Discussion:
The involvement of COVID-19 in the development of olfactory and
gustatory dysfunctions seems obvious. However, the characterization of
the pathophysiological mechanisms underlying the olfactory dysfunction
remains challenging regarding the risk of contamination. In this study,
we have performed both subjective and objective olfactory evaluations in
COVID-19 patients through online patient-reported outcome questionnaires
and individual objective psychophysical testings. Interestingly, 38% of
patients with self-reported olfactory dysfunction had normal olfactory
testing at the sniffin’stick test.
The mismatch between the self-reported loss of smell and the anosmia
regarding psychophysical testings has already been suggested in a recent
Italian study where a few COVID-19 patients, who self-reported loss of
smell, were objectively anosmic.14 Thus, the
prevalence of olfactory dysfunction related to COVID-19 would be
overestimated in the epidemiological studies where the loss of smell was
based on subjective reports.
Another important finding of this study is the non-significant
relationship between symptoms of nasal inflammation and objective
olfactory dysfunction. In most cases of olfactory dysfunction occurring
in viral infections, the olfactory disorder is related to the
inflammatory reaction of the mucosa, leading to nasal obstruction,
rhinorrhea and postnasal drip. In some cases, the olfactory dysfunction
appeared to be related to other mechanisms, such as a neural spread of
the virus into the neuroepithelium and the olfactory bulb. In 2007,
Suzuki et al . demonstrated that coronavirus may be detected in
the nasal discharge of patients with olfactory
dysfunction.15 In this study, some patients had normal
acoustic rhinometry, suggesting that nasal inflammation and related
obstruction were not the only etiological factors underlying the
olfactory dysfunction in viral infection. Netland et al .
demonstrated on transgenic mice expressing the SARS-CoV receptor (human
angiotensinconverting enzyme 2) that SARS-CoV may enter the brain
through the olfactory bulb, leading to rapid transneuronal
spread.16 The neurotropism of the COVID-19 is not new
and would be associated with other symptoms and findings. For example,
the virus spread into the central nervous system is currently suspected
to play a key role in respiratory failure through an effect on the
medullary cardiorespiratory center.17 Similarly, the
existence of different patterns of gustatory and olfactory recoveries
would be explained by selective neurological
impairments.1 In other words, and suggested by the
aroma and gustatory outcomes, the loss of taste would be not a
retro-olfactory disorder in some patients. Future experimental and
clinical studies are needed to better understand the pathophysiological
mechanisms underlying the development of olfactory and gustatory
dysfunctions. These studies would associate patient-reported outcome
questionnaires, psychophysical olfactory evaluations, fiberoptic
examinations, and imaging or neurophysiological assessments.
The main limitation of the present study is the heterogeneity between
patients about the duration of the olfactory dysfunction. However, it is
complicated to recruit patients at the first day of the olfactory
disorder for many reasons. First, many patients have other troublesome
symptoms (e.g. fatigue, myalgia, arthralgia), which may limit the
realization of the tests. Second, the recruitment of patients at the
first day of the olfactory dysfunction involved a continuous
communication to recruit these patients. In practice, it is complicated
to communicate with the general public every day for a scientific study.
The lack of full objective methods to assess olfaction may be considered
as another weakness. In this study, we decided to use the Identification
sniffin’sticks test (16 items) for practical and ethical reasons. This
test may be performed quickly, which is important to reduce the risk of
potential contamination of caregivers.