\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Objective evaluation of anosmia and ageusia in~ COVID-19 patients: a
single-center experience on 72 cases.~~~~~~~~~~~~}



\author[1]{Luigi Angelo Vaira, MD}%
\affil[1]{University Hospital of Sassari, }%


\vspace{-1em}



  
  \date{May 15, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
\emph{Background.} The firsts European case series are detecting a very
high frequency of chemosensitive disorders in COVID-19 patients, ranging
between 19.4\% and 88\%.{}\emph{Methods.} Olfactory and gustatory
function was objectively tested in 72 COVID-19 patients treated at
University Hospital of Sassari.\emph{Results} Overall, 73.6\% of the
patients reported having or having had chemosensitive disorders.
Olfactory assessment showed variable degree hyposmia in 60 cases and
anosmia in 2 patients. Gustatory assessment revealed hypogeusia in 33
cases and complete ageusia in 1 patient. Statistically significant
differences in chemosensitive recovery were detected based on age and
distance from the onset of clinical manifestations.\emph{Conclusion.}
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%
\end{abstract}%



\sloppy




Luigi Angelo Vaira\textsuperscript{1}, MD; Giovanna
Deiana\textsuperscript{2}, MD; Alessandro Giuseppe
Fois\textsuperscript{3}, MD; Pietro Pirina\textsuperscript{3}, MD;
Giordano Madeddu\textsuperscript{4}, MD; Andrea De
Vito\textsuperscript{4}, MD; Sergio Babudieri\textsuperscript{4}, MD;
Marzia Petrocelli\textsuperscript{5}, MD; Antonello
Serra\textsuperscript{6}, MD; Francesco Bussu\textsuperscript{7}, MD;
Enrica Ligas\textsuperscript{1} MSN, RN; Giovanni
Salzano\textsuperscript{8}, MD; Giacomo De Riu\textsuperscript{1} MD,
FEBOMFS.

~

\textsuperscript{1} Maxillofacial Surgery Operative Unit, University
Hospital of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

\textsuperscript{2} Department of Medical, Surgical and Experimental
Sciences, University of Sassari, Viale San Pietro, 07100 Sassari, Italy.

\textsuperscript{3} Respiratory Diseases Operative Unit, University
Hospital of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

\textsuperscript{4} Infectious Diseases Operative Unit, University
Hospital of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

\textsuperscript{5} Maxillofacial Surgery Operative Unit; Bellaria and
Maggiore Hospital, AUSL Bologna, Italy.

\textsuperscript{6} Surveillance and Prevention Department, University
Hospital of Sassari, Via Matteotti 58, 07100 Sassari, Italy.

\textsuperscript{7} Otolaryngology Operative Unit, University Hospital
of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

\textsuperscript{8} Maxillofacial Surgery Unit, University Hospital of
Naples ``Federico II'', Via Pansini 5, 80131 Naples, Italy.

\textbf{*Corresponding Author:}{}

Luigi Angelo Vaira

Viale San Pietro 43/B

e-mail: luigi.vaira@gmail.com~

tel.: +393401846168

fax: +39079229002

\textbf{~}

\textbf{Keywords:} COVID-19; anosmia; ageusia; gustatory function;
olfactory function.

\textbf{Abstract}

\emph{Background.} The firsts European case series are detecting a very
high frequency of chemosensitive disorders in COVID-19 patients, ranging
between 19.4\% and 88\%.{}

\emph{Methods.} Olfactory and gustatory function was objectively tested
in 72 COVID-19 patients treated at University Hospital of Sassari.

\emph{Results} Overall, 73.6\% of the patients reported having or having
had chemosensitive disorders. Olfactory assessment showed variable
degree hyposmia in 60 cases and anosmia in 2 patients. Gustatory
assessment revealed hypogeusia in 33 cases and complete ageusia in 1
patient. Statistically significant differences in chemosensitive
recovery were detected based on age and distance from the onset of
clinical manifestations.

\emph{Conclusion.} 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{}

\textbf{INTRODUCTION}

~The rapid spread of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) {[}1{]} is enabling researchers worldwide to acquire a
large amount of clinical data regarding coronavirus disease (COVID-19).
The serious health emergency situation makes data collection and
analysis very difficult, but some important clinical differences are
starting to emerge between Chinese and European case series.

Particularly, smell and taste dysfunctions have been reported as
uncommon by Chinese colleagues, during COVID-19 infection. In the only
paper present in literature, Mao et al. {[}2{]}, analyzing neurological
manifestation frequency in 214 infected patients, found out anosmia in
11 (5.1\%) and ageusia in 12 (5.6\%) cases.

In contrast to these data, the firsts European case series {[}3-6{]} are
detecting a very high frequency of chemosensitive disorders in COVID-19
patients, ranging between 19.4\% and 88\%. In particular, the olfactory
and gustative alterations seem especially frequent in the initial stages
of the infection and in paucisymptomatic patients {[}3-5{]}. These
complaints could represent, therefore, pivotal symptoms suspecting
SARS-CoV-2 infection {[}3{]}.

However, all the studies published up to now are
anamnestic-observational, presenting the limitation of not reporting any
systematic sensitive evaluation of the patients. The objective
assessment is fundamental, quantifying the extent of the dysfunction and
monitoring the recovery over time.

The purpose of this study is to objectively evaluate the gustatory and
olfactory function, through the use of psycho-physiological objective
tests, in COVID-19 patients treated in the University Hospital of
Sassari.

\textbf{MATERIALS AND METHODS}

~The study was conducted on SARS-CoV-2 positive patients, treated by the
COVID departments (Pneumology, Infectious Disease and Surveillance and
Prevention Operative Units) of the University Hospital of Sassari,
between March 31 and April 6, 2020.

To be enrolled in the study, patients had to meet the following
inclusion criteria: adults over 18 years of age, rhino-pharyngeal swab
positive for SARS-CoV-2 infection, patient acceptance for participation
in the study.

On the contrary, the study exclusion criteria were: uncooperative
patients, assisted ventilation, psychiatric or neurological disorders,
previous surgery or radiotherapy in the oral and nasal cavities,
pre-existing manifestation of smell and taste alterations, history of
head trauma, allergic rhinitis, chronic rhinosinusitis and psychiatric
or neurological disorders.

All patients provided informed consent for participation in the study.
The study protocol was approved by an independent ethics committee (n\selectlanguage{ngerman}°
378-2020-OSS-AUSLBO).

\emph{\textbf{Clinical record assessment}}

Some general information were recorded for all the patients: age,
gender, praevious clinical history and swab positivity. COVID-19 signs
and symptoms were detected from clinical records.

The patients were carefully asked in order to obtain a conceivable
timeline of the onset, lasting and the eventual regression, of the
chemosensitive symptoms.

\textbf{}\emph{\textbf{Olfactory function assessment}}

Both the olfactory threshold and the odor discriminative ability were
assessed. All tests were conducted in a quiet room, by the same
operators. Olfactory function assessment was carried out by means of the
Connecticut Chemosensory Clinical Research Center orthonasal olfaction
test (CCCRC) {[}7-11{]}. The CCCRC is a simple, validated and widely
used test, that includes a butanol threshold assessment and an odor
identification test using common odors.

Threshold testing was performed presenting solutions of N-bunatol in
deionized waters, decreasing concentration in 8 steps. The strongest
butanol concentration was 4\% in 60 mL of deionized water (bottle 0).
Each other bottle (from 1 to 8) contained a subsequent 1:3 N-butanol
dilution. Two identical squeezable bottles were presented to the
patient: one containing the N-butanol solution, Starting from the major
dilution, and the other filled with deionized water. The patient was
then asked to close one nostril and squeeze the bottle immediately below
the other, reporting which of the two bottles smelled most. The
threshold was identified when the subject gave the correct answer 4
times. In case of error, the next most concentrated solution was given
to the patient. The threshold was quantified for each of the two
nostrils with a score from 0 to 8 corresponding to less concentrated
bottle that the patient was able to correctly detect. The average
between values of the two nostrils expressed the overall score.

For the identification test, common odorants, familiar to the Italian
population {[}Table 1{]}, were placed inside 180 mL opaque jars covered
with gauze. One at a time, the samples were presented to the patient in
the same way as the threshold test. Therefore, the patient was asked to
identify the odorant on a list containing the 10 test items and 10
distractors {[}Table 1{]}. Score ranged from 0 to 10 and was obtained
from the average of the two nostrils.

The threshold and identification test scores, after being analyzed
separately, were finally converted into the CCCRC composite score. The
scoring system is shown in table 2 {[}Table 2{]}.

\textbf{}\emph{\textbf{Gustatory function assessment}}

A standardized and validated test, which investigates the ability to
perceive four primary tastes (sweet, salty, sour and bitter) was used to
evaluate the gustatory function {[}12,13{]}. Four solutions, one for
each primary taste, were prepared as follows:

\begin{itemize}
\tightlist
\item
  Salted solution: 30 g of table salt were added to 1 liter of deionized
  water.
\item
  Sweet solution: 30 g of refined sugar were dissolved in 1 liter of
  deionized water.
\item
  Sour solution: 90 mL of commercial 100\% lemon juice added to 1 liter
  of deionized water.
\item
  Bitter solution: unsweetened decaffeinated coffee.
\end{itemize}

Deionized water was used as control. During the trial, 1 ml of each
solution was dropped onto the center of the patient tongue. A different
cotton swab was used for each of the solutions and then disposed. The
patient was then asked to indicate whether the perceived flavor was
sweet, salty, bitter, acid or neutral. The solutions were presented in a
random order, excluding the bitter taste, which was always presented
last because it tends to alter subsequent taste perception {[}12{]}.

The answers were recorded as either correct or incorrect. Taste score
ranged from 0 to 4 allowing to classify the patients into four
categories: Normal (score 4), mild hypogeusia (score 3), moderate
hypogeusia (score 2), severe hypogeusia (score 1) and ageusia (score 0).

\textbf{}\emph{\textbf{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). The statistical analysis of
differences in olfactory and gustatory function, between population
subgroups, was performed using Student's T test. The level of
statistical significance was set at P \selectlanguage{english}[?] 0.05 with a 95\% confidence
interval.

\textbf{RESULTS}

Following the inclusion and exclusion criteria, 72 COVID-19 patients (27
males, 45 females, mean age 49.2 years old) were enrolled for the study
at the University Hospital of Sassari. Of these, 3 were hospitalized in
the Respiratory Diseases Department, 22 in the Infectious Diseases
Department, and the remaining 47 patients belonged to the infected
healthcare personnel, were quarantined at home and assisted by the
Surveillance and Prevention Department. The last group was assessed in
occasion of the first recall for the control swab. Table 3 reports a
framework summary of patient general characteristics and clinical
features {[}Table 3{]}.

Fifty-three patients (73.6\% of the study population) reported having
chemosensory dysfunctions during the course of the COVID-19. Especially,
isolated taste disorders were reported in 9 cases (12.5\%), while 14
patients (14.4\%) reported isolated olfactory dysfunctions. Thirty
patients (41.7\%) reported they experienced combined disorders of both
olfaction and taste. At the time of the evaluation, most of these
patients (35 cases, 66\%) reported a complete recovery of chemosensitive
functions, which occurred in less than 5 days in 19 cases and in more
than 5 days in the remaining 16. On the contrary, 18 patients (34\%)
reported a persistence of alterations in taste and olfaction.

\textbf{}\emph{\textbf{Olfactory function assessment results}}

Overall, 44 patients (61.1\%) reported having or having had olfactory
disorders during SARS-CoV-2 infection. The alterations reported include
complete anosmia (34 patients), hyposmia (8 patients) and disosmia (2
patients). Table 4 summarizes the olfactory function assessment results
{[}Table 4{]}. At the time of the examination, based on the CCCRC scores
obtained, complete anosmia was detected in 2 cases (2.8\%), 58 patients
presented variable degree hyposmia (80.6\%) while in 12 cases (16.7\%)
the olfactory function was normal. Twenty-eight patients, who
subjectively reported complete olfactory recovery, discordantly
presented mild (18 cases) or moderate (10) hyposmia in the CCCRC test.

\emph{\textbf{Gustatory function assessment}}

Thirty-nine patients presented, or had presented before the check, taste
disorders, subjectively completely resolved in 8 cases. The reported
alterations included complete ageusia (28 patients) and variable
severity of hypogeusia (11 cases) associated with dysgeusia in 7
patients. Table 5 provides a framework summary of the olfactory function
assessment results {[}Table 5{]}. Ageusia was detected in 1 patient
(1.4\%), severe hypogeusia in 7 patients (9.7\%), moderate hypogeusia in
11 patients (15.3\%) and mild hypogeusia in 16 patients (22.2\%).
Differently, 37 patients (51.4\%) presented a normal gustatory function
by correctly identifying all 4 primary tastes.

\emph{\textbf{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.

\textbf{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.

\textbf{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.

\textbf{FUNDING}

None declared

\textbf{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.

\textbf{REFERENCES}

{[}1{]} Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian
JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L,
Holmes EC, Zhang YZ. A new coronavirus associated with human respiratory
disease in China. Nature. 2020;579:265-9.

{[}2{]} Mao L, Wang M, Chen S. He Q. Chang J, Hong C, Zhou Y, Wang D,
Yanan Li, Huijuan J, Hu B. Neurological manifestations of hospitalized
patients with COVID-19 in Wuhan, China: a retrospective case series
study. MedRXiv.\emph{https://doi.org/10.1101/2020.02.22.200.26500}.

{[}3{]} 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.

{[}4{]} Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in
COVID-19 infection. A novel syndrome? Rhinology. 2020. Doi:
10.4193/Rhin20.114.

{[}5{]} Lechien JR, Chiesta-Estomba CM, De Siati DR, Horoi M, Le Bon SD,
Rodriguez A, Dequanter A, Dequanter D, Blecic S, El Afia F, Distinguin
L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne
P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C,
Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, RIs L, Lovato A, De
Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and
gustatory dysfunctions as a clinical presentation of mild-to-moderate
forms of the coronavirus disease (COVID-19): a multicenter European
study.

{[}6{]} Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Orelni
L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli
M. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a
cross-sectional study. Clin Infect Dis. 2020 Doi: 10.1093/cid/ciaa330.

{[}7{]} Cain WS, Gent, J, Catalanotto FA, Goodspeed RB. Clinical
evaluation of olfaction. Am J Otolaryngol. 1983;4:252-6.

{[}8{]} Cain WS, Gent JF, Goodspeed RB, Leonard G. Evaluation of
olfactory dysfunction in the Connecticut Chemosensory Clinical Research
Center. Laryngoscope. 1988;98:83-8.

{[}9{]} Leon EA, Catalanotto FA, Werning JW. Retronasal and orthonasal
olfactory ability after laryngectomy. Arch Otolaryngol Head Neck Surg.
2007;133:32-6.

{[}10{]} Aksoy C, Elsurer C, Artac 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.

{[}11{]} 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.

{[}12{]} 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.

{[}13{]} Loewen IJ, Boliek CA, Harris J, Seikaly H, Rieger JM. Oral
sensation and function: a comparison of patients with innervated radial
forearm free flap reconstruction to healthy matched controls. Head Neck.
2010;32:85-95

{[}14{]} Doty RL. Age-related deficits in taste and smell. Otolaryngol
Clin North Am. 2018;51:815-25.

{[}15{]} Vaira LA, Salzano G, Piombino P, De Riu G. Pathogenesis of
ageusia and anosmia in COVID-19 patients: a literature review. 2020
(Manuscript submitted for publication)

{[}16{]} Liu Y, Yang Y, Zhang C, Huang F, Wang D,Yuan J, Wang Z, Li J,
Li J, Feng C, Zhang Z, Wang L, Peng L, Chen L, Quin Y, Zhao D, Tan S,
Yin L, Xu J, Zhou C, Jiang C, Liu L. Clinical and biochemical indexes
from 2019-nCoV infected patients linked to viral loads and lung injury.
Sci China Life Sci. 2020;63:364-74.

TABLE LEGEND

\par\null

\textbf{Hosted file}

\verb`HED-20-0524_Table_1.docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 1. Identification test 20 item list {[}7,8{]}

\textbf{Hosted file}

\verb`HED-20-0524_Table_2.docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 2. Connecticut Chemosensory Clinical Research Center (CCCRC) test
composite scoring

system {[}7{]}.

\textbf{Hosted file}

\verb`HED-20-0524_Table_3.docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 3. General and clinical characteristics of the study population

\textbf{Hosted file}

\verb`HED-20-0524_Table_4 (1).docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 4. Connecticut Chemosensory Clinical Research Center (CCCRC) test
results

\textbf{Hosted file}

\verb`HED-20-0524_Table_5.docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 5. Gustatory function assessment results

\textbf{Hosted file}

\verb`HED-20-0524_Table_6.docx`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Table 6. Statistical analysis results

\par\null

CHART LEGEND

\par\null

\textbf{Hosted file}

\verb`HED-20-0524_Chart_1.jpg`  available at \url{https://authorea.com/users/312328/articles/443262-objective-evaluation-of-anosmia-and-ageusia-in-covid-19-patients-a-single-center-experience-on-72-cases}

Chart 1. Olfactory and gustatory dysfunction clinical course.

\selectlanguage{english}
\FloatBarrier
\end{document}

