Statistical analysis results
The means of the CCCRC and taste test scores of the different
subpopulations studied were analyzed with Student’s T test in order to
identify possible correlations between chemosensitive dysfunctions and
general or clinical patient characteristics. The results are shown in
Table 6 [Table 6]. No statistically significant correlations with
the sex of the patients nor with the severity of the pulmonary clinical
picture were found. On average, olfactory and gustatory scores were
worse in patients over 50 years of age. Anyway, this correlation was
statistically significant only for the taste (P = 0.003). Both the
olfactory (P = 0.000) and gustatory (P = 0.001) scores showed
statistically significant differences between subpopulations selected on
the basis of the time elapsed since the onset of symptoms.
DISCUSSION
After the recent spread of sars-cov-2 in Europe, several authors have
reported the high incidence of olfactory and gustatory dysfunctions in
COVID-19 patients [3-6]. Particularly, these symptoms appear to be
very common in the early stages of the disease [3] and sometimes
represent its only clinical manifestation [4]. The identification
and isolation of the paucisymptomatic patients is crucial for breaking
the virus chain of infection. However, all the reports published so far
do not evaluate quantitatively and qualitatively the extent of
chemosensory disorders in COVID-19 patients. In most cases the studies
are based on subjective self-evaluations of the patients, report of
anamnestic data or olfactory and gustatory questionnaire completion,
without any objective test or direct medical examination [4,5,6].
This can be explained by the emergency situation and the risk of
infection approaching these patients without proper personal protection
equipment.
This is the first study to objectively evaluate these symptoms. The
acquisition of objective data is fundamental to understand mechanisms of
olfactory and taste loss in coronavirus infections and might provide new
insights into aspects of viral pathogenesis.
The first and most important evidence of the present study is that
gustatory and olfactory dysfunctions are very frequent in COVID-19
patients. In our case series, 73.6% of patients reported having or
having had one or both of these problems during the course of the
infection. This frequency is much higher than that reported in the
anamnestic-observational studies of Vaira et al. [3] and Giacomelli
et al. [6], but similar to that found by Lechien et al. [5].
The analysis of the patient’s clinical course confirmed that ageusia and
anosmia are early symptoms in COVID-19, generally occurring within the
firsts 5 days of the clinical onset [Chart 1]. Indeed, in 13
patients of this series (18.1%), taste and smell impairment represented
the first clinical manifestation of the disease. Therefore,
otolaryngologists and head-neck surgeons should nowadays contemplate
SARS-CoV-2 infection in the differential diagnosis of these non-specific
chemosensitive disorders. Sudden onset within 24-48 hours and the
absence of nasal obstruction and rhinitic symptoms (in our case series
associated in only 9.1% of cases) are very suspect clinical features of
SARS-CoV-2 etiology.
In 66% of cases, the patient reported spontaneous regression of
chemoperceptive dysfunctions at the evaluation time. However, on
objective tests, 80% of these patients still revealed a certain degree
of residual hyposmia or hypogeusia. This contradiction could be linked
to the presence of a slight previous chronic alteration, in some cases,
or to the fact that the patient had noticed such a great improvement,
compared to the condition of ageusia and / or anosmia that he had
suffered, to consider his current chemopercective capacity as quite
normal.
The objective chemosensitive evaluation revealed mostly moderate and
mild hyposmia and hypogeusia [Table 4 and 5]. In general, the CCCRC
scores were more influenced by a widespread reduction of the olfactory
thresholds while the majority of patients, even with moderate and severe
hyposmia, maintained a good discriminative ability. Vicks-VapoRoub,
which also stimulates trigeminal olfactory sensitivity [7,8], was
correctly identified in 97.2% of cases. Further studies will be needed
to clarify the affection of one or both of the olfactory pathways by the
virus. As regards the gustatory function, the most affected
sensitivities were those for sweet (23 patients) and sour (21 patients),
but there was no clear predominance of disturbances towards a primary
taste in particular.
Although most patients reported having suffered complete ageusia and
anosmia, these pathological conditions were only detected in a few
patients during the tests. Generally, the evaluation was performed at an
advanced period of the clinical course (19.3 days from the clinical
onset, on average). An earlier evaluation, logistically difficult as the
patients in the first days after the diagnosis are uncommonly
hospitalized, would be very useful in order to study the olfactory and
gustatory functions when they are afflicted the most. In this regard, we
are collecting the data of an early evaluation multicenter protocol of
COVID-19+ patients quarantined at home, which will be subject to a
future publication.
The statistical analysis [Table 6] of the differences in
chemosensitive dysfunctions between selected subpopulations, has
highlighted some interesting aspects that should be confirmed on larger
case studies. Firstly, older patients reported lower CCCRC and taste
scores, with a statistically significant difference in taste. Obviously,
this data could be influenced by the aging processes that
physiologically cause a reduction in chemoperception [14].
The time elapsed since the clinical onset was detect to be the most
significantly related factor in taste (P = 0.001) and smell (P = 0.000)
alterations. This finding confirmed that the olfactory and gustatory
dysfunctions are typical symptoms of the early stages of the infection
and over time they tend to disappear or, at least, to decrease. It would
also be interesting to monitor these patients over time to establish the
long-term evolution of these disorders.
Finally, no significant correlation was detected between the extent of
the chemosensitive disorders and the severity of the pulmonary clinical
picture. This evidence, which must be confirmed by larger case studies,
could open up fascinating pathogenetic scenarios. The pathogenesis of
gustatory and olfactory dysfunctions is unclear and only hypotheses can
be made based on studies regarding other coronaviruses [15]. The
improvement of the chemoceptive function over time, would suggest a
competitive action of the virus on the receptors of the olfactory and
gustatory cells or local inflammatory phenomena, rather than permanent
cell damage. Assuming that, the viral load would certainly play an
important role in the pathogenesis of chemosensitive disorders. However,
considering that there is a correlation between the severity of the
systemic clinical picture and viral load [16], other local factors
are likely to partecipate in causing the onset of gustatory and
olfactory alterations in COVID-19 patients.
CONCLUSIONS
Olfactory and gustatory dysfunctions represent common clinical findings
in COVID-19 patients. Otolaryngologists and head-neck surgeons must by
now keep this diagnostic option in mind when evaluating cases of ageusia
and nonspecific anosmia that arose suddenly and are not associated with
rhinitis symptoms. The evaluation presented in this study allows to
quantify the extent of these disorders by providing an objective and
standardized basis that enable to evaluate functional recovery over
time. Further studies are needed to investigate more in depth, from a
clinical and pathogenetic point of view, chemosensitive disorders in
COVID-19 patients.
FUNDING
None declared
CONFLICT OF INTEREST
None of the authors has a financial interest in any of the products,
devices or drugs mentioned in this manuscript.
ACNOWLEDGEMENT
The authors would like to thank all the Italian health workers for the
effort and all the sacrifices they are making during this serious health
crisis.
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