10.14639/0392-100X-suppl.1-42-2022-03
Only a few studies have assessed smell and taste in Coronavirus Disease 2019 (COVID-19) patients with psychophysical tests, while the majority performed self-rating evaluations. Given the heterogeneity of the published literature, the aim of this review was to systemati- cally analyse the articles on this topic with a focus on psychophysical testing. A search on PubMed and Web of Science from December 2019, to November 2021, with cross-refer- ences, was executed. The main eligibility criteria were English-language articles, investi- gating the clinical features of olfaction and gustation in COVID-19 patients using self-rat- ing assessment, psychophysical testing and imaging techniques. A total of 638 articles were identified and 66 were included. Self-rating assessment was performed in 31 studies, while psychophysical testing in 30 and imaging techniques in 5. The prevalence of chemosensory dysfunction was the most investigated topic, followed by the recovery time. About the psy- chophysical assessment, the extended version of the Sniffin’ Sticks was used in 11 articles and the Connecticut Chemosensory Clinical Research Center test in another 11. The olfac- tory threshold performance was the most impacted compared to the discrimination and identification capacities in accordance with the hypothesis of a tropism of SARS-CoV-2 for the olfactory mucosa. The timing significantly influenced the results of the psychophysical testing with 20% of patients presenting olfactory dysfunction at one month after infection.
text/xml
1827-675X
2107
en
Matteo Gelardi
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
infections
Results from psychophysical tests of smell and taste during the course of SARS-CoV-2 infection: a review
Text.Serial.Journal
https://www.actaitalica.it/
42
Annual congress report
2022-04-26
2022-04-06
2022-04-28
2022-04-28
S20-S35
1
Matteo Gelardi
2022/04/26
10.14639/0392-100X-suppl.1-42-2022-03
S20
Department of Otorhinolaryngology, University Hospital of Foggia, Foggia, Italy
1827-675X
infections
S35
Results from psychophysical tests of smell and taste during the course of SARS-CoV-2 infection: a review
https://www.actaitalica.it/article/download/2107/766
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42(SUPPL.1):S20-S35; doi: 10.14639/0392-100X-suppl.1-42-2022-03




Results from psychophysical tests of smell and taste
during the course of SARS-CoV-2 infection: a review
Risultati dei test psicofisici olfattivi e gustativi durante l’infezione COVID-19:
revisione della letteratura
Eleonora M.C. Trecca1,2, Michele Cassano1, Francesco Longo2, Paolo Petrone3, Cesare Miani4, Thomas Hummel5,
Matteo Gelardi1
1
  Department of Otorhinolaryngology, University Hospital of Foggia, Foggia, Italy; 2 Department of Maxillofacial Surgery and
Otorhinolaryngology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 3 Directorate General, ASL BA, Bari,
Italy; 4 Department of Otorhinolaryngology, Hospital of Tolmezzo, ASUFC Udine, Udine, Italy; 5 Smell & Taste Clinic, Department of
Otorhinolaryngology, TU Dresden, Dresden, Germany


SUMMARY
Only a few studies have assessed smell and taste in Coronavirus Disease 2019 (COVID-19)
patients with psychophysical tests, while the majority performed self-rating evaluations.
Given the heterogeneity of the published literature, the aim of this review was to systemati-
cally analyse the articles on this topic with a focus on psychophysical testing. A search on
PubMed and Web of Science from December 2019, to November 2021, with cross-refer-
ences, was executed. The main eligibility criteria were English-language articles, investi-
gating the clinical features of olfaction and gustation in COVID-19 patients using self-rat-
ing assessment, psychophysical testing and imaging techniques. A total of 638 articles were
identified and 66 were included. Self-rating assessment was performed in 31 studies, while
psychophysical testing in 30 and imaging techniques in 5. The prevalence of chemosensory
dysfunction was the most investigated topic, followed by the recovery time. About the psy-
chophysical assessment, the extended version of the Sniffin’ Sticks was used in 11 articles
and the Connecticut Chemosensory Clinical Research Center test in another 11. The olfac-
tory threshold performance was the most impacted compared to the discrimination and
identification capacities in accordance with the hypothesis of a tropism of SARS-CoV-2 for
the olfactory mucosa. The timing significantly influenced the results of the psychophysical
testing with 20% of patients presenting olfactory dysfunction at one month after infection.
                                                                                                       Received: February 18, 2022
KEY WORDS: smell, olfaction disorders, taste, anosmia, rhinology, COVID-19, infections
                                                                                                       Accepted: February 22, 2022

RIASSUNTO                                                                                              Correspondence
La maggioranza degli studi ha valutato la capacità olfattiva e gustativa nei pazienti CO-              Eleonora M.C. Trecca
VID-19 con questionari e autovalutazione. Data l’eterogeneità della letteratura pubbli-                Department of Otolaryngology, University Hospital
cata, lo scopo di questa ‘review’ è stato quello di analizzare gli articoli sull’argomento,            of Foggia, viale Pinto 1, 71122 Foggia, Italy
focalizzando l’attenzione sui test psicofisici. È stata eseguita una ricerca su PubMed e Web           E-mail: eleonora.trecca@unifg.it
of Science da dicembre 2019 a novembre 2021. I principali criteri di inclusione sono stati
articoli in lingua inglese, che studiavano le caratteristiche cliniche dell’olfatto e del gusto          How to cite this article: Trecca EMC, Cassano
nei pazienti COVID-19 utilizzando test soggettivi, psicofisici e ‘imaging’ radiologico. In               M, Longo F, et al. Results from psychophysical
totale sono stati identificati 638 articoli e di questi ne sono stati inclusi 66. In 31 studi è          tests of smell and taste during the course of SARS-
stata eseguita una valutazione soggettiva, mentre in 30 sono stati utilizzati test psicofisici           CoV-2 infection: a review. Acta Otorhinolaryngol
e in 5 tecniche di ‘imaging’ radiologico. La prevalenza della disfunzione chemosensoriale                Ital 2022;42(SUPPL.1):S20-S35. https://doi.
è stata l’argomento più studiato, seguita dal tempo di recupero. Per quanto riguarda la                  org/10.14639/0392-100X-suppl.1-42-2022-03
valutazione psicofisica, gli Sniffin’ Sticks sono stati utilizzati in 11 articoli e il test del Con-
necticut Chemosensory Clinical Research Center in altri 11. La performance della soglia                © Società Italiana di Otorinolaringoiatria
                                                                                                       e Chirurgia Cervico-Facciale
olfattiva è stata la più intaccata rispetto alle capacità di discriminazione e identificazione
in linea con l’ipotesi di un tropismo del virus COVID-19 per la mucosa olfattoria. La tem-
                                                                                                                      OPEN ACCESS
pistica ha influenzato significativamente i risultati del test psicofisico con solo il 20% dei
pazienti affetti da disfunzione olfattiva dopo un mese dall’infezione.                                 This is an open access article distributed in accordance with
                                                                                                       the CC-BY-NC-ND (Creative Commons Attribution-Non-
PAROLE CHIAVE: olfatto, disturbi olfattivi, gusto, anosmia, COVID-19, infezioni                        Commercial-NoDerivatives 4.0 International) license. The
                                                                                                       article can be used by giving appropriate credit and mentio-
                                                                                                       ning the license, but only for non-commercial purposes and
                                                                                                       only in the original version. For further information: https://
                                                                                                       creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                              COVID-19 and chemosensory dysfunction




Introduction                                                     this systematic review, as well as records identified through
                                                                 websites and other organizations.
Chemosensory dysfunction due to upper respiratory tract
                                                                 The main eligibility criteria were English-language ar-
infection (URTI) can be caused by many common cold
                                                                 ticles, randomised and controlled trials in humans inves-
viruses, namely rhinovirus, adenovirus, influenza virus
                                                                 tigating the clinical features of olfaction and gustation in
and coronavirus, including Coronavirus Disease 2019
                                                                 COVID-19 patients using self-rating assessment, psycho-
(COVID-19), firstly detected in December 2019 in Cen-
                                                                 physical testing and/or imaging techniques. Articles us-
tral China, in the city of Wuhan 1. After China, Italy was
                                                                 ing psychophysical tests of any type (i.e., Sniffin’ Sticks
the first European country to experience a large-scale out-
                                                                 extended test, 16-item Sniffin’ Sticks identification test,
break in February 2020 with 4,757,231 confirmed cases
                                                                 Connecticut Chemosensory Clinical Research Center -
and 132,004 deaths as of October 2021 according to the
                                                                 CCCRC, University of Pennsylvania Smell Identification
World Health Organization (WHO). Since the beginning of
                                                                 Test - UPSIT) and quality, including validated screening
this pandemic, otolaryngologists have had a key role in the
                                                                 tests, were assessed for eligibility. Literature reviews, tech-
treatment of many symptoms of severe acute respiratory
                                                                 nical notes, letters to the editor, case reports, case series
syndrome coronavirus 2 (SARS-CoV-2) infection, such
as fever, cough, sore throat and smell and taste disorders,      or trials including less than 12 participants, instructional
which suddenly became known to everyone thanks to me-            courses and conference papers were excluded from this
dia attention and massive release of publications about this     systematic review. Papers not focusing on smell and taste
topic 2. However, quantity does not always imply quality,        in COVID-19 patients, and where the methodology was in-
and COVID-19 articles in the field of otolaryngology have        consistent, were also excluded.
been often related to poorer evidence levels than non-COV-
ID-19 and pre-COVID-19 articles 3,4. This is even truer in       Data extraction and quality assessment
the case of publications about smell and taste dysfunction       Two authors (E.M.C.T., M.C.) independently screened the
which were often based on subjective findings 5 and case         full-text version of each publication, conducted data extrac-
reports/small case series 6, with most of the studies using      tion and excluded those whose content was judged not to
self-administered tests or screening tests of olfactory func-    be relevant for the purpose of this review. When agreement
tion, especially in the first wave of pandemic because of        could not be reached, another author from the group (M.G.)
the cancellation of hospital visits and elective procedures 7.   was consulted, and another (F.L.) was asked for data ex-
Conversely, only a few studies have evaluated smell and          traction and quality assessment.
taste in COVID-19 patients with psychophysical tests 8,9.        Publications were classified according to the olfactory/gus-
Given the high heterogeneity of the published literature and     tatory assessment in self-rating evaluation, psychophysical
the increasing interest in olfaction and taste before, dur-      testing, and imaging techniques. Articles where psycho-
ing and after SARS-CoV-2 infection, the aim of this review       physical testing was used were further analysed according
was to systematically analyse the articles on this topic with    to the threshold, discrimination and identification olfactory
a focus on publications where smell and taste in COVID-19        performance.
patients has been assessed with psychophysical tests.            Among these three groups, topics of interest, such as recov-
                                                                 ery from chemosensory dysfunction, treatment outcomes
                                                                 and recovery time, were identified.
Materials and methods
                                                                 The general features of each article (i.e., journal, first author,
This systematic review was conceived according to the Pri-       country, year of publication, population, methods, preva-
mary Reporting Items for Systematic Reviews and Meta-            lence, topic of the paper, and study quality) were recorded
analyses (PRISMA) Guidelines 10,11.                              in a spreadsheet. The quality of the included studies was as-
                                                                 sessed using “The Strengthening the Reporting of Observa-
Search strategy and article selection process                    tional Studies in Epidemiology” (STROBE) Statement with
The National Library of Medicine through PubMed and              a score interval from 0 to 22, with a higher score indicating a
Web of Science were searched for the following keywords:         better study quality 12. To mitigate the risks of bias, papers of
“Smell” OR “Olfaction” OR “Taste” OR “Gustation”                 all quality were included in this systematic review.
OR “Olfaction disorders” OR “Anosmia” OR “Rhinol-
ogy” AND “COVID-19” OR “SARS-CoV-2 infection”.
The first author collected articles published between De-
                                                                 Results
cember 2019, and November 2021. Also, references of the          Seventy-eight articles were identified through other meth-
collected articles were considered potentially eligible for      ods (i.e., websites, organisations, citation searching), and



                                                                                                                              S21
E.M.C. Trecca et al.




Figure 1. PRISMA (Primary Reporting Items for Systematic Reviews and Meta-analyses) flow diagram.


1018 via databases (i.e., PubMed, Web of Science). After                     evaluation of the ethyl alcohol olfactory threshold and
excluding duplicates, 638 articles were considered poten-                    discriminative function for six common household odorants
tially eligible for screening. Out of these, 72 publications                 in one 56.
were not retrieved and 500 were eliminated for the fol-                      Concerning gustatory assessment, taste strips were used in
lowing reasons (Fig. 1): written in languages other than                     3 articles 46,49,51 and taste sprays in 3 9,56,57.
English (n = 41); other than original articles (i.e., reviews,               Results from psychophysical tests of smell during SARS-
editorials, case reports etc.: n = 280); not being directly                  CoV-2 infection (Tab. IV) showed that the olfactory
relevant to the topic (n = 68) and methodology inconsistent                  threshold score was more impacted than the odour
(n = 111). After these exclusions, 66 papers were included                   discrimination and identification scores in the studies
for final analysis.                                                          using the extended version of the Sniffin’ Sticks test. In
Regarding the olfactory/gustatory testing used, self-rating                  fact, this group of articles presented an overall threshold,
assessment was used in 31 studies 13-42 (Tab. I), and psycho-                discrimination and identification (TDI) score of 22.5 ± 7.8
physical testing in 30 9,43-70 (Tab. II). Lastly, imaging tech-              indicating moderate hyposmia, while the threshold score
niques were used in 5 articles 71-75 (Tab. III).                             was 5.2 ± 1.3 and the discrimination and identification,
About the olfactory assessment, the extended version of the                  respectively, were 10.8 ± 0.9 and 10.7 ± 1.0. Similarly, the
Sniffin’ Sticks test was used in 11 articles 9,44,46,48,50,51,67,68,72-74,   CCCRC and the UPSIT global scores were, respectively,
Connecticut Chemosensory Clinical Research Center (CC-                       40.8 ± 14.7 and 25.2 ± 2.5, indicating moderate hyposmia.
CRC) olfactory test in 11 43,57,61-67,69,70, the 16-item Sniffin’            With screening tests, scores from the 12-item BSIT were
Sticks identification test in 7 31,32,49,52-54,60, University of             8.5 ± 0.5 (hyposmia: ≤ 9) 76 and 11.6 ± 0.8 from the 16-item
Pennsylvania Smell Identification Test (UPSIT) in 3 45,47,55,                Sniffin’ Sticks identification (normosmia: ≥ 12) 77.
a new validated psychophysical self-administered test in                     The prevalence of chemosensory dysfunction was the most
3 57,69,70, 12-item Brief Smell Identification Test (BSIT) in                investigated topic in half of articles (n = 33), followed
2 58,59, an olfactory and gustatory home test in one 28 and                  by recovery time in 8 articles (Fig. 2). Other topics of



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                                                                                                                    COVID-19 and chemosensory dysfunction




Table I. Features of the studies using self-rating assessment.
 Source                Year      Country             Study            Methods               Prevalence           Recovery           Topic            STROBE
                                                  population                                                       time                               score*
 1    Altundag A 13     2021   Turkey, USA     135 COVID-19           Structured         OD: 59.3%; Mean           N/A         Prevalence and          20
                                                  patients           questionnaire       recovery: 7.8 days                      recovery of
                                                                                                                               chemosensory
                                                                                                                                 dysfunction
 2    Bagheri SH 14     2020       Iran       10 069 COVID-19         Structured        OD: anosmia 60.9%,         N/A          Prevalence of          20
                                                  patients           questionnaire       80.4% combined                        chemosensory
                                                                                            dysfunction                          dysfunction
 3    Barillari MR 15   2020       Italy       294 COVID-19           Validated           OD: 70.4%; GD:           N/A          Prevalence of          21
                                                  patients          questionnaires            59.2%                            chemosensory
                                                                                                                                 dysfunction
 4    Boscolo Rizzo     2021   Multicentric    268 COVID-19           Validated              Combined              N/A          Prevalence of          22
      P 16                                        patients          questionnaires         chemosensory                        chemosensory
                                                                                        dysfunction: 81.3%;                      dysfunction
                                                                                          OD: 10.2%; GD
                                                                                               8.6%
 5    Boscolo-Rizzo     2020     Italy, UK     187 COVID-19           Validated            Baseline: - OD          N/A          Prevalence of          21
      P 18                                        patients          questionnaires        or GD: 60.4%; 4                       chemosensory
                                                                                         weeks: - complete                     dysfunction and
                                                                                            resolution or                       recovery time
                                                                                        improvement: 89%
 6    Boscolo-Rizzo     2020       Italy        296 household         Structured          OD or GD: 25%            N/A          Prevalence of          21
      P 17                                    contacts of home-      questionnaire                                              chemosensory
                                              isolated COVID-19                                                                  dysfunction
                                                    patients
 7    Chapurin N 19     2021       USA          1003 COVID-19         Validated          OD and GD: 73%          19.7 days       Prevalence of         20
                                                    patients        questionnaires                                               chemosensory
                                                                                                                                   dysfunction
 8    Chiesa-           2020   Multicentric    751 COVID-19           Validated         OD: 82.7%; anosmia         N/A          Prevalence and         22
      Estomba                                     patients          questionnaires      83%, hyposmia 17%                          recovery of
      CM 20                                                                                                                      chemosensory
                                                                                                                                   dysfunction
 9    Cho RHW 21        2020   Hong Kong        83 COVID-19           Structured           OD: 47%; GD:          OD: 10.3    Correlation between       22
                                                 patients; 60        questionnaire            43.4%              days; GD:   olfactory dysfunction
                                                   controls                                                      9.5 days         and viral load

 10 Gerkin RC 22        2021   Multicentric    4148 COVID-19           Validated                 N/A               N/A         Predictive value        22
                                                  patients        questionnaires; VAS                                         of olfactory loss in
                                                                                                                                   COVID-19
 11 Gorzkowski          2020     France        229 COVID-19           Structured             OD: 70.3%           11.6 days       Prevalence of         22
    V 23                                          patients           questionnaire                                              chemosensory
                                                                                                                               dysfunction and
                                                                                                                                 recovery time
 12 Haehner A 24        2020    Germany         500 patients         Structured          Smell and/or taste        N/A         Predictive value        19
                                               suspected for      questionnaire; VAS       loss: 13.8%                        of olfactory loss in
                                               COVID-19: 34          for OD/GD                                                     COVID-19
                                              confirmed cases
 13 Hopkins C 25        2021   Multicentric   434 responders;         Structured          6 months: 40.9%          N/A           Prevalence of         20
                                               114 COVID-19          questionnaire      patients normosmic;                     chemosensory
                                                  patients                              97.2% normogeusic                         dysfunction
 14 Iravani B 26        2020   Multicentric    2440 patients        Data collection         Relationship           N/A         Predictive value        21
                                                                       website              between the                       of olfactory loss in
                                                                   smelltracker.org     COVID-19 prediction                        COVID-19
                                                                                          model and odour
                                                                                        intensity ratings over
                                                                                          time, ρ = -0.83,
                                                                                             P < 0.001
                                                                                                                                                            u




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E.M.C. Trecca et al.




Table I. Features of the studies using self-rating assessment (follows).
 Source                Year      Country             Study               Methods            Prevalence         Recovery           Topic          STROBE
                                                  population                                                     time                             score*
 15 Jalessi M 27       2021      Iran, UK      243 COVID-19           Validated          OD: 88.5% anosmia        N/A         Prevalence of        20
                                                  patients          questionnaires          at the onset.                     chemosensory
                                                                                                                               dysfunction
 16 Konstantinidis     2020      Greece        79 COVID-19        VAS; olfactory and      OD: 36.7%; GD:          N/A         Prevalence of        22
    I 28                                         patients        gustatory home test          27.8%                           chemosensory
                                                                                                                               dysfunction
 17 Lal P 83           2021       India        435 COVID-19          Structured            OD and/or GD:       - OD 12.1      Recovery time        15
                                                  patients          questionnaire             10.8%            days; - GD
                                                                                                               10.8 days
 18 Lechien JR 29      2020    Multicentric    417 COVID-19           Validated           OD: 85.6%. GD:          N/A          Prevalence of       21
                                                  patients          questionnaires            88.0%                           chemosensory
                                                                                                                                dysfunction
 19 Lechien JR 32      2021    Multicentric   2581 COVID-19            Validated           OD: 85.9% (mild     - OD 21.6      Prevalence and       20
                                                 patients           questionnaires;       forms) moderate-        days          recovery of
                                                                     Sniffin’ sticks       to-critical forms                  chemosensory
                                                                   identification test        (4.5-6.9%).                       dysfunction
                                                                     (233 patients)         Psychophysical
                                                                                            testing: 54.7%
                                                                                         hyposmia/anosmia
 20 Lechien JR 31      2021    Multicentric   2579 COVID-19            Validated              OD: 73.7%.          N/A         Prevalence of        20
                                                 patients           questionnaires;           GD: 46.8%.                      chemosensory
                                                                     Sniffin’ sticks        Psychophysical                     dysfunction
                                                                   identification test      testing: 23.5%
                                                                     (231 patients)        anosmia; 18.6%
                                                                                               hyposmia
 21 Lechien JR 30      2020    Multicentric   1420 COVID-19           Validated            OD: 70.2%; GD:         N/A          Prevalence of       20
                                European         patients           questionnaires               54.2%                         chemosensory
                                                                                                                                dysfunction
 22 Locatello LG 33 2021           Italy       101 COVID-19           Validated            Chemosensory           N/A       Treatment outcomes     21
                                                  patients          questionnaires       dysfunction; - One
                                                                                         month: 44%; -Three
                                                                                           months: 37%
 23 Lucidi D 34        2020        Italy       110 COVID-19           Validated                  N/A           Complete       Prevalence of        20
                                                  patients          questionnaires                             recovery:      chemosensory
                                                                                                               7-14 days       dysfunction
                                                                                                                 in 63%
                                                                                                                patients.
                                                                                                                  Partial
                                                                                                               recovery:
                                                                                                                   1-3
                                                                                                                months
                                                                                                                 in 22%
                                                                                                                patients
 24 Maiorano E 35      2021        Italy       170 COVID-19          Structured           OD and GD: 96%           N/A        Prevalence of        19
                                                  patients        questionnaire; VAS                                          chemosensory
                                                                     for OD/GD                                                 dysfunction
 25 Paderno A 36       2020        Italy       508 COVID-19          Structured          OD: 56%; GD: 63%         N/A         Prevalence of        22
                                                  patients          questionnaire                                             chemosensory
                                                                                                                               dysfunction
 26 Parma V 37         2020    Multicentric   4039 COVID-19           Validated         Mean reduction            N/A         Prevalence of        22
                                                 patients           questionnaires    of smell: -79.7%;                       chemosensory
                                                                                        taste: -69.0%;                         dysfunction
                                                                                     chemestetic: -37.3%
 27 Qiu C 38           2020    Multicentric    394 COVID-19           Validated         Olfactory and/            N/A         Prevalence of        22
                                                  patients       questionnaires, VAS      or gustatory                        chemosensory
                                                                                       dysfunction: 41%                        dysfunction
                                                                                                                                                        u




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Table I. Features of the studies using self-rating assessment (follows).
 Source                Year      Country             Study               Methods                           Prevalence        Recovery          Topic            STROBE
                                                  population                                                                   time                              score*
 28 Raad N 39             2021           Iran         1299 COVID-19              Validated              Parosmia: 10.8%        N/A         Prevalence of          20
                                                          patients             questionnaires                                                parosmia
 29 Spinato G 40          2021           Italy         230 COVID-19              Validated                     N/A             N/A         Validation of a        21
                                                        patients; 230          questionnaires                                              questionnaire
                                                          controls
 30 Vaira LA 41           2021      Multicentric       153 COVID-19              Validated              OD: 62.3%. GD:         N/A          Prevalence of         21
                                                        patients after         questionnaires               53.6%                          chemosensory
                                                         vaccination                                                                       dysfunction in
                                                                                                                                          COVID-19 cases
                                                                                                                                          after vaccination
 31 Yan CH 42             2020          USA            128 COVID-19              Structured             OD: -hospitalized      N/A        Predictive value        19
                                                          patients              questionnaire          26.9%, outpatients                of olfactory loss in
                                                                                                          66.7%; GD:                          COVID-19
                                                                                                      -hospitalized 23.1%,
                                                                                                       outpatients 62.7%
OD: indicates olfactory dysfunction; GD: gustatory dysfunction; N/A: not applicable; VAS: visual analogue scale.
*
  Scores interval from 0 to 22, with higher scores showing better study quality 12.



Table II. Features of the studies using psychophysical testing.
 Source                Year      Country           Study                          Methods                  Prevalence        Recovery          Topic            STROBE
                                                population                                                                     time                              score*
 1     Amadu AM 43        2021      Multicentric        46 COVID-19                CCCRC              OD: 76.1%; anosmia       N/A           Correlation          21
                                                          patients                                       26.1%, severe                   between olfactory
                                                                                                       hyposmia 21.7%,                  dysfunction and lung
                                                                                                      moderate hyposmia                     involvement
                                                                                                            28.3%
 2     Bordin A 44        2021           Italy         101 COVID-19            Sniffin’ sticks;         6 months: - OD:        N/A         Prevalence of          21
                                                          patients               validated                  55.6%                          chemosensory
                                                                               questionnaires                                             dysfunction and
                                                                                                                                           recovery time
 3     Boscolo Rizzo      2021      Multicentric       145 COVID-19                 UPSIT          6 months: -OD 60%,          N/A         Recovery time          21
       P 45                                               patients                                     anosmia 6.9%,
                                                                                                      severe hyposmia
                                                                                                            4.8%
 4     Boscolo-Rizzo      2021      Multicentric       100 COVID-19         Sniffin’ sticks, taste    Orthonasal smell         N/A         Prevalence of          22
       P 46                                               patients           strips, screening          in COVID-19                        chemosensory
                                                                               for intranasal        patients: OD 46%                       dysfunction
                                                                                  trigeminal           (7% anosmic).
                                                                            dysfunction (visual Gustatory function in
                                                                             analogue scale)        COVID-19 patients:
                                                                                                       GD 27%. Nasal
                                                                                                   trigeminal sensitivity
                                                                                                   significantly lower in
                                                                                                    COVID-19 patients
 5     González C 47      2021       Chile, USA        100 COVID-19                  UPSIT         OD: -Baseline 75%;          N/A         Prevalence of          21
                                                        patients; 63                                 -One month: 41%                       chemosensory
                                                          controls                                                                          dysfunction
 6     Iannuzzi L 48      2020           Italy         30 COVID-19              Sniffin’ sticks;         10% anosmia,        1 month       Recovery time          21
                                                          patients                 validated            > 50% hyposmia
                                                                                questionnaires
                                                                               (VAS, Hyposmia
                                                                                 rating scale)



                                                                                                                                                                       u




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E.M.C. Trecca et al.




Table II. Features of the studies using psychophysical testing (follows).
 Source                Year      Country           Study                 Methods             Prevalence         Recovery         Topic          STROBE
                                                population                                                        time                           score*
 7     Le Bon SD 51    2021    Multicentric    72 COVID-19       Sniffin’ sticks, taste   OD: anosmia 8%,         N/A        Prevalence of        22
                                                 patients           strips, screening      hyposmia 29%,                     chemosensory
                                                                      for intranasal       normosmia 63%                      dysfunction
                                                                         trigeminal
                                                                        dysfunction
                                                                    (identification of
                                                                          menthol)
 8     Le Bon SD 49    2021    Multicentric    93 COVID-19             Sniffin’sticks   OD: 18% hyposmic,         N/A        Prevalence of        20
                                                 patients        (identification test);   3% anosmic. GD:                    chemosensory
                                                                        taste strips    12% hypogeusic, no                    dysfunction
                                                                                           ageusic patients
 9     Le Bon SD 50    2021      Belgium       27 COVID-19            Sniffin’ sticks      Improvement in         N/A      Treatment outcomes     21
                                                 patients                                   the group oral
                                                                                          corticosteroids +
                                                                                          olfactory training:
                                                                                        7.7 points; olfactory
                                                                                         training: 2.1 points
 10    Lechien JR 54   2020    Multicentric    78 COVID-19                Validated      OD: 11% anosmia;         N/A        Prevalence of        20
                                                 patients            questionnaires;        24% hyposmia                     chemosensory
                                                                      Sniffin’ sticks                                         dysfunction
                                                                   identification test
                                                                       (46 patients)
 11    Lechien JR 53   2020    Multicentric    88 COVID-19            Sniffin’ sticks        OD: 44.6%.           N/A        Recovery time        20
                                                 patients             (identification       Recovery at 2
                                                                     test); validated      months: 79.5%
                                                                     questionnaires
 12    Lechien JR 52   2020    Multicentric    47 COVID-19             Sniffin’sticks    OD: 8.5% anosmia,        N/A        Prevalence of        19
                                                 patients             (identification     19.1% hyposmia                     chemosensory
                                                                     test); validated                                         dysfunction
                                                                     questionnaires
 13    Moein ST 55     2020        Iran        100 COVID-19                 UPSIT       OD: -Baseline: 96%;       N/A         Prevalence of       22
                                                  patients                              -after 5 weeks: 63%                   chemosensory
                                                                                                                             dysfunction and
                                                                                                                              recovery time
 14 Niklassen AS 9 2021        Multicentric    111 COVID-19      Sniffin’ sticks, taste   OD: 21% anosmia;      28 days       Prevalence of       22
                                                  patients              sprays            49% hyposmia; GD:                   chemosensory
                                                                                                26%                          dysfunction and
                                                                                                                              recovery time
 15 Petrocelli M 56 2021       Multicentric    300 COVID-19         Evaluation of the  Baseline: anosmia          N/A         Recovery time       19
                                                  patients             ethyl alcohol  47%, ageusia 38%;
                                                                         olfactory     6 months: anosmia
                                                                   threshold and the    5%, ageusia 1%
                                                                      discriminative
                                                                     function for six
                                                                  groups of common
                                                                 household odorants.
                                                                       Taste sprays
 16 Petrocelli M 94 2020           Italy       300 COVID-19              Validated       OD and/or GD:            N/A        Prevalence of        19
                                                  patients       psychophysical self- 70%; anosmia 47%,                      chemosensory
                                                                   administered test     ageusia 38%                          dysfunction
 17 Prajapati DP 58 2020           USA         81 COVID-19               12-item          OD: 66.6%               N/A        Prevalence of        21
                                                 patients               BSIT; VAS                                            chemosensory
                                                                                                                              dysfunction




                                                                                                                                                       u




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                                                                                                                    COVID-19 and chemosensory dysfunction




Table II. Features of the studies using psychophysical testing (follows).
 Source                Year      Country           Study                 Methods             Prevalence          Recovery          Topic            STROBE
                                                population                                                         time                              score*
 18 Prajapati DP 59 2021           USA         52 COVID-19              12-item               OD: 63%            12 days       Prevalence of          21
                                                 patients              BSIT; VAS                                               chemosensory
                                                                                                                              dysfunction and
                                                                                                                               recovery time
 19    Saussez S 60    2021    Multicentric    288 COVID-19            Validated           Baseline: anosmia       N/A         Recovery time          20
                                                  patients          questionnaires;        39.2%, hyposmia
                                                                     Sniffin’ sticks        13.2%; 60 days:
                                                                   identification test       anosmia 9.4%,
                                                                                             hyposmia 16%
 20     Vaira LA 68    2021    Multicentric    170 COVID-19          Sniffin’ sticks      COVID-19 patients:       N/A         Prevalence of          22
                                                patients; 170                              anosmia in 4.7%,                    chemosensory
                                                  controls                                hyposmia in 21.8%                     dysfunction
                                                                                            cases. Controls:
                                                                                           hyposmia in 3.5%
                                                                                                 cases
 21     Vaira LA 63    2021    Multicentric    60 COVID-19              CCCRC             Prevalence of OD =       N/A      Correlation between       22
                                                 patients                                   76.7%; anosmia                  olfactory dysfunction
                                                                                              20%, severe                       and viral load
                                                                                           hyposmia 18.3%,
                                                                                         moderate hyposmia
                                                                                              18.3%, mild
                                                                                           hyposmia 16.7%
 22     Vaira LA 62    2021    Multicentric    77 COVID-19              CCCRC             Prevalence of OD=        N/A      Correlation between       21
                                                 patients                                    74%; anosmia                   olfactory dysfunction
                                                                                             18.1%, severe                    and inflammatory
                                                                                           hyposmia 16.9%,                         markers
                                                                                         moderate hyposmia
                                                                                              24.7%, mild
                                                                                           hyposmia 14.3%
 23     Vaira LA 61    2021    Multicentric    74 COVID-19              CCCRC             OD: mild hyposmia        N/A      Correlation between       21
                                                 patients                                  14.9%, moderate                  olfactory dysfunction
                                                                                           hyposmia 24.3%,                    and inflammatory
                                                                                            severe hyposmia                        markers
                                                                                             16.2, anosmia
                                                                                                 18.9%
 24     Vaira LA 67    2021    Multicentric    774 COVID-19       Sniffin-Sticks test,        OD = 62.1%:          N/A         Prevalence of          21
                                                  patients              CCCRC              hyposmic 36.2%,                     chemosensory
                                                                                            anosmic 25.9%                       dysfunction
 25     Vaira LA 66    2021    Multicentric    18 COVID-19              CCCRC               Median olfactory       N/A      Treatment outcomes        22
                                                 patients                                   score: -Baseline:
                                                                                         treatment group 10;
                                                                                               controls 20
 26     Vaira LA 65    2020    Multicentric    138 COVID-19             CCCRC                Chemosensory          N/A         Recovery time          19
                                                  patients                               dysfunction: baseline
                                                                                           84.8%; 2 months
                                                                                                  7.2%
 27     Vaira LA 64    2020    Multicentric    106 COVID-19             CCCRC             Baseline: OD 67%,        N/A       Prognostic value of      19
                                                  patients                                     GD 65.6%                     olfactory dysfunction
 28     Vaira LA 69    2020        Italy       345 COVID-19            Validated           OD: mild disease        N/A          Prevalence of         20
                                                  patients         psychophysical          66.6%; moderate                      chemosensory
                                                                  self-administered      67%; severe 69.2%                       dysfunction
                                                                    test; CCCRC             GD: mild 70.2%,
                                                                                           moderate 71.3%,
                                                                                             severe 65.4%.



                                                                                                                                                           u




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E.M.C. Trecca et al.




Table II. Features of the studies using psychophysical testing (follows).
 Source                Year      Country           Study                 Methods                       Prevalence           Recovery             Topic             STROBE
                                                population                                                                    time                                  score*
 29      Vaira LA 70      2020         Italy          33 COVID-19               Validated                   N/A                 N/A         Validation of a           21
                                                        patients            psychophysical                                                 self-administered
                                                                           self-administered                                                 olfactory and
                                                                             test; CCCRC                                                     gustatory test
 30      Vaira LA 57      2020         Italy          72 COVID-19            CCCRC, taste          OD: anosmia 2.8%,            N/A          Prevalence of            22
                                                        patients                 sprays             hyposmia 80.6%.                         chemosensory
                                                                                                   GD: ageusia 1.4%,                          dysfunction
                                                                                                   hypogeusia 47.2%
Abbreviations: CCCRC: indicates Connecticut Chemosensory Clinical Research Center test; OD: olfactory dysfunction; GD: gustatory dysfunction; UPSIT: University of Pennsylvania
Smell Identification test; VAS: Visual Analogue Scale; BSIT: Brief Smell Identification Test.
*Scores interval from 0 to 22, with higher scores showing better study quality 12.



Table III. Features of the studies using imaging techniques.
 Source                 Year     Country            Study                      Methods                 Prevalence           Recovery             Topic             STROBE
                                                 population                                                                   time                                  score*
  1     Altundag A 71     2020     Turkey, USA       91 cases: 24            CT scan, MRI          COVID-19 patients:           N/A       Radiological study          22
                                                    cases COVID-19                                  100% anosmic
                                                      patients, 38
                                                      patients with
                                                      PIOD, and a
                                                    control group of
                                                       29 patients
  2     Kandemirli        2021     Turkey, USA       23 COVID-19    Sniffin’ sticks, CT            COVID-19 patients:           N/A       Radiological study          20
          SG 72                                         patients        scan, MRI                   100% anosmic
  3    Lechien JR 73      2020     Multicentric      16 COVID-19         Validated                 COVID-19 patients:           N/A       Radiological study          22
                                                        patients      questionnaire,                100% anosmic
                                                                      Sniffin’ sticks,
                                                                      olfactory cleft
                                                                    examination, CT
                                                                           scan
  4     Tekcan Sanli      2021     Turkey, USA    50 COVID-19       Sniffin’ sticks, CT                     N/A                 N/A       Radiological study          21
            DE 74                                    patients              scan.
  5     Yildirim D 75     2021     Turkey, USA    31 COVID-19      Olfactory bulb MRI,             COVID-19 patients:           N/A       Radiological study          21
                                                   patients, 97    DTI, and olfactory                100% anosmic;
                                                patients with PIOD         fMRI                       PIOD patients:
                                                                                                    18.6% hyposmic,
                                                                                                     81.4% anosmic
PIOD: indicates post-infectious olfactory disorder; CT: computed tomography; MRI: magnetic resonance imaging; N/A: not applicable.
*Scores interval from 0 to 22, with higher scores showing better study quality 12.



interest were studies using imaging techniques (n = 5), the                                Discussion
predictive value of olfactory loss in COVID-19 (n = 5),
miscellaneous (n = 5) and studies investigating both the                                   The results of this review demonstrate that the prevalence of
prevalence of chemosensory dysfunction and recovery time                                   olfactory and gustatory dysfunction in COVID-19 patients
(n = 5). Less explored themes were treatment outcomes                                      is highly variable in the current literature and depends on
(n = 3) and validation of new tests (n = 2).                                               the methodology used. In fact, the prevalence of olfactory
About the recovery time (Fig. 3), results from psychophysical                              dysfunction ranges from 14 to 89% in case of assessments
tests (i.e., Sniffin’ Sticks extended test, CCCRC) showed a                                based on self-ratings (Tab. I), while it ranges from 21 to 96%
prevalence of olfactory dysfunction about the 70% during                                   in case of psychophysical assessment (Tab. II). Regarding
SARS-CoV-2 infection, with only 20% of patients still                                      taste impairment, although generally less present 78, we
presenting impairment after one month.                                                     found rates of 9 to 88% based on self-ratings (Tab. I) and of
Within the included articles, 32 (48.5%) were multicentric.                                12 to 66% based on psychophysical testing. This discrepancy



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                                                                                                                  COVID-19 and chemosensory dysfunction




Figure 2. Topics of included articles about COVID-19 chemosensory dysfunction from December 2019 to November 2021. Prevalence of chemosensory dys-
function was the most investigated topic.




Figure 3. Recovery time of olfactory dysfunction evaluated using psychophysical testing. The figure shows the prevalence of patients suffering from olfactory
dysfunction according to the timing of SARS-CoV-2 infection.



is partly due to the fact that the importance attributed to                      Other studies used only the responses to taste or smell-related
smell, taste and flavour varies among the general population                     questions of certain patient response outcome measures,
according to sex, age and sociocultural factors, which is a                      like the Sinonasal Outcome test 22 (SNOT-22) 16,19. Only
major bias in response behaviour 79-82. In fact, many studies                    a few studies used validated questionnaires specifically
adopted visual analogue scales (VAS) to rate olfactory/                          investigating smell impairment such as the Questionnaire of
gustatory dysfunction 28,35, as well as ad hoc questions 83.                     Olfactory Dysfunction (QOD) 38 or the short version of the



                                                                                                                                                       S29
E.M.C. Trecca et al.




Questionnaire of Olfactory Disorders-Negative Statements                                      cognitive processing of olfactory information. The SARS-
(sQOD-NS) 29. However, the prevalence of olfactory/                                           CoV-2 virus has a major tropism for the nasal structures,
gustatory dysfunction varies remarkably among the studies                                     such as the olfactory epithelium, which may partly
(Tabs. II, IV) where psychophysical assessment was                                            explain the stronger effect on odour thresholds than odour
conducted with a wide range of tests that highly differ from                                  identification. For further analysis of global olfactory
each other (i.e., Sniffin’ Sticks extended version, CCCRC                                     function, a comprehensive evaluation using the extended
olfactory test, UPSIT, BSIT, home self-administered test,                                     version of the Sniffin’ Sticks test is preferable to an odour
taste sprays, taste strips). Many research groups used only                                   identification test alone, whenever possible.
screening tests to assess olfactory function, such as the                                     The recovery time was the second most investigated
12-item BSIT 58,59 or the 16-item smell identification test of                                parameter with eight articles focusing on this
the Sniffin’ Sticks battery 53,60. However, the Sniffin’ Sticks                               topic 9,45,48,53,56,60,65,83 and another five studying both the
test in its full version consists of three subtests aiming at                                 prevalence of chemosensory dysfunction and recovery
thorough evaluation of the olfactory capacity of individuals.                                 time 18,23,44,55,59. The recovery time was on average 14.3 days
The test results in a comprehensive TDI score 1-48 with                                       for olfactory function and 10.2 days for gustatory function
scores > 30.5 indicating normosmia 84. Conversely, other                                      according to the studies included in Table I in which self-
olfactory tests are less difficult, less expensive and less                                   ratings of smell function were performed. Similarly, it was
time-consuming, but they do not provide such an extensive                                     23.3 days for olfaction according to the articles included
assessment as the Sniffin’ sticks. In fact, the UPSIT 85 is a                                 in Table II in which psychophysical testing was executed.
smell identification test and the CCCRC 86 includes only the                                  Studies investigating the long-term outcomes of olfactory
smell detection threshold (using the method of ascending                                      dysfunction showed chemosensory dysfunction in 7% of
limits) and smell identification assessment. Similarly, for                                   patients at 2 months 65 with the 80% of COVID-19 patients
gustatory assessment, the taste sprays used in many of the                                    reporting olfactory recovery 53. Using the UPSIT another
studies included can be considered just as a screening test.                                  article suggested severe microsmia in 2% and anosmia
Conversely, the taste strips allow to collect more accurate                                   in 5% of COVID-19 patients after 6-month follow-up 45.
data about the primary taste which is impacted (i.e., sweet,                                  Hence, the timing of the evaluation during and after SARS-
salty, bitter, and sour) and to classify taste capacity of                                    CoV-2 infection significantly influences the results of the
patients in normogeusia and hypogeusia 87.                                                    psychophysical tests. This is important as patients who
Interestingly, results from psychophysical tests of                                           show persistent dysfunction after 15-20 days should be
olfactory function presented in Table IV showed that the                                      referred to an otolaryngologist to be tested and to start timely
threshold score was significantly more impacted than                                          treatment that includes safety counselling (e.g., maintain
the discrimination and identification performances in the                                     smoke and gas detectors, monitor spoiled food), olfactory
studies using the extended version of the Sniffin’ Sticks                                     training and possible adjuvant medication (e.g., intranasal
test (T: 5.2 ± 1.3; D: 10.8 ± 0.9; I: 10.7 ± 1.0). This also                                  vitamin A, systemic omega 3) 88. Regarding treatment,
appears to be valid in publications using the CCCRC (T:                                       a pilot study in a small sample of patients included in
18.8 versus I: 47.6), although this test does not evaluate the                                Table II of this review using the Sniffin’ sticks test reported
discrimination capacity as the Sniffin’ Sticks. Therefore,                                    that a 10-day treatment of oral corticosteroids associated
the results of psychophysical tests suggest that COVID-19                                     with olfactory training led to significant improvement of
olfactory dysfunction impacts less the more complex                                           the olfactory score compared to olfactory training alone 50.


Table IV. Results from psychophysical tests of smell during SARS-CoV-2 infection. Results are presented as mean plus standard deviation.
 Test                                       Threshold            Discrimination              Identification           TDI score          CCCRC score
 Sniffin’ sticks extended test                      5.2 ± 1.3                   10.8 ± 0.9                    10.7 ± 1.0                  22.5 ± 7.8                   N/A
 CCCRC                                                18.8*                        N/A                          47.6*                        N/A                   40.8 ± 14.7
 UPSIT                                                 N/A                         N/A                        25.2 ± 2.5                     N/A                       N/A
 16-item Sniffin’ stick identification                 N/A                         N/A                        11.6 ± 0.8                     N/A                       N/A
 test
 12-item brief BSIT                                     N/A                         N/A                        8.5 ± 0.5                      N/A                       N/A
BSIT: indicates Brief Smell Identification Test; N/A: not applicable; CCCRC: Connecticut Chemosensory Clinical Research Center test; UPSIT: The University of Pennsylvania Smell
Identification test; TDI score: threshold discrimination identification score.
* Results of CCCRC score according to threshold and identification scores were presented only in the article “Objective evaluation of anosmia and ageusia in COVID-19 patients: Single-
center experience on 72 cases”. By Vaira LA et al. 57.




S30
                                                                                               COVID-19 and chemosensory dysfunction




However, there is skepticism in the current literature about      four publications studied the correlation between olfactory
the use of systemic corticosteroids to treat COVID-19             dysfunction and inflammatory markers 61,62 as well as lung
olfactory impairment as documented in an international            involvement 43 and viral load 21. For inflammatory markers,
consensus article 89. In fact, the experts have called for        the level of interleukin 6 (IL-6), which is known to be a
caution against the use of oral corticosteroids because of        proinflammatory cytokine secreted by COVID-19 infected
the lack of solid scientific evidence and the potential side      cells, was found to be significantly correlated with the se-
effects (i.e., glaucoma, hip fractures). Moreover, COVID-         verity of SARS-CoV-2 infection with a directly propor-
19-related olfactory impairment tends to spontaneously            tional association, but the correlation between IL-6 plasma
recover in one month. Additionally, conventional intranasal       concentrations and olfactory performance was not signifi-
administration of topical steroids does not appear to be          cant 61. Additionally, smell dysfunction seems to have poor-
an effective therapeutic option since steroid sprays do not       er prognostic value in predicting the severity of COVID-19
appropriately reach the olfactory cleft 90.                       compared to other systemic inflammatory markers (i.e., D-
The debate concerning the pathogenesis of SARS-CoV-2              dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte
chemosensory dysfunction is still open and some studies           ratio). These findings could suggest that the pathogenesis
have postulated that the viral-associated damage might be         of COVID-19 chemosensory dysfunction is more likely
extended not only to the olfactory epithelium, but also to        due to intranasal local factors rather than to systemic in-
the olfactory bulb and the central nervous system 8. Five         flammation 62. Lung involvement detected by CT in COV-
studies 71-75 included in Table III used imaging techniques       ID-19 patients did not exhibit a significant correlation with
(i.e., computed tomography-CT scan, magnetic resonance            olfactory performance measured by CCCRC 43.
imaging-MRI) to investigate chemosensory dysfunction in           Finally, new tools were developed and validated to overcome
COVID-19 patients and contributed to the understanding            many limitations that arose during various lockdown meas-
of the mechanisms underlying smell and taste impairment.          ures and hospital reorganisation due to the COVID-19 pan-
In these radiological studies, abnormalities such as higher       demic 7. It is worth mentioning the COVID-19 Questionnaire
olfactory cleft width and volume 71,74 and decreased white        (COVID-Q) 40, a novel symptom questionnaire specific for
matter tract integrity of olfactory regions were detected in      COVID-19 to identify patients who are likely to suffer from
COVID-19 patients 75. In contrast, a post-mortem study on         SARS-CoV-2 infection, and the validation of a self-adminis-
85 COVID-19 deceased patients demonstrated that susten-           tered olfactory and gustatory test for the remote evaluation of
tacular cells are the main target in the olfactory mucosa,        COVID-19 patients 70. Precisely, the COVID-Q 40 was tested
while olfactory sensory neurons and parenchyma of the ol-         on 230 non-hospitalised COVID-19 patients and 230 controls
factory bulb are not affected 91. Another recent review of        enrolled at Treviso Hospital. The questionnaire included 27
animal and human studies also suggested that infections of        items in its final version, which relate to “asthenia”, “gastro-
the olfactory epithelium in COVID-19 patients rarely re-          intestinal symptoms”, “ear and nose symptoms”, “breathing
sult in a brain infection because of the lack of entry pro-       issues”, “throat symptoms”, “anosmia/ageusia” and “muscle
tein expression in olfactory neurons that creates a barrier 92.   pain”. Interestingly, “anosmia/ageusia” items were signifi-
Therefore, the neurotrophic action of COVID-19 is still           cantly correlated with rates of positive COVID-19 test positiv-
uncertain, and this is in accordance with the results of the      ity. Concerning the self-administered olfactory and gustatory
psychophysical tests of this review showing that olfactory        tests for remote evaluation of COVID-19 patients 70, these
threshold performance is more impacted than discrimina-           have been assessed in 33 home-quarantined COVID-19 pa-
tion and identification capacities (Tab. IV).                     tients and the results compared with those obtained from the
Olfactory dysfunction is now globally recognised as a key         CCCRC and an operator-administered gustatory screening
symptom of SARS-CoV-2 infection, while its positive               test. The novel self-administered test comprised an olfactory
prognostic value is still debated. Five studies investigated      threshold test plus an odour discrimination test and a gusta-
the predictive value of olfactory loss in the diagnosis and       tory screening test with four solutions corresponding to the
course of COVID-19 22,24,26,42,64. It was found that sudden       primary tastes. Although the cohort was made up only of in-
olfactory loss presents a high specificity of 97% and a           fected health personnel and is not representative of the general
sensitivity of 65%, while it has a positive predictive value      population, the preliminary findings appear promising as there
of 63% and negative predictive value of 97% for SARS-             were no significant differences between the results of the tests
CoV-2 infection 24. Interestingly, the use of olfactory loss      for either smell (p = 0.201) or taste (p = 0.180). Pilot data were
as an indicator of COVID-19 in the general population             later confirmed by another study on 300 COVID-19 patients
could have important clinical applications in underserved         belonging to the healthcare staff of the Bellaria-Maggiore
areas with limited access to COVID-19 testing 26. Another         Hospital in Bologna 94.



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Conclusions                                                                  academic production. Acta Biomed 2021;92:e2021207. https://doi.
                                                                             org/10.23750/abm.v92i2.11557
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Conflict of interest statement
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The authors declare no conflict of interest.                                 taste. Laryngoscope 2021;131:1095-1100. https://doi.org/10.1002/
                                                                             lary.29383
Funding                                                                 10
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This research did not receive any specific grant from fund-                  systematic reviews and meta-analyses: the PRISMA statement.
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