nasal congestion whatsoever,” Dalton told Rao during an interview.

One study published in October of last year by Dr. Nicolas Meunier, a French neuroscientist, aimed to investigate how the SARS-CoV-2 virus, which causes COVID-19, may disrupt sustentacular cells [9]. These structural cells express the ACE2 receptor, which the virus hijacks to gain entry into our cells, at higher levels [10]. Sustentacular cells support the specialized neurons that transmit signals from the nose to the brain.

When Meunier and his team at Paris-Saclay University in France infected hamsters with the virus, tiny hair-like projections known as cilia on the surfaces of olfactory neurons began to peel back from sustentacular cells. This disruption is a possible explanation for the difficulties with smell that COVID-19 patients experience. 

If it is true that damage to sustentacular cells causes anosmia, loss of smell is not an irreversible brain condition. In this case, the poor connection between incoming odors and brain networks that typically process these stimuli is at fault, not direct damage to the brain itself. The sudden onset of smell loss in COVID-19 patients supports this thinking.

“It was just like a light bulb got turned off or a switch got flicked to off,” Dalton said. “And one moment they could smell. And the next moment, nothing smelled.”

But because olfactory support cells regularly regenerate, this loss of smell is only temporary, which allows for retraining of our senses. Two months of smell training, also known as olfactory training, allowed Rao to regain her sense of smell.

Olfactory training gradually exposes patients to particularly strong smells. Spices such as cinnamon or cumin, for example, were perfect for Rao’s first smell training session [5], and AbScent, a British charity offering support to patients with anosmia, sells kits with rose, lemon, and eucalyptus [8]. Scientists have found that recurring exposure to these strong scents gives the brain time to recalibrate its networks, a feature known as neuroplasticity [11].

But “you don’t just go from hurt to healed overnight,” Rao said. “It’s more like adjusting and learning how to live in a new space. That’s really just the beginning.”

Our chemical senses have the power to satisfy, to inspire, even to cause our memory to reveal itself, as 20th-century French author Marcel Proust observed in his seven-volume novel À la recherche du temps perdu, or In Search of Lost Time. Researchers have even speculated that our sense of smell can facilitate learning in other sensory domains, including vision [12].

While scientists further investigate how coronavirus causes loss of smell, olfactory training can provide an avenue in the meantime for COVID-19 patients to recover this crucial sense. Indeed, many patients are “in search of lost time,” and smell training can help them to once again experience food and wine in its sensory entirety.

References:

1. Allen J, Almukhtar S, Aufrichtig A, Barnard A, Bloch M, Cahalan S, Cai W, Calderone J, Collins K, Conlen M, et al. 2021. Coronavirus in the U.S.: Latest Map and Case Count. New York (NY): New York Times; [accessed 28 July 2021]. https://www.nytimes.com/interactive/2021/us/covid-cases.html.
2. Symptoms of COVID-19. 2021. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Division of Viral Diseases; [accessed 28 July 2021]. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.
3. Lechien JR, Chiesa-Estomba CM, Beckers E, Mustin V, Ducarme M, Journe F, Marchant A, Jouffe L, Barillari MR, Cammaroto G, et al. 2021. Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients. J Intern Med. 290(2):451–461. https://doi.org/10.1111/joim.13209.
4. Whitcroft KL, Hummel T. 2020. Olfactory Dysfunction in COVID-19: Diagnosis and Management. JAMA. 323(24):2512–2514. https://doi.org/10.1001/jama.2020.8391.
5. Antolini T, Dorr W, Powell D, Schreppel C. 2021. A Food Critic Loses Her Sense of Smell. New York (NY): New York Times; [accessed 28 July 2021]. https://www.nytimes.com/2021/03/23/podcasts/the-daily/coronavirus-smell-food.html.
6. Rao T. 2021. Will Fish Sauce and Charred Oranges Return the World Covid Took From Me? New York (NY): New York Times; [accessed 28 July 2021]. https://www.nytimes.com/2021/03/02/dining/covid-loss-of-smell.html.
7. What COVID 19 is teaching us about the importance of smell, with Pamela Dalton, PhD. 17 Mar 2021, 33:31 minutes. American Psychological Association; [accessed 28 July 2021]. https://youtu.be/0pG_U13XDog.
8. Schoch D. 2021. Distorted, Bizarre Food Smells Haunt Covid Survivors. New York (NY): New York Times; [accessed 28 July 2021]. https://www.nytimes.com/2021/06/15/health/covid-smells-food.html
9. Bryche B, St Albin A, Murri S, Lacôte S, Pulido C, Ar Gouilh M, Lesellier S, Servat A, Wasniewski M, Picard-Meyer E, et al. 2020. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun. 89(2):579–586. https://doi.org/10.1016/j.bbi.2020.06.032.
10. Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou HJ, Fletcher RB, et al. 2020. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 6(31): eabc5801.
11. Kollndorfer K, Kowalczyk K, Hoche E, Mueller CA, Pollak M, Trattnig S, Schöpf V. 2014. Recovery of Olfactory Function Induces Neuroplasticity Effects in Patients with Smell Loss. Neural Plast. 1–7. https://doi.org/10.1155/2014/140419.
12. Olofsson JK, Ekström I, Lindström J, Syrjänen E, Stigsdotter-Neely A, Nyberg L, Jonsson S, Larsson M. 2020. Smell-Based Memory Training: Evidence of Olfactory Learning and Transfer to the Visual Domain. Chem Senses. 45(7):593–600. https://doi.org/10.1093/chemse/bjaa049.