Characteristics of Chemosensory Perception in Long COVID and COVID Reinfection.

Emerging data suggest an increasing prevalence of persistent symptoms in individuals affected by coronavirus disease-19 (COVID-19). The objective of this study was to determine the relative frequency of altered taste and smell in COVID reinfection (multiple COVID positive tests) and long COVID (one COVID positive test). We sent an electronic survey to patients in the Indiana University Health COVID registry with positive COVID test results, querying if they were experiencing symptoms consistent with long COVID including altered chemosensory perceptions. Among the 225 respondents, a greater long COVID burden and COVID reinfection was observed in women. Joint pain was reported as the most common symptom experienced by 18% of individuals in the long COVID cohort. In the COVID reinfection cohort >20% of individuals reported headache, joint pain, and cough. Taste perception worse than pre-COVID was reported by 29% and 42% of individuals in the long COVID and COVID reinfection cohorts, respectively. Smell perception worse than pre-COVID was reported by 37% and 46% of individuals in long COVID and COVID reinfection cohorts, respectively. Further, Chi-square test suggested significant association between pre-COVID severity of taste/smell perception and headache in both cohorts. Our findings highlight the prevalence of persistent chemosensory dysfunction for two years and longer in long COVID and COVID reinfection.

SARS-CoV-2 Effects on Psychophysical Olfactory Scores: Prospective Study With Evaluation Before and 60-Days After Infection.

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin' Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

SARS-CoV-2 recombinant spike protein induces cell apoptosis in rat taste buds.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause loss or alteration of taste and smell as early symptoms or sequelae, but the detailed mechanism behind this phenomenon remains unclear. Here, we investigated whether the SARS-CoV-2 spike protein induces taste cell apoptosis and expression of the apoptosis-related cytokine TNF-α in male Sprague-Dawley rats. Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-fluorescein nick end labeling (TUNEL) assay results revealed a significantly higher apoptosis index for taste cells in the SARS-CoV-2 group than for those in the control group. An immunohistochemistry analysis indicated significantly more TNF-α-positive cells in the SARS-CoV-2 group compared with the control group. These data suggest that the SARS-CoV-2 spike protein promotes taste cell apoptosis and the release of apoptosis-related cytokine TNF-α, implicating its contribution to the taste malfunction caused by coronavirus disease 2019 (COVID-19).

The Prevalence and Pathophysiology of Chemical Sense Disorder Caused by the Novel Coronavirus.

Emerging viral infections are a ceaseless challenge and remain a global public health concern. The world has not yet come back to normal from the devastating effects of the highly contagious and pathogenic novel coronavirus, or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Olfactory and taste dysfunction is common in patients infected by the novel coronavirus. In light of the emergence of different coronavirus variants, it is important to update the prevalence and pathophysiology of these side effects. In this review, articles published on the prevalence of olfactory and taste dysfunction from coronavirus disease (COVID-19) and their possible pathophysiologic mechanisms have been reviewed and reported. The modulatory role of different SARS-CoV-2 variants on the chemical senses is then described. The clinical relevance of chemical sense disorder and its long-term morbidity and management is also discussed.

Prevalence of smell and taste dysfunction in patients infected with COVID-19

Purpose: This study aims to evaluate olfactory and gustatory dysfunctions (OGDs) in COVID-19 patients according to hospital admission type and possible risk factors for OGD. Materials and Methods: This study included 200 adult patients who were diagnosed with COVID-19 between January 2021 and September 2021. Patients were separated into two groups. The first group comprised 100 patients who applied to pandemic outpatient clinics with a milder course and were isolated at home. The second group comprised 100 patients with a more severe clinical course hospitalized in the pandemic ward. Patients completed a data form in which olfactory and gustatory functions and various clinical information were inquired about and rated their smell and taste dysfunction using a visual analog scale (VAS). Results: In the ambulatory group, 72% of patients were female and the mean age was 39.6 +/- 13.2 years. In the admitted group, 50% of patients were female, and the mean age was 52.4 +/- 11.0 years. The most common symptoms in all patients were loss of taste (41%) and smell (45.5%). Females and younger individuals were significantly more likely to have OGD. OGD was more common in the ambulatory group. Smell/taste VAS scores were significantly lower in the ambulatory group. Conclusion: OGD is associated with various mechanisms depending on the increased inflammatory response in the early stages of COVID-19. OGD appears to be the key symptom and diagnostic indicator and should be inquired about. It should be kept in mind that the frequency of OGD may differ according to age and gender.

COVID-19 Induced Taste Dysfunction and Recovery: Association with Smell Dysfunction and Oral Health Behaviour.

Background and Objectives: Disruption to taste and smell are common symptoms of COVID-19 infection. The current literature overlooks taste symptoms and tends to focus on the sense of smell. Persisting cases (>28 days) of taste dysfunction are increasingly recognised as a major future healthcare challenge. This study focuses on the severity and recovery of COVID-19 induced taste loss and association with olfactory symptoms, lifestyle and oral health factors. Materials and Methods: This study was a cross-sectional survey comparing 182 rapid taste recovery participants (≤28 days) with 47 participants with prolonged taste recovery >28 days. Analyses of taste loss in association with smell loss, age, sex, illness severity, diet, BMI, vitamin-D supplementation, antidepressants, alcohol use, smoking, brushing frequency, flossing, missing teeth, appliances and number of dental restorations were conducted. Differences in the severity of the loss of sour, sweet, salt, bitter and umami tastes were explored. Results: Both the severity and the duration of taste and smell loss were closely correlated (p < 0.001). Salt taste was significantly less affected than all other taste qualities (p < 0.001). Persisting taste loss was associated with older age (mean ± 95% CI = 31.73 ± 1.23 years vs. 36.66 ± 3.59 years, p < 0.001) and reduced likelihood of using floss (odds ratio ± 95% CI = 2.22 (1.15-4.25), p = 0.047). Conclusions: Smell and taste loss in COVID-19 are closely related, although a minority of individuals can experience taste or smell dysfunction in the absence of the other. The taste of salt may be less severely affected than other taste qualities and future work exploring this finding objectively is indicated. The association of flossing with rapid taste recovery adds to the growing evidence of a link between good periodontal health and favourable COVID-19 outcomes.

SARS-CoV-2 recombinant proteins-induced degeneration of taste buds in rat circumvallate papillae.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause loss or alteration of taste and smell as early symptoms and sequelae, but the detailed mechanism remains unclear. This study investigated whether coronavirus disease 2019-induced taste disorders are caused by direct effects on taste bud cells. SARS-CoV-2 recombinant spike and nucleocapsid proteins were applied to circumvallate papillae of male Sprague-Dawley rats. Immunohistochemistry and image analysis were used to compare the number of taste buds, and taste bud cells and area, together with confirmation of angiotensin-converting enzyme 2 (ACE2) expression. Immunohistochemical analysis revealed ACE2 expression in the taste buds of rat circumvallate papillae. Decreases in the number of taste buds, taste bud cells, and their area were observed at 12 days after application of SARS-CoV-2 recombinant spike and nucleocapsid proteins. These data suggest that SARS-CoV-2 proteins induce degeneration of taste buds.

Persistent Parosmia Caused By COVID-19 Infection: An Emerging Symptom.

Objectives Coronavirus disease 2019 (COVID-19) is associated with several known signs and symptoms, including olfactory disturbances leading to anosmia and parosmia. This study aimed to evaluate the clinical features of the emerging symptoms of post-COVID-19 parosmia and to report the outcome of commonly used intervention methods. Methods The study's sample included post-COVID-19 patients who complained of parosmia, presented to otorhinolaryngology clinics at private tertiary care hospitals from December 2020 to April 2021. Patients' data were collected from the hospital system and through direct phone interviews. The Modified Arabic 20-Items Sino-Nasal Outcome Test (MA-SNOT-20) was used to measure the severity of rhinosinusitis symptoms. Results Twenty-one patients were included in the study, and their ages mainly ranged between 20 and 39 years (76.2%), predominantly females 19 (90.5%). Post the COVID-19 illness course, nearly half of the patients (9; 42.9%) reported full recovery of olfaction and taste senses. Nine cases (42.9%) received treatment with intranasal and oral steroids, of which only three cases (14.3%) noticed improvement. The remaining 12 cases (57.1%) did not receive any treatment, two of which improved (9.5%). The maximum MA-SNOT score was 37 while the minimum was 3, and eight patients (38.1%) scores were between one and 10 points. Conclusion Olfactory and taste dysfunctions are common symptoms of COVID-19. The emerging symptom of parosmia is worth reporting in the literature to increase the awareness of this particular symptom in this pandemic era. Many management strategies have been introduced that might be effective. However, further studies are needed to establish evidence-based management protocols.

Prevalence of Smell or Taste Dysfunction Among Children With COVID-19 Infection: A Systematic Review and Meta-Analysis.

Background: Smell and taste dysfunctions are common and have been reported as an early indicator of COVID-19. The prevalence of smell and taste dysfunctions among children with COVID-19 varies greatly across studies, which remains to be summarized quantitatively. This review aimed at examining the pooled prevalence of smell or taste dysfunctions among children with COVID-19, summarizing possible causes of the inconsistencies in the current estimates. Methods: Systematic searches of databases were conducted for literature published until 12 January 2021. Statistical analyses were performed using R software, the pooled prevalence was combined using random effects model. The Loney criteria were used for quality assessment. Results: A total of 18 eligible studies were included. The results showed that the pooled prevalence of smell dysfunction among children with COVID-19 was 15.97% (95% CI: 8.18-23.77%), the pooled prevalence of taste dysfunction among children with COVID-19 was 9.20% (95% CI: 4.25-14.16%), the pooled prevalence of smell or taste dysfunction among children with COVID-19 was 15.50% (95% CI: 10.30-20.70%) and the pooled prevalence of smell and taste dysfunction among children with COVID-19 was 20.21% (95% CI: 14.14-26.28%). Higher smell or taste dysfunction rates were associated with being female, younger age, smaller sample size, patients in Asia, and with comorbidities. Conclusions: Evidence suggests that smell or taste dysfunctions were common among children with COVID-19. Further research is needed to identify effective strategies for preventing and treating smell and taste dysfunctions among children with COVID-19.

High frequency of smell and taste dysfunctions in allergy health care professionals suffering from COVID-19.

BACKGROUND AND OBJECTIVE: Since the first stages of the novel coronavirus 2019 (SARS-CoV-2) outbreak smell and/or taste dysfunction (STD), has been described from 5% to 88% in COVID-19 patients. Objective: we aimed to assess STD in healthcare professionals (HCP), mainly allergists, affected with COVID-19, by means of a survey, and to evaluate the association of STD and their severity with demographic characteristics, symptoms, comorbidities, and hospital admission. METHODS: A 15-item questionnaire was designed including different sections as follows: demographics, diagnostic characteristics, STD patterns, medication use as well as comorbidities. The questionnaire was developed using Google forms, implemented and distributed to members of the Spanish Society of Allergology and Clinical Immunology (SEAIC) and spread via Social Media to be completed by HCP affected with COVID-19. RESULTS: HCP (n=234), 76.5% ≤55 yrs, 73.5% female, completed the survey. There was STD in up to 74.4% of the respondents, 95.6% reporting a moderate-severe impairment. Mean recovery time of taste dysfunction was 21.6±24.0 days in HCP ≤55 yrs and 33.61±26.2 days in >55 yrs (p=0.019). Stratified analysis by severity of STD showed that more than a half of COVID-19 subjects presented severe loss of smell. An older age (>55 yrs) was associated with fever, anorexia, less headache and with a longer persistence of taste dysfunction. CONCLUSIONS: STD is a common symptom in COVID-19, even as a unique or preceding symptom. HCP who declared smell dysfunction (SD) were younger than those not affected with STD. Taste dysfunction (TD) may imply more systemic involvement in COVID-19-positive HCP.

Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence.

BACKGROUND: Smell dysfunction has been recognized as an early symptom of SARS-CoV-2 infection, often occurring before the onset of core symptoms of the respiratory tract, fever or muscle pain. In most cases, olfactory dysfunction is accompanied by reduced sense of taste, is partial (microsmia) and seems to normalize after several weeks, however, especially in cases of virus-induced complete smell loss (anosmia), there are indications of persisting deficits even 2 months after recovery from the acute disease, pointing towards the possibility of chronic or even permanent smell reduction for a significant part of the patient population. To date, we have no knowledge on the specificity of anosmia towards specific odorants or chemicals and about the longer-term timeline of its persistence or reversal. METHODS: In this longitudinal study, 70 participants from a community in Lower Austria that had been tested positive for either IgG or IgM SARS-CoV-2 titers in June 2020 and a healthy control cohort (N = 348) underwent smell testing with a 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT). The test was performed in October 2020, i.e. 4 months after initial diagnosis via antibody testing. Results were analyzed using statistical tests for contingency for each smell individually in order to detect whether reacquisition of smell is dependent on specific odorant types. RESULTS: For all odorants tested, except the odor "smoke", even 4 months or more after acute SARS-CoV-2 infection, participants with a positive antibody titer had a reduced sense of smell when compared to the control group. On average, while the control cohort detected a set of 12 different smells with 88.0% accuracy, the antibody-positive group detected 80.0% of tested odorants. A reduction of accuracy of detection by 9.1% in the antibody-positive cohort was detected. Recovery of the ability to smell was particularly delayed for three odorants: strawberry (encoded by the aldehyde ethylmethylphenylglycidate), lemon (encoded by citronellal, a monoterpenoid aldehyde), and soap (alkali metal salts of the fatty acids plus odorous additives) exhibit a sensitivity of detection of an infection with SARS-CoV-2 of 31.0%, 41.0% and 40.0%, respectively. CONCLUSION: Four months or more after acute infection, smell performance of SARS-CoV-2 positive patients with mild or no symptoms is not fully recovered, whereby the ability to detect certain odors (strawberry, lemon and soap) is particularly affected, suggesting the possibility that these sensitivity to these smells may not only be lagging behind but may be more permanently affected.

Characteristics of taste dysfunction in COVID-19 subjects coming from two different countries.

Taste dysfunction (TD) has been recognised, together with olfactory dysfunction, as a key presenting symptom of COVID-19. The capability to recognise flavours, flavour intensities and aroma characteristics can be highly variable within the same population, as well as potentially diverse between culturally different populations. The aims of this study are to evaluate whether a difference in the types of TD presentation amongst COVID-19 positive subjects can be demonstrated and whether a difference exists between populations of different cultures.

Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.

OBJECTIVES: To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis. METHODS: Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua. RESULTS: Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell (P = .04 and P = .02) and taste recovery (P = .02 and P = .01). Ethnicity (being white) showed to positively influence only taste recovery (P = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs (P = .02 and P = .011, respectively). Working on a COVID-19 ward did not influence prognosis. CONCLUSIONS: The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity. LEVEL OF EVIDENCE: 4.

The Loss of Smell and Taste in the COVID-19 Outbreak: a Tale of Many Countries.

PURPOSE OF REVIEW: Olfactory dysfunction in upper airway viral infections (common cold, acute rhinosinusitis) is common (> 60%). During the COVID-19 outbreak, frequency of sensory disorders (smell and/or taste) in affected patients has shown a high variability from 5 to 98%, depending on the methodology, country, and study. RECENT FINDINGS: A sudden, severe, isolated loss of smell and/or taste, in the absence of other upper airway inflammatory diseases (allergic rhinitis, chronic rhinosinusitis, nasal polyposis), should alert individuals and physicians on being potentially affected by COVID-19. The evaluation of smell/taste disorders with a visual analogue scale or an individual olfactory or gustatory test, at the hospital or by telemedicine, to prevent contamination might facilitate an early detection of infected patients and reduce the transmission of SARS-CoV-2. During the COVID-19 outbreak, patients with sudden loss of smell should initiate social distancing and home isolation measures and be tested for SARS-CoV-2 diagnostic test when available. Olfactory training is recommended when smell does not come back after 1 month but can be started earlier.