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Life
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Olfactory and Gustatory Dysfunctions in COVID‐19 Patients
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Olfactory and Gustatory Dysfunctions in COVID‐19 Patients

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (28 August 2022) | Viewed by 34272

Special Issue Editors

Dr. Luigi Angelo Vaira

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Guest Editor
1. Maxillofacial Surgery Operative Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
2. Biomedical Science Department, PhD School of Biomedical Science, University of Sassari, 07100 Sassari, Italy
Interests: oral and maxillofacial surgery; plastic surgery; otolaryngology
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanna Deiana

E-Mail Website
Guest Editor
Hygiene and Infection Control Unit, Università degli Studi di Sassari, 07100 Sassari, Italy
Interests: preventive medicine; rhinology; anosmia; ageusia; COVID-19
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Salzano

E-Mail Website
Guest Editor
Maxillofacial Surgery Operative Unit, University Hospital of Naples "Federico II", 80131 Naples, Italy
Interests: oral and maxillofacial surgery; plastic surgery; otolaryngology
Special Issues, Collections and Topics in MDPI journals
Dr. Fabio Maglitto

E-Mail Website
Guest Editor
Maxillo-Facial Surgery, University of Naples “Federico II” , 80138 Napoli, Italy
Interests: maxillofacial surgery; rhinology; anosmia; ageusia; COVID-19

Special Issue Information

Dear Colleagues,

Olfactory and gustatory dysfunctions have proven to be one of the most frequent and specific symptoms of COVID-19.

In this Special Issue of Life, we invite researchers from around the world to share their recent research on this topic with us. We are looking for articles that investigate the epidemiological, clinical and pathogenetic aspects of chemosensitive disorders in COVID-19. Furthermore, we are seeking studies on persistent olfactory and gustatory disorders in long-COVID-19, on risk factors for persisting dysfunctions and on the most recent therapeutic advances.

Dr. Luigi Angelo Vaira
Dr. Giovanna Deiana
Dr. Giovanni Salzano
Dr. Fabio Maglitto
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • SARS-CoV-2
  • anosmia
  • ageusia
  • smell
  • taste
  • olfactory dysfunction
  • gustatory dysfunction
  • parosmia
  • phantosmia

Published Papers (15 papers)

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Editorial

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5 pages, 233 KiB  
Editorial
Post-Viral Olfactory Loss: What We Learned from the SARS-CoV-2 Pandemic
by Luigi Angelo Vaira, Giovanna Deiana, Fabio Maglitto and Giovanni Salzano
Life 2022, 12(11), 1868; https://doi.org/10.3390/life12111868 - 12 Nov 2022
Cited by 1 | Viewed by 1189
Abstract
Viral infections have always been one of the most frequent causes of persistent olfactory dysfunctions accounting for 18% to 45% of all cases [...] Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)

Research

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13 pages, 1531 KiB  
Article
Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?
by Arianna Di Stadio, Evanthia Bernitsas, Ignazio La Mantia, Michael J. Brenner, Massimo Ralli, Luigi Angelo Vaira, Andrea Colizza, Carlo Cavaliere, Matteo Laudani, Teresa C. Frohman, Marco De Vincentiis, Elliot M. Frohman and Marta Altieri
Life 2023, 13(1), 226; https://doi.org/10.3390/life13010226 - 13 Jan 2023
Cited by 3 | Viewed by 1892
Abstract
Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical [...] Read more.
Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin’ Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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20 pages, 3871 KiB  
Article
Two-Year Follow-Up on Chemosensory Dysfunction and Adaptive Immune Response after Infection with SARS-CoV-2 in a Cohort of 44 Healthcare Workers
by Sophia E. Schambeck, Laura M. Mateyka, Teresa Burrell, Natalia Graf, Ioana Brill, Thomas Stark, Ulrike Protzer, Dirk H. Busch, Markus Gerhard, Henriette Riehl and Holger Poppert
Life 2022, 12(10), 1556; https://doi.org/10.3390/life12101556 - 07 Oct 2022
Cited by 9 | Viewed by 1924
Abstract
Persistent chemosensory dysfunction (PCD) is a common symptom of long-COVID. Chemosensory dysfunction (CD) as well as SARS-CoV-2-specific antibody levels and CD8+ T-cell immunity were investigated in a cohort of 44 healthcare workers up to a median of 721 days after a positive [...] Read more.
Persistent chemosensory dysfunction (PCD) is a common symptom of long-COVID. Chemosensory dysfunction (CD) as well as SARS-CoV-2-specific antibody levels and CD8+ T-cell immunity were investigated in a cohort of 44 healthcare workers up to a median of 721 days after a positive PCR test. CD was assessed using questionnaires and psychophysical screening tests. After 721 days, 11 of 44 (25%) participants reported PCD, with five describing an impaired quality of life. One participant reported hyperosmia (increased sense of smell). The risk of PCD at 721 days was higher for participants reporting qualitative changes (parosmia (altered smell), dysgeusia (altered taste), or phantosmia (hallucination of smell)) during initial infection than in those with isolated quantitative losses during the first COVID-19 infection (62.5% vs. 7.1%). The main recovery rate occurred within the first 100 days and did not continue until follow-up at 2 years. No correlation was found between antibody levels and CD, but we observed a trend of a higher percentage of T-cell responders in participants with CD. In conclusion, a significant proportion of patients suffer from PCD and impaired quality of life 2 years after initial infection. Qualitative changes in smell or taste during COVID-19 pose a higher risk for PCD. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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13 pages, 1552 KiB  
Article
Chemosensory Dysfunction in Long-Term COVID-19 Assessed by Self-Reported and Direct Psychophysical Methods
by Javier Albayay, Lara Fontana, Valentina Parma and Massimiliano Zampini
Life 2022, 12(10), 1487; https://doi.org/10.3390/life12101487 - 25 Sep 2022
Cited by 4 | Viewed by 1681
Abstract
Chemosensory dysfunction is a frequent postacute sequela of COVID-19. Depending on the type of test used to measure it (self-report vs. direct test), the degree of chemosensory dysfunction in long-term COVID-19 has been found to be highly variable. In this manuscript, we report [...] Read more.
Chemosensory dysfunction is a frequent postacute sequela of COVID-19. Depending on the type of test used to measure it (self-report vs. direct test), the degree of chemosensory dysfunction in long-term COVID-19 has been found to be highly variable. In this manuscript, we report the cross-sectional data (first assessment) of a longitudinal study (6-month follow-up) examining smell, taste, and chemesthesis in participants affected by long-term COVID-19 (COVID+) and participants without COVID-19 (COVID−) by means of both self-reported and direct psychophysical methods. In total, 208 Italian participants (COVID+ n = 133; COVID− n = 75) completed the Smell and Taste Check developed by the Global Consortium for Chemosensory Research (GCCR), which includes self-reports on smell, taste, and chemesthetic abilities as well as direct intensity ratings of unstandardized smell, taste, and chemesthetic household items. Furthermore, all participants completed SCENTinel, a validated direct smell test. We found a positive association between the self-reported, unstandardized direct test and the validated direct test for smell, indicating moderate to large agreement across measures. Furthermore, the performance on SCENTinel was significantly associated with self-reported smell loss. A positive association between the self-reports and the intensity of household items was also retrieved for taste and chemesthesis. The time relative to COVID-19 onset (267.3 ± 113.9 days) did not modulate the chemosensory performance of self-reported abilities, intensity ratings, and SCENTinel. All in all, we confirm the impairment of three chemical senses (smell, taste, and chemesthesis) in an independent sample of Italian participants affected by long-term COVID-19 by using and comparing self-reported and direct psychophysical methods. We contribute to the discussion on best practices to monitor chemosensory dysfunction in individuals affected by long-term COVID-19. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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7 pages, 585 KiB  
Article
Topical Administration of Mometasone Is Not Helpful in Post-COVID-19 Olfactory Dysfunction
by Constantin A. Hintschich, Melanie Dietz, Antje Haehner and Thomas Hummel
Life 2022, 12(10), 1483; https://doi.org/10.3390/life12101483 - 24 Sep 2022
Cited by 11 | Viewed by 1648
Abstract
Persistent olfactory dysfunction is a major concern post-COVID-19, affecting up to 5% of all patients. Different therapeutic options, including mometasone nasal spray, have been recommended, only some of which have been validated for post-COVID-19 olfactory dysfunction. In this study we psychophysically assessed the [...] Read more.
Persistent olfactory dysfunction is a major concern post-COVID-19, affecting up to 5% of all patients. Different therapeutic options, including mometasone nasal spray, have been recommended, only some of which have been validated for post-COVID-19 olfactory dysfunction. In this study we psychophysically assessed the effect of intranasally applied mometasone furoate on the recovery of olfaction. The spray was applied with a long applicator so that the olfactory cleft could be reached effectively. After olfactory dysfunction had been confirmed psychophysically using Sniffin’ Sticks, patients were randomly assigned to two different treatment arms: the study group (n = 40) underwent olfactory training and intranasal administration of mometasone furoate twice daily, whereas the control group (n = 46) performed olfactory training only. After a study duration of three months, psychophysical testing of olfaction was repeated using Sniffin’ Sticks. We found no benefit of an additional topical administration of mometasone furoate compared to olfactory training alone. These results psychophysically confirm two previous studies which were based on patients’ subjective self-ratings. Our findings are in contrast to current recommendations for the management of olfactory dysfunction post-COVID-19, which might have to be adapted accordingly. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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14 pages, 1903 KiB  
Article
COVID-19 Smell Impairment and Crosstalk with Hypoxia Physiology
by Andrea Mazzatenta, Margherita Maffei, Camillo Di Giulio and Giampiero Neri
Life 2022, 12(9), 1408; https://doi.org/10.3390/life12091408 - 09 Sep 2022
Cited by 1 | Viewed by 1441
Abstract
Since its apomorphic appearance in 2019, severe acute respiratory syndrome Coronavirus type 2 (SARS-CoV-2) nowadays circulates as a plesiomorphic human virus in several synapomorphic variants. The respiratory tract is the most important site of infection, the viral effects in the lungs are well [...] Read more.
Since its apomorphic appearance in 2019, severe acute respiratory syndrome Coronavirus type 2 (SARS-CoV-2) nowadays circulates as a plesiomorphic human virus in several synapomorphic variants. The respiratory tract is the most important site of infection, the viral effects in the lungs are well described, and more than half of the patients could develop shortness of breath and dyspnea and require ventilatory support. The physiological sign of this condition is the decrease in the partial pressure of oxygen in the blood, leading to acute hypoxia, which could be a factor in the disease. In severe patients, we recorded several physiological parameters: breath frequency (BF), partial pressure of oxygen in the blood (pO2), partial pressure of carbon dioxide in the blood (pCO2), hemoglobin (Hb), heart rate (HR), and blood pressure in correlation with the olfactory threshold. We found significant correlations between reduced olfactory threshold with pO2 and hemoglobin levels, changes in heart rate, and increased HR and pCO2. These results suggest that COVID-19 causes an impaired sense of smell that decreases in threshold corresponding to the disease severity. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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17 pages, 882 KiB  
Article
Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients
by María A. Callejón-Leblic, Daniel I. Martín-Jiménez, Ramón Moreno-Luna, Jose M. Palacios-Garcia, Marta Alvarez-Cendrero, Julissa A. Vizcarra-Melgar, Carlos Fernandez-Velez, Isabel M. Reyes-Tejero, Juan Maza-Solano, Jaime Gonzalez-Garcia, Beatriz Tena-García, María E. Acosta-Mosquera, Alfonso Del Cuvillo and Serafín Sánchez-Gómez
Life 2022, 12(8), 1256; https://doi.org/10.3390/life12081256 - 17 Aug 2022
Cited by 13 | Viewed by 2114
Abstract
Background: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. Methods: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of [...] Read more.
Background: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. Methods: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. Results: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = −0.36, p = 0.0027). Conclusion: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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Graphical abstract

11 pages, 1703 KiB  
Article
Unmasking the ‘Asymptomatic’ COVID-19: A Nose Question
by Andrea Mazzatenta, Anna Berardi, Gabriele Alessandro Novarria and Giampiero Neri
Life 2022, 12(8), 1248; https://doi.org/10.3390/life12081248 - 16 Aug 2022
Cited by 4 | Viewed by 1498
Abstract
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has high infectivity, often masked by asymptomatic carriers, which allows it to spread rapidly and become a pandemic. Attempts to slow the pandemic at this stage depend on the ability to unmask asymptomatic [...] Read more.
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has high infectivity, often masked by asymptomatic carriers, which allows it to spread rapidly and become a pandemic. Attempts to slow the pandemic at this stage depend on the ability to unmask asymptomatic carriers. The rapid diagnosis of active coronavirus disease 2019 (COVID-19) infection is one of the cornerstones of pandemic control, as the nasal cavity is the main gateway for SARS-CoV-2 entry and altered sense of smell is a feature of the current virus. In the present study, we therefore tested the olfactory threshold coupled with heart–lung parameters in subjects undergoing traditional molecular testing, resulting in a significantly different score between asymptomatic subjects and healthy controls. In total, 82% of asymptomatic positives showed olfactory impairment; of these, 46% had severe hyposmia and 7% had anosmia, while in the control 9% had severe hyposmia and 0% had anosmia, respectively, which agrees with heart rate, breathing rate, and blood pressure parameter variations. The olfactory test coupled with physiological parameters may help to identify asymptomatic people. In conclusion, our results suggest that most asymptomatic individuals could be unmasked by mass olfactory rapid threshold screening and then referred to traditional slower diagnostic tests. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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16 pages, 1473 KiB  
Article
Anosmia Testing as Early Detection of SARS-CoV-2 Positivity; A Prospective Study under Screening Conditions
by Frederic Jungbauer, Catharina Gerhards, Margot Thiaucourt, Michael Behnes, Nicole Rotter, Angela Schell, Verena Haselmann, Michael Neumaier and Maximilian Kittel
Life 2022, 12(7), 968; https://doi.org/10.3390/life12070968 - 28 Jun 2022
Cited by 2 | Viewed by 1465
Abstract
Sudden onset of anosmia is a phenomenon often associated with developing COVID-19 disease and has even been described as an initial isolated symptom in individual cases. In this case-control study, we investigated the feasibility of this condition as a suitable screening test in [...] Read more.
Sudden onset of anosmia is a phenomenon often associated with developing COVID-19 disease and has even been described as an initial isolated symptom in individual cases. In this case-control study, we investigated the feasibility of this condition as a suitable screening test in a population at risk. We performed a prospective study with a total of 313 subjects with suspected SARS-CoV-2 infection. In parallel to routine PCR analysis, a modified commercial scent test was performed to objectify the presence of potential anosmia as a predictor of SARS-CoV-2 positivity. Furthermore, a structured interview assessment of the participants was conducted. A total of 12.1% of the study participants had molecular genetic detection of SARS-CoV-2 infection in the nasopharyngeal swab. It could be demonstrated that these subjects had a significantly weaker olfactory identification performance of the scents. Further analysis of the collected data from the scent test and medical history via random forest (Boruta) algorithm showed that no improvement of the prediction power was achieved by this design. The assay investigated in this study may be suitable for screening general olfactory function. For the screening of COVID-19, it seems to be affected by too many external and internal biases and requires too elaborate and selective pre-test screening. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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12 pages, 1463 KiB  
Article
Asthma and Cacosmia Could Be Predictive Factors of Olfactory Dysfunction Persistence 9 Months after SARS-CoV-2 Infection: The ANOSVID Study
by Can Tipirdamaz, Souheil Zayet, Molka Osman, Julien Mercier, Elodie Bouvier, Vincent Gendrin, Kévin Bouiller, Quentin Lepiller, Lynda Toko, Alix Pierron, Pierre-Yves Royer, Pauline Garnier, N’dri-Juliette Kadiane-Oussou, Catherine Chirouze and Timothée Klopfenstein
Life 2022, 12(7), 929; https://doi.org/10.3390/life12070929 - 21 Jun 2022
Cited by 6 | Viewed by 1434
Abstract
Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent [...] Read more.
Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent OD (p-OD group) in comparison with patients with resolved OD (r-OD group). Results. Among 354 COVID-19 patients, 229 reported OD were included. Eighty-five percent of patients (n = 195) recovered from their OD within 90 days. However, 9.5 months (in average) after symptoms onset, OD were persisting in 93 patients (40.6%) and resolved in 136 patients (59.4%). In the p-OD group (n = 93), the mean age was 51.4 years (19–98) ± 20.2, and 65 patients (69.9%) were female; the three main comorbidities in the p-OD group were: asthma (20.4%, n = 19), allergic rhinitis (19.4%, n = 18), and arterial hypertension (16.1%, n = 15). Eleven patients (12%) presented anosmia, and 82 patients (88%) presented hyposmia. Asthma was more described in p-OD group than r-OD group (19 (20.4%) versus 10 (7.4%), p = 0.006). Cacosmia was more described in p-OD group than r-OD group (27 (29.0%) versus 18 (13.2%), p = 0.005). There was no significant difference between the two groups concerning other comorbidities and symptoms, clinical, biological, and imaging findings, and outcome or about the impact of OD on the quality of life of the patients between the p-OD group and r-OD group. sQOD-NS brief version score was 10.7 ± 5.89 and 12.0 ± 6.03, respectively (p = 0.137). Conclusion. Forty-one percent of patients with OD reported OD persistence 9.5 months after COVID-19 (hyposmia in 88% of cases). Asthma and cacosmia could be predictive factors of OD persistence. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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8 pages, 457 KiB  
Article
SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses
by Antje Haehner, Belinda Marquardt, Romina Kardashi, Katja de With, Susann Rößler, Basile Nicolas Landis, Antje Welge-Luessen and Thomas Hummel
Life 2022, 12(3), 461; https://doi.org/10.3390/life12030461 - 21 Mar 2022
Cited by 17 | Viewed by 2130
Abstract
The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient [...] Read more.
The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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13 pages, 1118 KiB  
Article
The Effects of Persistent Olfactory and Gustatory Dysfunctions on Quality of Life in Long-COVID-19 Patients
by Luigi Angelo Vaira, Claudia Gessa, Giovanna Deiana, Giovanni Salzano, Fabio Maglitto, Jerome R. Lechien, Sven Saussez, Pasquale Piombino, Andrea Biglio, Federico Biglioli, Paolo Boscolo-Rizzo, Claire Hopkins, Valentina Parma and Giacomo De Riu
Life 2022, 12(2), 141; https://doi.org/10.3390/life12020141 - 19 Jan 2022
Cited by 40 | Viewed by 4318
Abstract
(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to [...] Read more.
(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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Review

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11 pages, 718 KiB  
Review
SARS-CoV-2 Infection and Taste Alteration: An Overview
by Gaetano Scotto, Vincenzina Fazio, Eleonora Lo Muzio, Lorenzo Lo Muzio and Francesca Spirito
Life 2022, 12(5), 690; https://doi.org/10.3390/life12050690 - 06 May 2022
Cited by 17 | Viewed by 2467
Abstract
Since the worldwide spread of SARS-CoV-2 infection, the management of COVID-19 has been a challenge for healthcare professionals. Although the respiratory system has primarily been affected with symptoms ranging from mild pneumonia to acute respiratory distress syndrome, other organs or systems have also [...] Read more.
Since the worldwide spread of SARS-CoV-2 infection, the management of COVID-19 has been a challenge for healthcare professionals. Although the respiratory system has primarily been affected with symptoms ranging from mild pneumonia to acute respiratory distress syndrome, other organs or systems have also been targets of the virus. The mouth represents an important route of entry for SARS-CoV-2. Cells in the oral epithelium, taste buds, and minor and major salivary glands express cellular entry factors for the virus, such as ACE2, TMPRSS2 and Furin. This leads to symptoms such as deterioration of taste, salivary dysfunction, mucosal ulcers, before systemic manifestation of the disease. In this review we report and discuss the prevalence and socio-demographics of taste disturbances in COVID-19 patients, analysing the current international data. Importantly, we also take stock of the various hypothesized pathogenetic mechanisms and their impact on the reported symptoms. The literature indicated that COVID-19 patients frequently present with gustatory dysfunction, whose prevalence varies by country, age and sex. Furthermore, this dysfunction also has a variable duration in relation to the severity of the disease. The pathogenetic action is intricately linked to viral action which can be expressed in several ways. However, in many cases these are only hypotheses that need further confirmation. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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26 pages, 2667 KiB  
Review
Gustatory and Saliva Secretory Dysfunctions in COVID-19 Patients with Zinc Deficiency
by Hironori Tsuchiya
Life 2022, 12(3), 353; https://doi.org/10.3390/life12030353 - 28 Feb 2022
Cited by 13 | Viewed by 4057
Abstract
Given the ever-progressing studies on coronavirus disease 2019 (COVID-19), it is critical to update our knowledge about COVID-19 symptomatology and pathophysiology. In the present narrative review, oral symptoms were overviewed using the latest data and their pathogenesis was hypothetically speculated. PubMed, LitCovid, ProQuest, [...] Read more.
Given the ever-progressing studies on coronavirus disease 2019 (COVID-19), it is critical to update our knowledge about COVID-19 symptomatology and pathophysiology. In the present narrative review, oral symptoms were overviewed using the latest data and their pathogenesis was hypothetically speculated. PubMed, LitCovid, ProQuest, and Google Scholar were searched for relevant studies from 1 April 2021 with a cutoff date of 31 January 2022. The literature search indicated that gustatory dysfunction and saliva secretory dysfunction are prevalent in COVID-19 patients and both dysfunctions persist after recovery from the disease, suggesting the pathogenic mechanism common to these cooccurring symptoms. COVID-19 patients are characterized by hypozincemia, in which zinc is possibly redistributed from blood to the liver at the expense of zinc in other tissues. If COVID-19 induces intracellular zinc deficiency, the activity of zinc-metalloenzyme carbonic anhydrase localized in taste buds and salivary glands may be influenced to adversely affect gustatory and saliva secretory functions. Zinc-binding metallothioneins and zinc transporters, which cooperatively control cellular zinc homeostasis, are expressed in oral tissues participating in taste and saliva secretion. Their expression dysregulation associated with COVID-19-induced zinc deficiency may have some effect on oral functions. Zinc supplementation is expected to improve oral symptoms in COVID-19 patients. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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27 pages, 2134 KiB  
Review
Exploring the Clinical Utility of Gustatory Dysfunction (GD) as a Triage Symptom Prior to Reverse Transcription Polymerase Chain Reaction (RT-PCR) in the Diagnosis of COVID-19: A Meta-Analysis and Systematic Review
by Khang Wen Pang, Sher-Lyn Tham and Li Shia Ng
Life 2021, 11(12), 1315; https://doi.org/10.3390/life11121315 - 29 Nov 2021
Cited by 2 | Viewed by 3021
Abstract
Background: The diagnosis of COVID-19 is made using reverse transcription polymerase chain reaction (RT-PCR) but its sensitivity varies from 20 to 100%. The presence of gustatory dysfunction (GD) in a patient with upper respiratory tract symptoms might increase the clinical suspicion of COVID-19. [...] Read more.
Background: The diagnosis of COVID-19 is made using reverse transcription polymerase chain reaction (RT-PCR) but its sensitivity varies from 20 to 100%. The presence of gustatory dysfunction (GD) in a patient with upper respiratory tract symptoms might increase the clinical suspicion of COVID-19. Aims: To perform a systematic review and meta-analysis to determine the pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−) and diagnostic odds ratio (DOR) of using GD as a triage symptom prior to RT-PCR. Methods: PubMed and Embase were searched up to 20 June 2021. Studies published in English were included if they compared the frequency of GD in COVID-19 adult patients (proven by RT-PCR) to COVID-19 negative controls in case control or cross-sectional studies. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies. Results: 21,272 COVID-19 patients and 52,298 COVID-19 negative patients were included across 44 studies from 21 countries. All studies were of moderate to high risk of bias. Patients with GD were more likely to test positive for COVID-19: DOR 6.39 (4.86–8.40), LR+ 3.84 (3.04–4.84), LR− 0.67 (0.64–0.70), pooled sensitivity 0.37 (0.29–0.47) and pooled specificity 0.92 (0.89–0.94). While history/questionnaire-based assessments were predictive of RT-PCR positivity (DOR 6.62 (4.95–8.85)), gustatory testing was not (DOR 3.53 (0.98–12.7)). There was significant heterogeneity among the 44 studies (I2 = 92%, p < 0.01). Conclusions: GD is useful as a symptom to determine if a patient should undergo further testing, especially in resource-poor regions where COVID-19 testing is scarce. Patients with GD may be advised to quarantine while repeated testing is performed if the initial RT-PCR is negative. Funding: None. Full article
(This article belongs to the Special Issue Olfactory and Gustatory Dysfunctions in COVID‐19 Patients)
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