Statistical analysis
Statistical analysis was performed using SPSS 26.0 (IBM, Armonk, NY, USA). Categorical variables are reported in numerals and percentages of the total. Descriptive statistics for quantitative variables are given as the mean ± standard deviation (SD). Statistical analysis of score differences reported by the patients in the two evaluations was performed by Wilcoxon signed-rank test for paired data. The level of statistical significance was set at P ≤ 0.05 with a 95% confidence interval.
RESULTS
The study population included 33 COVID-19 patients (11 males, 22 females, mean age 51.8 years old) followed by the Security and Prevention Departments of the University Hospital of Sassari, University Hospital of Salerno and Bologna Maggiore-Bellaria Hospital. Table 4 provides a framework summary of patient general and clinical features [Table 4].
During the course of the infection, current or regressed chemosensitive dysfunctions were reported by 21 patients (63.6%). In detail, 13 patients (39.4%) reported combined gustatory and olfactory disorders. Four patients (12.1%) presented isolated reduction in taste, while isolated hypo/anosmia was reported in other 4 patients (12.1%). At the time of the telephone evaluation, 11 out of 21 patients (52.4%) reported complete regression of chemosensitive symptoms.
Anamnestically, 17 patients (51.5%) reported having or having had olfactory disorders during infection, including 13 cases of anosmia and 4 cases of hyposmia. Both the self-administered test and that performed by the operator showed normosmia in 8 patients, various degree hyposmia in 21 patients and complete anosmia in 4 cases. Compared to the CCCRC test, the telephone evaluation revealed more cases of moderate hyposmia (13 vs 9) and fewer of mild hyposmia (5 vs 9) [Chart 1].
Of the 17 patients (51.5%) who complained gustatory dysfunction, 10 reported ageusia, 4 hypogeusia and 2 dysgeusia. The results of the telephone and outpatient evaluations are shown in chart 2 [Chart 2].
The olfactory (P = 0.201) and taste (P = 0.180) scores did not report any significant statistical difference between the self- and operator-administered evaluations [Table 5].
DISCUSSION
Early identification and isolation of infected patients is the most important therapeutic strategy for slowing the spread of SARS-CoV-2. It is therefore necessary to establish which are the most frequent symptoms in the initial and paucisymptomatic forms of COVID-19. In the first days of April we reported the high rates of olfactory and gustatory disturbances in these patients [1]. In the last two weeks, several other authors have reported the same clinical finding [2-5].
Recently, we were the first to objectively analyze the chemoreceptive functions in hospitalized COVID-19 patients, confirming that these disturbances appear commonly in the first days of the infection and in paucisymptomatic cases [17]. A functional evaluation in these early stages of the disease would be very useful, to objectively establish the real incidence and extent of chemosensitive symptoms, but it is difficult to carry it out for at least two orders of reasons. First, these patients are generally not hospitalized and perform the evaluation at home is logistically impossible during the health crisis that we are facing. Secondly, in literature there are no psychophysiological or instrumental tests that can be remotely administered.
The tests we used in this study were created on the basis of already validated and widely used olfactory and gustatory evaluation protocols [9-16]. The scoring system was established so that the results of the two tests would be comparable.
The rates of taste and smell dysfunction during the infection (63.6%) in the present case series were consistent with those of our previous analysis on hospitalized patients [17]. The differences between the results of the two tests were statistically insignificant, both for taste and olfaction. In general, non-blind patients remotely evaluated by telephone tend to underestimate the olfactory threshold. They tend to report perception for more diluted solutions. This bias is partially compensated by a tendency to obtain lower discriminative scores, due to the different evaluation mechanisms of the two tests. In fact, the patient-administered tests provide a quantitative assessment (from 1 to 10) of perception while the operator-administered tests provide a mere qualitative answer to forced identification choice. In this way, for example, even a patient with a mild or moderate hyposmia or hypogeusia could still be able to identify all the odors or tastes obtaining the maximum score on the outpatient tests. The score would instead be sub-normal if we asked the patient to quantitatively evaluate the extent of perception and not only his presence or absence. Overall, the results of the statistical analysis attest to the validity of auto-administered chemosensitive evaluation protocol.
Some possible limitations must however be mentioned. First, the study cohort was composed only of infected health personnel. Therefore, it was not a representative sample of the general population. The evaluated subjects were highly compliant for such a complex test, it is possible that the reliability of the test will decrease by extending enrollment to the general population, especially if elderly patients. For this reasons, the inclusion criteria should be carefully evaluated, limiting the assessment to very compliant subjects. Secondly, the self-administered test has proven to be very accurate in identifying patients with complete anosmia or ageusia, severe hyposmia and hypogeusia and in cases of normal chemopercective functions. On the other hand, it tends to underestimate some cases of moderate hyposmia and hypogeusia, downgrading them to mild forms [Chart 1, Chart 2]. Due to the logistical problems already reported, in this validation study, patients were evaluated in advanced stages of the clinical course (20.1 days from clinical onset, on average). For this reason, in many cases the chemosensitive disorder was already resolved and the severity of the residual dysfunction was very variable. On the basis of what has been reported by patients, it is reasonable to think that objective evaluation at an earlier stage would detect more serious or complete dysfunctions or, on the contrary, no functional alterations, rather than intermediate disturbances. In the early stages the test should be even more accurate.
CONCLUSIONS
Based on the results of this study on quarantined patients, the olfactory and gustatory evaluation by self-administered test can be considered a valid tool, fundamental for remotely obtaining qualitative and quantitative data on the extent of chemosensitive disorders. These data could lead to early detection and isolation of paucisymptomatic COVID-19 cases.
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 None declared
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