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
REFERENCES
[1] Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia:
common findings in COVID-19 patients. Laryngoscope. 2020. Doi:
10.1002/lary.28692.
[2] Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in
COVID-19 infection. A novel syndrome? Rhinology. 2020. Doi:
10.4193/Rhin20.114.
[3] Lechien JR, Chiesta-Estomba CM, De Siati DR et al. Olfactory and
gustatory dysfunctions as a clinical presentation of mild-to-moderate
forms of the coronavirus disease (COVID-19): a multicenter European
study. Eur Arch Otorynolaryngol. 2020. Doi: 10.1007/s00405-020-05965-1
[4] Giacomelli A, Pezzati L, Conti F et al. Self-reported olfactory
and taste disorders in SARS-CoV-2 patients: a cross-sectional study.
Clin Infect Dis. 2020 Doi: 10.1093/cid/ciaa330.
[5] Hopkins C, Surda P, Kumar BN. Presentation of new onset anosmia
during COVID-19 pandemic. Rhinology. 2020; Doi:https://doi.org/10.4193/Rhin20.116.
[6] Dory RL. Psychopysical testing of smell and taste function.
Handb Clin Neurol. 2019;164:229-46.
[7] Spotten LE, Corish CA, Lorton CM et al. Subjective and objective
taste and smell changes in cancer. Ann Oncol. 2017;28:969-84.
[8] Nagata Y. Measurement of odor threshold by triangle odor bag
method. Odor Measurement Review. 2003;118:118-27.
[9] Massarelli O, Vaira LA, Biglio A, Gobbi R, Dell’aversana Orabona
G, De Riu G. Sensory recovery of myomucosal flap oral cavity
reconstructions. Head Neck. 2018;40:467-74.
[10] Pingel J, Ostwald J, Pau HW, Hummel T, Just T. Normative data
for a solution-based taste test. Eur Arch Otorhinolaryngol.
2010;267:1911-7.
[11] Hwang CS, Kim JW, Al Sharhan SS, Kim JW, YOON JH, Kim CH.
Development of a gustatory function test for clinical application in
Koerean subjects. Yonsei Med J. 2018;59:325-30.
[12] Cain WS, Gent, J, Catalanotto FA, Goodspeed RB. Clinical
evaluation of olfaction. Am J Otolaryngol. 1983;4:252-6.
[13] Cain WS, Gent JF, Goodspeed RB, Leonard G. Evaluation of
olfactory dysfunction in the Connecticut Chemosensory Clinical Research
Center. Laryngoscope. 1988;98:83-8.
[14] Leon EA, Catalanotto FA, Werning JW. Retronasal and orthonasal
olfactory ability after laryngectomy. Arch Otolaryngol Head Neck Surg.
2007;133:32-6.
[15] Aksoy C, Elsurer C, Artaç H, Bozkurt MK. Evaluation of
olfactory function in children with seasonal allergic rhinitis and its
correlation with acoustic rhinometry. Int J Ped Otorhinolaryngol.
2018;113:188-91.
[16] Veyseller B, Ozucer B, Karaaltin AB, Yildirim Y, Degirmenci N,
Aksoy F, Ozturan O. Connecticut (CCCRC) olfactory test: normative values
in 426 healthy volunteers. Indian J Otolaryngol Head Neck Surg.
2014;66:31-4.
[17] Vaira LA, Deiana G, Fois AG et al. Objective evaluation of
anosmia and ageusia in COVID-19 patients: a single-center experience on
72 cases. Head Neck. 2020. Doi: 10.1002/HED.26204
TABLE LEGEND