How COVID-19 brought smell disorders in the spotlight

The rapid spread of the COVID-19 infection required prompt recognition and immediate isolation of patients. In the evolution of the disease various symptoms were indicated as suggestive of a SARS-CoV-2 infection, among them being also described anosmia and ageusia. In order to review how olfactory disorders are related to COVID-19 disease, we carried out an analysis by searching PubMed, Science Direct, Springer, and LILACS. The research was made using MeSH descriptors and the Boolean operator, “AND”, for the terms “olfactory disorders” or “olfactory dysfunction” or “anosmia” or “neurologic manifestations” or “ENT symptoms” AND “COVID-19” or “SARS-CoV-2” or “coronavirus infections”, with a filter on the publication date set for 01.01.2020 – 18.06.2021. A total of 956 articles were found in the databases, out of which 14 were included in the study. The statistics suggest that alterations of the chemosensory function are strongly correlated with COVID-19, although the exact pathophysiologic mechanism is not well established. Symptomatology suggestive of chemosensory dys-function (smell primarily and then taste alterations) elevate the degree of suspicion of a SARS-CoV-2 infection and they commend prompt isolation and surveillance measurements.

Olfactory-related Quality of Life Adjustments in Smell Loss during the Coronavirus-19 Pandemic

Background Previous studies provided the first evidence that the importance of olfaction decreases with the duration of olfactory dysfunction (OD). Objective To evaluate differences in olfactory-related quality of life (QoL) between patients with new-onset and persistent smell loss (>4 weeks) during the coronavirus-19 (COVID-19) pandemic and patients with persistent postinfectious OD (PIOD) that were recruited before the pandemic. Methods This was a retrospective study that included 149 patients with self-reported OD. The olfactory-related QoL was measured using the questionnaire of OD (QOD). The QOD measures the degree to which patients (i) adjust and cope with smell loss (QOD-positive statement [QOD-PS]), (ii) suffer from distorted odor perceptions (QOD-parosmia [QOD-PAR]), and (iii) suffer from smell loss in general (QOD-negative statement [QOD-NS]). Self-perceived chemosensory function, demographics, olfactory function, and duration of smell loss were evaluated. Analyses of variance were used to depict differences in QoL-outcomes between different OD groups. Results All patients included during the COVID-19 pandemic reported an extensive loss of chemosensory functions of smell, taste, and flavor perception. Psychophysical retronasal screening testing showed olfactory impairments in more than half of these patients. One-way analysis of variance and posthoc tests revealed that the QOD-NS was significantly higher in the new-onset OD group than the PIOD group. At the same time, the QOD-PS score was significantly higher in the PIOD and the persistent COVID-19 OD group than in the new-onset OD group. Conclusion We showed that patients with persistent OD experienced better olfactory-related adjustment and lower QoL-impairment scores than those with recent-onset smell loss, suggesting that the olfactory-related QoL might change as a function of time after symptom onset.

Quantitative but not qualitative flavor recognition impairments in COVID-19 patients

Background Smell and taste dysfunctions (STDs) are symptoms associated with COVID-19 syndrome, even if their incidence is still uncertain and variable. Aims In this study, the effects of SARS-CoV-2 infection on chemosensory function have been investigated using both a self-reporting questionnaire on smell and flavor perception, and a simplified flavor test. Methods A total of 111 subjects (19 hospitalized [HOS] and 37 home-isolated [HI] COVID-19 patients, and 55 healthy controls [CTRL]) were enrolled in the study. They received a self-evaluation questionnaire and a self-administered flavor test kit. The flavor test used consists in the self-administration of four solutions with a pure olfactory stimulus (coffee), a mixed olfactory-trigeminal stimulus (peppermint), and a complex chemical mixture (banana). Results After SARS-CoV-2 infection, HOS and HI patients reported similar prevalence of STDs, with a significant reduction of both smell and flavor self-estimated perception. The aromas of the flavor test were recognized by HI and HOS COVID-19 patients similarly to CTRL; however, the intensity of the perceived aromas was significantly lower in patients compared to controls. Conclusion Data reported here suggests that a chemosensory impairment is present after SARS-CoV-2 infection, and the modified “flavor test” could be a novel self-administering objective screening test to assess STDs in COVID-19 patients. Clinical trial registration no. NCT04840966; April 12, 2021, retrospectively registered

High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: a matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation

Background: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. Methodology: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. Results: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. Conclusion: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

Symptoms of Depression in Patients with Chemosensory Disorders

Chemosenses are frequently reported in patients with chemosensory impairment. The present investigation intends to clarify whether there are differential pacts on symptoms of depression between the types (smell dysfunction, taste dysfunction, and combination smell and taste dysfunction), severe- ity, length or source of dysfunction. At the same time, diminished olfaction input and taste appear to have a detrimental influence on emotional dysfunction aggravation. In patients with mixed olfactory or gustatory dysfunction in clinical practice, early management should be considered for depressure symptoms. The current study sought to compare depressive symptoms in patients with mixed olfactory/gustatory dysfunction, purely olfactory disorder, and gustatory disorder, as well as to investigate the relationships between chemosensory function and depressive symptoms in various groups.

Self-Reported Symptom Study of COVID-19 Chemosensory Dysfunction in Malaysia

Alterations in the three chemosensory modalities – smell, taste, and chemesthesis – have been implicated in Coronavirus Disease 2019 (COVID-19), yet emerging data suggest a wide geographic and ethnic variation in the prevalence of these symptoms. Studies on chemosensory disorders in COVID-19 have predominantly focused on Caucasian populations whereas Asians remain understudied. We conducted a nationwide, multicentre cross-sectional study using an online questionnaire on a cohort of RT-PCR-confirmed adult COVID-19 patients in Malaysia between 6 June to 30 November 2020. The aim of our study was to investigate their presenting symptoms and assess their chemosensory function using self-ratings of perceived smell, taste, chemesthesis, and nasal blockage. In this cohort of 498 patients, 41.4% reported smell and/or taste loss when diagnosed with COVID-19, which was the commonest symptom. Blocked nose, loss of appetite, and gastrointestinal disturbances were independent predictors of smell and/or taste loss on multivariate analysis. Self-ratings of chemosensory function revealed a reduction in smell, taste, and chemesthesis across the entire cohort of patients that was more profound among those reporting smell and/or taste loss as their presenting symptom. Perceived nasal obstruction accounted for only a small proportion of changes in smell and taste, but not for chemesthesis, supporting viral disruption of sensorineural mechanisms as the dominant aetiology of chemosensory dysfunction. Our study suggests that chemosensory dysfunction in COVID-19 is more widespread than previously reported among Asians and may be related to the infectivity of viral strains. Study Registration: NMRR-20-934-54803 and NCT04390165

Self-Reported Symptom Study of COVID-19 Chemosensory Dysfunction in Malaysia

Alterations in the three chemosensory modalities – smell, taste, and chemesthesis – have been implicated in Coronavirus Disease 2019 (COVID-19), yet emerging data suggest a wide geographic and ethnic variation in the prevalence of these symptoms. Studies on chemosensory disorders in COVID-19 have predominantly focused on Caucasian populations whereas Asians remain understudied. We conducted a nationwide, multicentre cross-sectional study using an online questionnaire on a cohort of RT-PCR-confirmed adult COVID-19 patients in Malaysia between 6 June to 30 November 2020. The aim of our study was to investigate their presenting symptoms and assess their chemosensory function using self-ratings of perceived smell, taste, chemesthesis, and nasal blockage. In this cohort of 498 patients, 41.4% reported smell and/or taste loss when diagnosed with COVID-19, which was the commonest symptom. Blocked nose, loss of appetite, and gastrointestinal disturbances were independent predictors of smell and/or taste loss on multivariate analysis. Self-ratings of chemosensory function revealed a reduction in smell, taste, and chemesthesis across the entire cohort of patients that was more profound among those reporting smell and/or taste loss as their presenting symptom. Perceived nasal obstruction accounted for only a small proportion of changes in smell and taste, but not for chemesthesis, supporting viral disruption of sensorineural mechanisms as the dominant aetiology of chemosensory dysfunction. Our study suggests that chemosensory dysfunction in COVID-19 may be widespread and more common than previously thought among Asians, and manifest as an early symptom of SARS-CoV-2 infection. This has important implications for our understanding of the infectivity of viral strains, diagnosis, and management of this pandemic. Study Registration: NMRR-20-934-54803 and NCT04390165

Impact of Routine Endoscopic Skull Base Surgery on Subjective Olfaction and Gustation Outcomes

BACKGROUND As endoscopic endonasal skull base surgery (EESBS) for sellar pathology has become routine, there is increasing awareness of quality-of-life (QOL) outcomes related to this approach. Similarly, there is a growing interest in postoperative chemosensory function, with notable emphasis on olfaction and the corresponding psychosocial implications of olfactory dysfunction. Meanwhile, there has been minimal direct investigation into gustatory outcomes, and the association between these 2 chemosensory functions remains poorly understood. OBJECTIVE To investigate patient-reported chemosensory function and rhinologic-specific QOL following EESBS for routine sellar pathologies. METHODS Comprehensive clinical characteristics and sinonasal QOL assessments, measured using Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), were collected from 46 patients undergoing EESBS for sellar pathology. RESULTS Forty-six patients were included: 65.2% female, average age 52.8 yr (range: 27-89). The most common pathology was nonfunctioning pituitary adenoma (n = 28). Preoperative ASK Nasal-12 scores (mean = 0.81) demonstrated postoperative worsening at 2 wk (mean = 2.52, P < .0001) and 1 mo (mean = 1.33, P = .0031), with no difference at 3 mo postoperatively (mean = 0.89, P = .92). Meanwhile, there was significant worsening of preoperative subjective smell (mean = 0.62) and taste function (mean = 0.42) at 2 wk (mean = 3.48, P < .0001; mean = 2.69, P < .0001) and 1 mo (mean = 2.40, P < .0001; mean = 2.03, P < .0001) postoperatively, which persisted at approximately 3 mo postoperatively (mean = 1.26, P = .04; mean = 1.15, P = .0059). CONCLUSION Patients undergoing EESBS for sellar pathologies experience anticipated, temporary disruptions in sinonasal QOL but may have longer lasting perturbations in subjective olfaction and gustation. Given the increasing use of the endoscopic endonasal corridor, further investigation in postoperative chemosensory function is essential.

The course of subjective and objective chemosensory dysfunction in hospitalized patients with COVID-19: a 6-month follow-up

Purpose It has been established that the infection with SARS-CoV-2 may cause an impairment of chemosensory function. However, there is little data on the long-term effects of SARS-CoV-2 infection on chemosensory function. Methods Twenty three SARS-CoV-2-positive patients diagnosed in spring 2020 with subjective hyposmia (out of 57 positive patients, 40.3%) were compared to SARS-CoV-2-positive patients without hyposmia (n = 19) and SARS-CoV-2-negative patients (n = 14). Chemosensory function was assessed by the Brief Smell Identification Test (BSIT), Taste Strips (TS), Visual Analogue Scales (VAS), and the SNOT-22. The initial cohort with hyposmia were also examined at 8 weeks and 6 months after initial examination. Results There were no differences between the SARS-CoV-2-positive cohort without hyposmia and negative controls in terms of BSIT (8.5 ± 2.6 vs. 10.2 ± 1.8), TS (3.4 ± 0.6 vs. 3.9 ± 0.3) or VAS (2.1 ± 1.3 vs. 1.1 ± 0.5); yet the SNOT-22 was significantly elevated (27.7 ± 11.2 vs. 16.4 ± 10.8). The SARS-CoV-2-positive group with hyposmia performed significantly poorer in BSIT (4.0 ± 1.7 vs. 8.5 ± 2.6/10.2 ± 1.8), TS (2.6 ± 1.3 vs. 3.4 ± 0.6/3.9 ± 0.3), and VAS (7.9 ± 2.2 vs. 2.1 ± 1.3/1.1 ± 0.5) compared to both control groups. At week 8 and month 6 control, six and five patients, respectively, still suffered from subjectively and objectively impaired chemosensory function. The other patients had recovered in both respects. Conclusion SARS-CoV-2 patients with subjectively impaired chemosensory function regularly perform poorly in objective measurements. About 70% of patients suffering from olfactory dysfunction in SARS-CoV-2 quickly recover—the rest still suffers from considerable impairment 6 months after infection.

Chemosensory dysfunction in Cushing’s syndrome

Purpose Cushing’s syndrome (CS) can lead to structural changes in the brain and cognitive impairment, but chemosensory function has not been investigated yet. The aim was to analyze sense of smell and taste in patients with CS and explore the effect of therapy. Methods The study cohort comprised 20 patients with florid CS treated between 2018 and 2020 in the outpatient clinic of the LMU Munich. We compared these 20 patients with CS to 40 healthy subjects matched for age, sex, and smoking status. Patients’ sense of smell and taste was examined at diagnosis and 3 months after successful therapeutic surgery leading to clinical and biochemical remission. Odor threshold, discrimination, and identification were measured with “Sniffin’ Sticks”, taste was measured with “Taste Strips”. Perceived sense of smell and taste was retrieved via a questionnaire. Results Patients with florid CS had significantly reduced smell (total smell score 30.3 vs. 34.4, p < 0.0005) and taste scores (9.5 vs. 12.0, p < 0.0005) compared to controls and significantly more frequently hyposmia (55 vs. 2.5%, p < 0.0005), hypogeusia (40 vs. 0%, p < 0.0005), and self-reported chemosensory impairment (60 vs. 0%, p < 0.0005). Three months after successful surgery, CS patients showed significant improvement of odor threshold (8.1 vs. 7.0, p < 0.0005), odor discrimination (12.0 vs. 11.0, p = 0.003), total smell score (33.4 vs. 30.3, p < 0.0005), and taste (11.5 vs. 9.5, p = 0.003). Conclusions Chemosensory dysfunction is a novel and clinically relevant feature of CS.