key: cord-255941-uc6z0vuu
authors: Desai, Mauli; Oppenheimer, John
title: “The Importance of Considering Olfactory Dysfunction During the COVID-19 Pandemic and in Clinical Practice”
date: 2020-10-28
journal: J Allergy Clin Immunol Pract
DOI: 10.1016/j.jaip.2020.10.036
sha: 
doc_id: 255941
cord_uid: uc6z0vuu

The emergence of a worldwide pandemic due to coronavirus disease 2019 (COVID-19) and frequent reports of smell loss in COVID-19 infected patients has brought new attention to this very important sense. Data is emerging that smell impairment is a prominent symptom in COVID-19 and that this coronavirus behaves differently in causing olfactory dysfunction compared to other respiratory viruses. Anosmia and hyposmia, the complete and partial loss of smell, respectively, can result from many causes, most commonly from viral infections, sinonasal disease, and head trauma. Olfactory dysfunction negatively impacts quality of life, as sense of smell is important for flavor perception and the enjoyment of food. Olfaction is also important for the detection of warning smells, such as smoke, natural gas leaks, and spoiled food. Allergists and immunologists frequently encounter anosmia and hyposmia in patients with severe chronic rhinosinusitis with nasal polyps, and will likely see more infection-induced olfactory dysfunction in the era of COVID-19. Therefore, now more than ever, is crucial that we understand this impairment, how to evaluate and how to measure it. In this review, we offer a clinically relevant primer for the allergist and immunologist on olfactory dysfunction subtypes, exploring the pathophysiology, appropriate clinical assessment, objective smell testing, and management. We will also focus on the emerging literature on COVID-19 olfactory dysfunction, its unique features, and its important implications for this pandemic.

Globally, as of August 15th 2020, more than 20 million confirmed cases of coronavirus disease 59 2019 (COVID-19) have been reported to the World Health Organization (WHO).(1) Early in the 60 global pandemic, evidence emerged that many people with COVID-19 present with loss of smell 61 and/or taste. In response, the CDC added new loss of smell or taste to its list of key symptoms 62 of COVID-19, which includes cough, shortness of breath or difficulty breathing, fever, chills, 63 muscle pain, and sore throat.(2) Importantly, anosmia or hyposmia may be indicative of 64 COVID-19 infection, even in the absence of other symptoms. Data are emerging that COVID-19 65 olfactory dysfunction (OD) has distinct features from typical viral-induced OD, both in its 66 prevalence and clinical characteristics, and is an area of active investigation. For patients with 67 complete anosmia, many of whom have never experienced loss of smell before, anosmia can be a 68 disturbing symptom that disrupts their enjoyment of food, with many of them asking their 69 physician "will I be able to smell again?" 70 71 Beyond COVID-19, allergist and immunologists see OD frequently in patients with chronic 72 rhinosinusitis (CRS), and in particular, in patients with CRS with nasal polyps (CRSwNP). 73

Treatment paradigms for CRSwNP have shifted with the approval of dupilumab for the treatment 74 of refractory nasal polyps, and will likely expand given that several additional biologics are in 75 the pipeline. With expansion of the treatment armamentarium, many patients who were 76 previously primarily managed by ear, nose, and throat (ENT) doctors are now being referred to 77 allergists and immunologists for medical management and follow-up. Therefore, it is crucial that 78 allergists and immunologists have a good working knowledge of OD; this will help them 79 evaluate clinical symptoms and therapeutic efficacy when starting biologics and other treatments. 80

We suspect this important sense is likely underappreciated by allergists, as the mechanics of 81 olfaction, differential diagnosis, and quantitative smell testing are not routine parts of fellowship 82 training curricula. 83 84 DEFINITIONS 85 OD is defined as the reduced or distorted ability to smell (orthonasal olfaction) or reduced or 86 absent flavor perceptions when eating (retronasal olfaction). Impairment may be sudden in onset 87 or gradual, and may be temporary or permanent. Symptoms may be constant in nature, or 88 fluctuate in severity; these characteristics can provide clues to the underlying etiology of disease. 89

There may also be associated dysgeusia (also known as parageusia), which is distortion in the 90 quality of taste. Table 1 Lower prevalence has been noted when based on self-report alone, suggesting some patients may 105 be poor perceivers of smell dysfunction.(3) In addition, it is not uncommon for patients to report 106 a problem with taste, when actually their taste is intact and what they are experiencing is a loss 107 of sense of smell that is impacting flavor perception. This is due to the complex experience of 108 smell, taste, and flavor, and underscores the importance of objective testing, which will be 109 discussed later in this review. 110

Smell 113

Olfaction is one of the body's five basic senses (alongside sight, hearing, taste, and touch). 114

These senses send information to the brain to help us perceive the world. Olfaction occurs via 115 the sensory olfactory system, as shown in Figure 1 sour, salty, and bitter. There is also a fifth taste, umami (7) but it is more difficult to test for, due 128 to its complexity. Taste mainly occurs through taste buds on the tongue while eating. Flavor 129 perception is a complex, multisensory experience which involves the chemical senses of smell, 130 taste, and chemical irritation. The aroma of foods is an important contributor to flavor. OD (anosmia, hyposmia) is emerging as a key symptom of COVID-19. Its prevalence is not yet 173 known, but reports suggest it is common, and occurs across a spectrum of disease severity. 174

Notably, it may be present in individuals who are otherwise minimally symptomatic or 175 asymptomatic. It may also be the sole presenting symptom and is typically sudden in onset. 176

Several medical organizations suggest that new-onset OD during the pandemic may be used as a 177 warning flag to suggest appropriate testing and quarantine to prevent infectious spread, and use 178 of appropriate personal protective equipment (PPE) in health care workers evaluating these 179 patients. (12) 180 181 It is too soon to fully elucidate the clinical features of COVID-19 OD. There is suggestion that it 182 may be a subtype of OD different than the typical viral (common cold)-induced OD. Emerging 183 literature suggest patients with COVID-19 OD typically lack associated sinonasal complaints 184 (such as nasal congestion, rhinorrhea, post nasal drip).(13) One small study by Huart et al. 185 shows the impairment to be more severe in COVID-19 AOD and that there may be a 186 concomitant taste disturbance. This study compared 10 COVID-19 patients with 10 acute cold 187 patients and 10 healthy controls using chemosensory testing. (13) 

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