As many as one in three COVID-19 patients report smell loss as an early symptom of the infection.
Researchers say the loss of smell could be used as a key clinical indicator of infection in otherwise symptom-free or pre-symptomatic carriers of coronavirus.
Medical experts in countries hit by COVID-19 are reporting the first tell-tale signs of the virus may be in an unexpected loss of smell.
Ear, nose, and throat (ENT) surgeons say loss of smell, as the virus causes swelling in the olfactory mucosa more than other viruses, could be used as a key clinical indicator in otherwise symptom-free carriers of COVID-19.
“It is these ‘silent carriers’ who may remain undetected by current screening procedures, which may explain why the disease has progressed so rapidly in so many countries around the world,” says South Australian specialist Flinders University Professor Simon Carney, from the Southern ENT and Adelaide Sinus Centre.
“While further research is required, loss of smell, or anosmia, has been reported in as many as one in three patients in South Korea and, in Germany, this figure was as high as two in three patients,” says Professor of Otolaryngology (head and neck surgery) at Flinders University.
“An ENT professor in London has reported seeing a dramatic increase in patients with anosmia as their only symptom of COVID-19 infection.”
As Australia struggles to contain the spread of COVID-10, the identification of these carriers could help to slow the spread of infection.
“In the UK, ENT surgeons are pushing to have anosmia highlighted as an important symptom that may signify a patient may be an asymptomatic carrier,” says Professor Carney, immediate past president of the Australia and New Zealand Rhinologic Society.
Doctors and COVID-19 detection centres could use this subtle sign and unexplained sudden anosmia the testing criteria, he says. The image is in the public domain.
“Australia is in a position to take advantage of these findings overseas to try and ‘flatten the curve’ while we still can.”
Doctors and COVID-19 detection centers could use this subtle sign and unexplained sudden anosmia the testing criteria, he says.
Patients should also consider calling their GP with this early symptom as a precursor for possible treatment..
Smell accounts for 95% to 99% of chemosensation; while, taste accounts for the rest of chemosensation. Anosmia is the inability to perceive smell/odor. It can be temporary or permanent and acquired or congenital.
There are many causes. For example, any mechanical blockage preventing odors from reaching the olfactory nerves can cause the loss of sense of smell. This blockage can be due to inflammatory processes like simple infections causing mucus plugs or nasal polyps. Neurological causes can include disturbances to the sensory nerves that make up the olfactory bulb or anywhere along the path in which the signal of smell is transferred to the brain.
To better understand this process, it is helpful to understand how people can perceive smell. When a particle with odorant molecules in the air is present, it travels up through the nasal canals to the nasal cavity, where olfactory receptor neurons extend from the olfactory bulb that sits on the cribriform plate of the brain.
Each nasal cavity contains about 5 million receptor cells or neurons. There are 500 to 1000 different odor-binding proteins on the surface of these olfactory receptor cells. Each olfactory receptor cell expresses only one type of binding protein.
These afferent olfactory neurons (cranial nerve I) facilitates the transfer of a chemical signal (particles in the air) to an electrical signal (sensed by afferent receptor neurons) which is then transferred and ultimately perceived by the brain.
From the olfactory bulb, the signal is further processed by several other structures of the brain, including the piriform cortex, entorhinal cortex, amygdala, and hippocampus. Any blockage or destruction of the pathway along which smell is transferred and processed may result in anosmia.
Anosmia in the ENT clinic—examination, diagnosis, and prognosis
Anosmia can result from many underlying diseases. The most common causes are sinonasal diseases, postinfectious disorder, and post-traumatic disorder (Damm et al. 2004; Nordin and Brämerson 2008).
Other etiologies (e.g., congenital, idiopathic, toxic disorders, or disorders caused by a neurodegenerative disease) are less common but nonetheless important to rule out. In a patient suffering from an olfactory disorder, the first stage of the diagnosis is the patient’s medical history.
The clinician should evaluate how the disorder started, for example, suddenly, after a trauma or a (severe) cold, which then makes a post-traumatic disorder or a disorder after an upper respiratory tract infection (post-URTI), very likely.
Conversely, if the patient has difficulties recalling the exact moment the disorder began and describes olfactory fluctuations, sinonasal disorders can be assumed. A gradual onset and difficulties in recalling a triggering event also might suggest age-related, idiopathic disorder, or disorder due to a neurodegenerative disease.
In contrast to patients with sinonasal disorders, patients suffering from neurodegenerative diseases also describe the smell loss as either “gradually diminishing” or as “gone” but rarely as fluctuating.
Moreover, the patient has to be asked whether he/she remembers any olfactory function at all to rule out a congenital disorder. Intake of medications has to be evaluated as well as preceding operations or toxic exposures, for example, in a work environment.
A thorough ENT examination (for guidelines, see Figure 2) for olfactory disorders should include nasal endoscopy to visualize the olfactory cleft and to rule out any visual endonasal pathology. Special care is taken to notice septal deviation, tumors, and signs of acute or chronic sinonasal disease such as secretion, crusts, and polyps (Welge-Luessen et al. 2014).
Testing of olfactory function using a validated and standardized test is mandatory because subjective ratings of olfactory function are not always reliable (as described above; Wehling et al. 2011; Adams et al. 2016).
Depending on cultural background, olfactory testing is usually performed using, for example, the UPSIT (Doty, Shaman, Applebaum, et al. 1984) or the Sniffin Sticks test battery (Hummel et al. 1997) or any other validated test. Recording of olfactory-evoked potentials is possible but usually not performed routinely even though it is often applied in medico-legal cases (Hummel and Welge-Luessen 2006).
The endonasal findings in postinfectious disorders, in disorders related to age, to neurodegenerative diseases or to trauma are usually without any pathology. If needed, additional imaging (computer tomography or magnetic resonance imaging) can be performed.
The volume of the olfactory bulb (OB) can be used to predict prognosis of the olfactory dysfunction (Rombaux et al. 2012). Therapies for olfactory dysfunction should match the etiology of the disorder.
In sinonasal disorders, therapy consists of steroids, either topical or systemic. Topical steroids so far have only been proven to be effective in allergic rhinitis (Stuck et al. 2003), especially if applied in combination with an antihistamine such as azelastinhydrochloride as provided in the trademarked AzeFlu spray (Klimek et al. 2017).
However, if drops are used, the correct application of drops to reach the olfactory cleft is crucial and has to be instructed: in a head-down forward position (Benninger et al. 2004; Scheibe et al. 2008, but see also Mori et al. 2016).
In sinonasal disorders, peroral steroids have been proven to be effective (Jafek et al. 1987; Banglawala et al. 2014), even though both duration and dose of the applied steroids shows great variation and remains controversial.
Importantly, even though not often encountered by otorhinolaryngologists, side effects of steroids such as osteonecrosis have to be considered (Dilisio 2014). Surgical therapy in form of functional endoscopic sinus surgery might improve some cases of olfactory dysfunction.
The rationale behind this is to improve ventilation and thus to decrease inflammation in the area of the olfactory cleft which is likely to contribute to the presence of the disorder (Yee et al. 2010).
Nevertheless, because it is very difficult to predict if olfactory function will improve with the surgery, conservative treatment in cases of chronic rhinosinusitis with polyps is recommended (Rimmer et al. 2014).
Several attempts have been undertaken to identify factors predicting surgical outcome and success rate in regard to olfactory function. To date, no histologic factors have been identified to predict postoperative outcome (Soler et al. 2010; Nguyen et al. 2015); previous sinus operations (Nguyen et al. 2015) and the existence of an aspirin-exacerbated respiratory disease (Katotomichelakis et al. 2009) lower the chance of postoperative olfactory restoration.
In post-URTI disorders, spontaneous recovery is observed in 32–66% of patients (Philpott and DeVere 2014). Different therapeutic approaches have been reported to support the spontaneous regeneration.
Smell training, first described by Hummel et al. (2009), seems to be the most effective one. Smell training sets consist of four different odorants that have to be sniffed intensely twice a day for several seconds each over a period of at least 4 months.
Its effect has been confirmed in a large multicenter cross-over study (Damm et al. 2014) as well as by a recent meta-analyses (Pekala et al. 2016; Sorokowska et al. 2017), and it seems to be even more effective when a variety of odorants are rotated over time and training is prolonged (Altundag et al. 2015).
Application of vitamin A nose drops might be of additional benefit but has to be proven yet, whereas peroral application of vitamin A did not improve olfactory function (Reden et al. 2012). Application of intranasal citrate might also be of benefit to these patients (Whitcroft et al. 2016).
Spontaneous recovery rates in post-traumatic olfactory disorders takes place in a much lower percentage of patients probably due to post-traumatic scarring in the area of the lamina cribrosa, accompanied by intracranial lesions (Lotsch et al. 2015) and shearing injuries.
Attempts have been undertaken to improve olfactory outcome by applying steroids, either perorally (Jiang et al. 2010) or intraseptally (Fujii et al. 2002), which have been shown to improve olfactory function in animal models (Kobayashi and Costanzo 2009).
However, both studies included only a small number of patients with large variation, no controls, and reported only limited effects. On the other hand, ZincGluconat, either alone or in combination with peroral steroids, improved olfactory function compared with spontaneous recovery or steroid treatment (Jiang et al. 2015).
Smell training, as described above, can be offered in post-traumatic disorders and Parkinson’s disease with some potential improvement in olfactory function (Haehner et al. 2013; Konstantinidis et al. 2013).
Further studies with larger numbers of patients are needed to prove the clinical significance of treatments for individuals suffering from olfactory dysfunction related to sinonasal disease, upper respiratory tract infection, and post-trauma. No proven therapy exists for age-related smell loss or idiopathic smell loss.