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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