I can no longer stand the smell of smoked salmon

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Journal Identiﬁcation = NRP Article Identiﬁcation = 0636 Date: June 16, 2021 Time: 4:21 pm

doi:10.1684/nrp.2021.0636

REVUE DE NEUROPSYCHOLOGIE

NEUROSCIENCES COGNITIVES ET CLINIQUES

64 Point of view

Rev Neuropsychol

2020 ; 12 (S1) : 64-6

I can no longer stand the smell

of smoked salmon

Je ne supporte plus l’odeur du saumon fumé

Anne-Marie Ergis

EA 4468«Maladie d’Alzheimer:

marqueurs génétiques et vasculaires, neuropsychologie», Institut de Psychologie, Université de Paris,

71 avenue Edouard-Vaillant, 92100 Boulogne-Billancourt, France

<anne-marie.ergis@u-paris.fr>

To cite this article: Ergis AM. I can no longer stand the smell of smoked salmon.Rev Neuropsychol2020;12(S1):64- 6 doi:10.1684/nrp.2021.0636

Foreword

A week after my return from a mission to French Guyana at the end of February 2020, I started to cough – a dry cough – and to suffer from severe headaches. I put it all down to the fatigue due to jet lag, and the heat shock that had no doubt made me catch cold. Then other symptoms appeared. About ten days after my ﬁrst symptoms, I realized that I could no longer stand the smell of smoked salmon:

I could smell a foul smell, like a sewer. This disturbing but fortunately transient episode prompted me to research COVID-19-related dysosmias.

Introduction

At the start of the COVID-19 pandemic, the most frequently described symptoms were headache, muscle pain, severe fatigue, followed by fever and respiratory signs (dry cough, chest pain, breathing difﬁculties), often a few days after the ﬁrst symptoms. Subsequently, other clinical signs were described, and their list has grown as knowledge about SARS-Cov-2 progresses [1]. Some of these signs suggest damage to the central nervous system: headaches, dizziness, convulsions, cerebrovascular accidents (stroke), changes in consciousness, hemiplegia in the Wuhan cohort; agitation, confusion, disorders of executive functions in patients admitted to intensive care at the Strasbourg University Hospital; meningitis described in Japan; encephalitis; lastly, the sudden loss of smell

∗This article is an English language translation of the following article:

Ergis AM. Je ne supporte plus l’odeur du saumon fumé. Rev Neuropsychol2020 ; 12 (2) : 184-6 doi:10.1684/nrp.2020.0566.

Correspondence:

A.-M. Ergis

(anosmia) and/or taste (ageusia), which could be minor neurological manifestations of COVID-19.

Olfaction

Olfaction – or smell – is the sense that enables animals to perceive and analyze odors, that is, the volatile chemicals present in the air. We have two other systems (or so-called chemical senses) that allow us, in addition to the olfactory system, to perceive and interpret this information: taste and the trigeminal nerve (more speciﬁcally its branch called the mandibular nerve). Taste allows us to recognize sweet, bit- ter, sour, salty tastes and glutamate (also called umami, a term borrowed from Japanese). The trigeminal nerve relays information that contributes to taste sensations such as men- thol, which acts on thermoreceptors, or capsaicin in chilli, which acts on pain receptors. All other chemical information is perceived and identiﬁed by olfaction[2]. Olfactory perception begins at the level of the olfactory epithelium.

A smell activates a combination of receptors, which gen- erates action potentials via axons that pass through the riddled lamina of the ethmoid bone. These axons make synapses with the olfactory bulb, which projects to the pri- mary olfactory cortex, located in the temporal lobe, then to the secondary olfactory cortex, located in the orbitofrontal cortex[3]. The perception of odors is inﬂuenced by our past experiences, so the more familiar a smell, the easier it will be to distinguish it from others.

When we eat, the odorous molecules pass from the oral cavity to the nasal cavity by the retronasal route, which often leads to confusion between taste and olfaction. What is often described as the ﬂavor of a food is actually the information returned by olfaction (retronasal) and not by taste. This is why patients with anosmia without ageusia also feel a loss of ﬂavor perception, and think they have lost

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65 Point of view

both taste and smell, whereas in fact they have lost only smell[2].

Olfaction disorders or dysosmias

Olfaction plays a very important role in many aspects of daily life: it is a source of sensory and food pleasure, and its loss can be a danger (for example not detecting the smell of burning or of gas), can cause a decrease in the pleasure of eating, generate a feeling of insecurity about one’s own body odors, modify our social relationships, and can lead some patients to develop depression. From a clinical point of view, dysosmias are described in terms of quantitative and qualitative disorders. They are thought to affect around 15% of the population[2].

Quantitative disorders

Anosmia is the total loss of smell, while hyposmia is deﬁned by a decrease in the ability to smell. Hyperosmia, on the other hand, is an exacerbation of the sense of smell. Pres- byosmia refers to the progressive decrease in smell related to age[4]. They can be measured using psychophysical tests [3].

Qualitative disorders

Parosmias are distortions of olfactory stimuli that are present in the patient’s environment. They are classically represented by an odor (e.g. smoked salmon) perceived as a different odor, generally unpleasant (e.g. sewer).

Cacosmia is the perception of an unpleasant odor, of infectious dento-sinus origin or related to gastroesophageal reﬂux[5]. In contrast, euosmia, which is much rarer, cor- responds to an unpleasant odor perceived as pleasant [6]. Phantosmia (or olfactory hallucination) is the perception of an odor in the absence of chemical stimuli in the patient’s environment. It is observed in neurosen- sory (epilepsy, brain tumors, migraine aura) or psychiatric pathologies.

Qualitative odor disorders are rarer than quantitative disorders. They are generally explored by means of ques- tionnaires, but it has recently become possible to carry out investigations by means of functional magnetic resonance techniques[7].

Dysosmias can be temporary and disappear sponta- neously within a few days or weeks, or be longer-lasting.

Transient dysosmias most often occur in the context of an upper respiratory tract infection (URI), usually rhinosinusitis, or an allergy. Long-lasting dysosmias can set in following a complication of rhinosinusitis, most often chronic, of post-infectious origin, or else can be post-traumatic, idio- pathic, or more rarely of congenital origin. Others are disorders secondary to neurological disease (Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, etc.), to a systemic or metabolic disease or to a brain tumor (see[2]).

In 2005, Bonﬁlset al. studied a cohort of 56 patients who complained of parosmias that had existed for 3 months to 22 years[8]. In all patients, quantitative disturbances (anosmia, hyposmia) preceded parosmia, associated mainly with URI. The odors perceived were most often rotting, sewage and burning odors.

Olfaction disorders and COVID-19

It was in March 2020 that new clinical signs began to be described by clinicians, especially in Europe: digestive signs, and olfactory disorders. It quickly became clear that anosmia, with or without ageusia, was a common symptom of COVID-19. Doctors, initially mainly ENT specialists, reported the existence of numerous cases that received extensive media coverage of anosmia in patients with suspected or confirmed Covid-19. The National Institute of Excellence in Health and Social Services of Que- bec (INESSS) published on March 31, 2020 a report on sudden severe anosmia and loss of taste without nasal obstruction [9]. This report summarized data and information disseminated by ENT specialists and infectious disease specialists from several countries around the world (France, United Kingdom, United States, Canada, Iran, Germany, South Korea), before publication. In patients infected with SARS-Cov-2, anosmia appears suddenly without nasal obstruction, and sometimes accompanied by ageusia. It can occur without inflammation, fever, or a cough, which are the most common symptoms of infection. These symptoms had not yet been described in Asia, but are now the subject of publications. Experts even suggest that these symptoms could help differentiate COVID-19 from seasonal flu. We will only present here a limited number of publications representative of current research.

Faced with numerous ENT reports from all over Europe, the Young Otolaryngologists of the International Federation of Otorhinolaryngology Societies (YO-IFOS) launched an international epidemiological study to characterize olfactory and taste disorders in infected patients. In a preliminary study of 417 patients recruited from 12 European hospitals, and presenting mild to moderate symptoms of COVID-19, Lechien and colleagues observed that 85.6% of patients presented with dysosmia related to the condition. Among them, 79.6% had anosmia, 20.4% a hyposmia, 32.4% a parosmia, and 12.6% a phantosmia, and ﬁnally 88% presented an ageusia[10].

The interest of this study is that qualitative dysosmias were also explored, while in most of the others, patients were interviewed and tested only for anosmia or hyposmia. Other observations from studies carried out in other countries (Italy, Iran, etc.) also point to anosmia being more frequent in young patients, and in women. On the other hand, Chinese authors have reported cases of dysosmia much less frequently [11]. According to Lechien et al.,

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66 Point of view

these dysosmias could be minor neurological manifestations. The anosmia could come from lesions of the cells surrounding the olfactory neurons, suggesting that the olfactory bulb is then a gateway for the virus to the brain. In a new study that included 1,420 patients recruited from 12 European hospitals, Lechien and colleagues observed that symptoms varied by age and gender, with younger patients more often presenting with odor disturbances than older ones. Anosmia, headache, nasal obstruction and fatigue were more common in women [12]. Anosmia was a key symptom in patients with mild to moderate COVID-19 and was not associated with nasal obstruction or rhinorrhea as in the preliminary study [10]. Finally, according to the authors, the fact that dysosmias have been little described in Chinese studies is perhaps linked to the fact that the majority of patients were hospitalized with more severe forms of the disease. It could also be linked to the polymorphism of the expression of the angiotensin 2 converting enzyme ACE2 (the SARS-CoV-2 virus uses this receptor to attach itself and enter the cells of its host in order to multiply in human tissues), as differences appear to exist in its expression levels between Asian and European populations.

Conclusion

Only revealed in March 2020, dysosmias following infection with SARS-CoV-2 have become an important marker of Covid-19, that is useful in distinguishing between this disease and inﬂuenza. These symptoms are now recognized by the WHO. In addition, these dysosmias are speciﬁc, as they are not associated with rhinorrhea.

They seem to indicate damage to the central nervous system, although the physiopathological mechanisms are still poorly understood. Among different hypotheses, some researchers suggest that the mechanism leading to anosmia could be neurological: the virus, from the nasal cavity, could migrate via the olfactory nerves to certain brain regions involved in the processing of olfactory information and perhaps even breathing control [12]. Other researchers are interested in the ACE2 receptor, expressed by cells of the lungs, heart, kidneys and intestines, but also by neurons and glial cells in the brain[13].

Conﬂict of interest None.

References

1.https://www.pasteur.fr/fr/centre-medical/ﬁches-maladies/maladie- covid-19-nouveau-coronavirus.

2.Landis BN. Les troubles de l’odorat. Rev Med Suisse 2007 ; 3 : 32571.

3.Wen Hsieh J, Landis BN. Tests psychophysiques de l’olfaction : Quoi de neuf ?Rev Med Suisse2018 ; 14 : 1746-50.

4.Goncalves S, Goldstein BJ. Pathophysiology of Olfactory Disorders and Potential Treatment Strategies. Curr Otorhinolaryngol Rep2016 ; 4 : 115-21.

5.Magnavita N. Cacosmia in healthy workers. Br J Med Psychol 2001 ; 74 : 121-7.

6.Landis BN, Frasnelli J, Hummel T. Euosmia: A rare form of parosmia.

Acta Otolaryngol (Stockh.)2006 ; 126 : 101-3.

7.Rombaux P, Huart C, Mouraux A. Physiologie et exploration des troubles de l’olfaction. Traité d’Oto-rhino-laryngologie 2016 ; 11.(3).

8.Bonﬁls P, Avan P, Faulcon P, Malinvaud D. Distorted Odor- ant Perception. Arch Otolaryngol Head Neck Surg 2005 ; 131 : 107-12.

9.Institut national d’excellence en santé et en services sociaux (INESSS). Covid-19 et anosmie sévère brutale et perte de goût sans obstruction nasale. Québec (Qc) : INESSS, 2020.

10.Lechien JR, Chiesa-Estomba CM, De Siati DR,et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (Covid-19) : A multicenter European study.Eur Arch Otorhinolaryngol2020. doi : 10.1007/s00405-020r- r05965-1.

11.Mao L, Wang M, Chen S, et al. Neurological manifestations of hospitalized patients with Covid-19 in Wuhan, China: A ret- rospective case series study. MedRXiv 2020. doi : https ://doi.org/

10.1101/2020.02.22.20026500.

12.Lechien JR, Chiesa-Estomba CM, Place S, et al. Clinical and Epidemiological Characteristics of 1,420 European Patients with mild- to-moderate Coronavirus Disease 2019. J Intern Med 2020. doi : 10.1111/joim.13089. AOP.

13.Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the Covid-19 Virus Targeting the CNS : Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chemical Neuroscience 2020 ; 11 : 995-8.