Is loss of smell an early diagnostic indicator of COVID-19?

Evelina Thunell, Asifa Majid and Johan N. Lundström

Recent studies suggest that loss of the sense of smell is an early symptom of COVID-19 (Gane et al., 2020; Lechien et al., 2020). Researchers at King’s College London collected data from over 1.5 million individuals using a mobile app where people noted their symptoms. Out of the 579 people who were confirmed to have COVID-19, 59% reported anosmia (loss of smell) or ageusia (loss of taste) (Menni et al., 2020). These symptoms appeared around 24-72 hours before more typical symptoms, such as fever (Menni et al., 2020; Vaira et al., 2020). Another recent self-report study conducted in Iran showed that around 30% of participants experienced anosmia. They also found that reported COVID-19 rates in a region was highly correlated with new documented cases of anosmia (Bagheri et al., 2020).

Building on this research, the Global Consortium for Chemosensory Research has created an online survey, available in 30 languages, to collect further data. These studies are important because they suggest that loss of smell may be an early indicator of SARS-CoV-2 infection. If confirmed, this would allow potentially infected individuals to isolate themselves at an early stage to avoid further spread. This could be particularly effective in countries where access to other diagnostic tools is limited. 

Psychologists have played a crucial role in understanding and developing tests that assess the sense of smell and taste since the 19th century, when researchers such as Gustav Fechner and Hermann von Helmholtz first began to systematically map the relationship between physical stimuli and sensory perception. Today, the vibrant field of research in the chemical senses spans diverse psychological approaches from neuroimaging to cross-cultural field studies. Against this backdrop, the current data positing a link between COVID-19 and the sense of smell and taste require critical appraisal.

Recent studies are based on self-report, and as such suffer from two main issues. First, true ageusia is extremely rare and often when people report loss of taste, they are actually suffering from loss of smell. This confusion is due to the fact that the sense of smell is largely responsible for flavour perception (Lundström et al., 2011), but lay people are not aware of this leading to erroneous reports of taste loss. Second, people’s self-reported ability to smell is only loosely connected to their actual ability (Landis et al., 2003). This means that more objective means of testing the sense of smell are required. Efforts are underway: a 5-minute self-administered smell assessment test which uses common household products has been launched (Snitz et al., 2019; details at https://smelltracker.org), with a view to establishing whether the results of self-administered olfactory tests are a reliable indication of SARS-CoV-2 infection. 

Despite the shortcomings of the studies mentioned above, it is reasonable to assume that there is a true link between anosmia and COVID-19. Several independent reports all reach similar conclusions, and other corona viruses can cause loss of smell. Upper airway virus infections, such as flu or cold, cause around 30% of all cases of anosmia, and some of these viruses belong to the corona virus family (Seiden, 2004). There are important differences, however, between the anosmia caused by SARS-CoV-2 and the typical virus induced anosmia. First, unlike other viruses, young people and women are more prone to develop anosmia due to SARS-CoV-2. Second, the typical build-up of mucus in the nasal cavity is absent. Finally, the progression is rapid and often unaccompanied by other symptoms (Gane et al., 2020; Lechien et al., 2020). 

Two possible mechanisms for SARS-CoV-2 induced anosmia have been proposed. First, a preprint study indicates that ACE2 receptors, which corona viruses are known to bind to, are ubiquitous in both the lungs and the olfactory epithelium, and that SARS-COV-2 can damage existing olfactory receptor cells as well as stem cells and other supporting mechanisms (Brann et al., 2020). Second, many viruses, including corona viruses, can propagate via the olfactory nerve and thereby infect and damage the olfactory bulb (Schwob et al., 2001; Wheeler et al,, 2017). Corona virus RNA has been found in olfactory areas of the brain (Li et al., 2020), and a preprint study reports that some COVID-19 patients display neurological symptoms (Mao et al., 2020). Further research will be needed to confirm the validity of these proposed mechanisms, and there are potentially longer-term psychological effects of this virus still to be understood. 

Finally, while initial reports indicate that a sizable portion of COVID-19 positive individuals develop anosmia, spontaneous recovery is the norm for virus-induced anosmia. Even though some animal data indicates that other corona viruses can destroy the olfactory bulb (Schwob et al., 2001), so far there are no reports of long-lasting effects in humans. If the sense of smell has not returned a few weeks after recovery, there is a simple behavioural intervention that people can implement: an effective treatment is olfactory training. By simply attempting to smell and identify odours a few times a day over several weeks, people can improve their sense of smell (Damm et al., 2014).  

Evelina Thunell, Karolinska Institute, Sweden, and Purdue University, USA

Asifa Majid, University of York, UK

Johan N. Lundström, Karolinska Institute, Sweden, Monell Chemical Senses Center and University of Pennsylvania, USA

See also 'The knowing nose' and 'The essence of the human condition'

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