Chemosensory assessment and impact on quality of life in neurosensorial cluster of the post COVID 19 syndrome.

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training's outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment.

High prevalence of long-term olfactory disorders in healthcare workers after COVID-19: A case-control study.

BACKGROUND: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing. METHODS: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group. RESULTS: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia. CONCLUSIONS: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.

Can Multisensory Olfactory Training Improve Olfactory Dysfunction Caused by COVID-19?

Approximately 30-60% of people suffer from olfactory dysfunction (OD) such as hyposmia or anosmia after being diagnosed with COVID-19; 15-20% of these cases last beyond resolution of the acute phase. Previous studies have shown that olfactory training can be beneficial for patients affected by OD caused by viral infections of the upper respiratory tract. The aim of the study is to evaluate whether a multisensory olfactory training involving simultaneously tasting and seeing congruent stimuli is more effective than the classical olfactory training. We recruited 68 participants with persistent OD for two months or more after COVID-19 infection; they were divided into three groups. One group received olfactory training which involved smelling four odorants (strawberry, cheese, coffee, lemon; classical olfactory training). The other group received the same olfactory stimuli but presented retronasally (i.e., as droplets on their tongue); while simultaneous and congruent gustatory (i.e., sweet, salty, bitter, sour) and visual (corresponding images) stimuli were presented (multisensory olfactory training). The third group received odorless propylene glycol in four bottles (control group). Training was carried out twice daily for 12 weeks. We assessed olfactory function and olfactory specific quality of life before and after the intervention. Both intervention groups showed a similar significant improvement of olfactory function, although there was no difference in the assessment of quality of life. Both multisensory and classical training can be beneficial for OD following a viral infection; however, only the classical olfactory training paradigm leads to an improvement that was significantly stronger than the control group.

Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2.

Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7 d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1+ cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2',3'-cyclic-nucleotide 3'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue.

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

[Features of olfactory impairment connected with trigeminal nerve system]. / Osobennosti narusheniya obonyaniya v aspekte sistemy troinichnogo nerva.

Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Assessment of olfactory recovery after COVID-19: cross-sectional study.

OBJECTIVE: This study aimed to evaluate recovery patterns of olfactory dysfunction among recovered COVID-19 patients, both subjective and objective, and correlate this recovery to the severity of the disease. METHODS: The study recruited 200 patients and assigned them to two equal groups, one of them was a control group. The olfactory function of the study group was assessed via subjective and objective methods at baseline and then monthly for three months, with changes in smell function reported at each visit. These patients underwent chemosensory testing using the Sniffin' Sticks test and completed the validated Arabic version of the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Olfactory dysfunction occurred on the first day of COVID-19 symptoms in 37% of participants. Subjective reports suggested smell recovery in 55% after 3 months, but Sniffin' Sticks showed only 1% with normal function, indicating persistent deficits in others. This study revealed smell recovery for 93% of participants (median 14 days), with most (58%) recovering within 2 weeks. No significant links were found between demographics, COVID-smell loss timing, and recovery speed. CONCLUSION: Three months after COVID-19, many patients perceive smell recovery, but objective tests reveal shockingly high rates of persistent dysfunction. Further follow-up with objective tests is vital to assess the true burden and potential long-term effects of smell loss.

Potential convergence of olfactory dysfunction in Parkinson's disease and COVID-19: The role of neuroinflammation.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.

Using SCENTinel® to predict SARS-CoV-2 infection: insights from a community sample during dominance of Delta and Omicron variants.

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

The effect of smell training on COVID-19 induced smell loss.

OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.

Taste loss in COVID-19 â€" psychophysical evidence supporting a low prevalence.

Much - possibly even too much - has been published about chemosensory dysfunction as a consequence of COVID-19. Studies have reported prevalence of taste loss in up to 89.9%, which is in a similar range as COVID-19 related smell loss. However, most of these publications rely solely on patients' self-reports. Only few studies used validated psychophysical tests to specifically address olfaction and gustation. Especially for gustation, it is evident that subjective reporting does not correlate well with more objective psychophysical findings, often leading to an overestimation of subjectively impaired taste.

Stellate ganglion block for treating post-COVID-19 parosmia.

BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.

Therapeutic Efficacy of Nasal Corticosteroids in COVID-19-Related Olfactory Dysfunction: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.

Comparison of the incidence of smell and taste disorders between influenza and COVID-19.

OBJECTIVE: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX research network. METHODS: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. RESULTS: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. CONCLUSIONS: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.

Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study.

BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group. METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin'Sticks test (Delta, Omicron and control groups). RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls. CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.

Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence.

Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID". Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2. Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021. Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.