Postviral Olfactory Dysfunction Research Articles

Determinants of long-lasting postviral COVID-19 and non-COVID-19 olfactory Dysfunction: The sanctuary theory

Since the onset of the Coronavirus disease 2019 (COVID-19) pandemic, the long-lasting postviral olfactory dysfunction (POD) became a prevalent symptom in Western country populations. However, the pathophysiology of long-lasting POD remains poorly understood. The effectiveness of platelet-rich plasma (PRP) injections into the olfactory clefts and recent findings from COVID-19 studies brought new elements in the understanding of the pathophysiology of COVID-19 and non-COVID-19 long-lasting POD. The present hypothesis suggests that the long-lasting POD could be related to a long-lasting silent chronic inflammation in the neuroepithelium due to the persistence of virus antigen into stem cells. The immune response could limit the regenerative and recovery processes, making the olfactory region an incomplete immune sanctuary for some viruses according to some specific pathophysiological phenomena (syncytia formation).

Human olfactory neurosphere-derived cells: A unified tool for neurological disease modelling and neurotherapeutic applications.

As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.

Differential connectivity of the posterior piriform cortex in Parkinson’s disease and postviral olfactory dysfunction: an fMRI study

Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson’s disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.

Alcohol Sniff Test (AST): An Important Tool for Screening Post-Viral Olfactory Loss in Acute Flu-Like Dysfunction.

Olfactory disorders have a significant impact on patients' quality of life but are often underestimated in clinical practice. Upper respiratory tract infections (URTIs) are a common cause of olfactory loss. While most cases of olfactory loss due to URTIs are conductive and reversible, post-viral olfactory dysfunction (PVOD) persists despite symptom improvement. PVOD is attributed to damage to the olfactory epithelium and nerves or central olfactory pathway lesions. The Alcohol Sniff Test (AST) has been proposed as a tool to assess olfactory function in the acute phase and aid in differentiating PVOD from conductive disorders. This study aims to evaluate the effectiveness of the AST as a predictor of post-viral olfactory loss in patients with flu-like syndrome. An observational cross-sectional study was conducted among employees with flu-like syndrome at a tertiary hospital. Three groups were formed: flu-like syndrome with conductive disorder without COVID-19 (PVOD-), flu-like syndrome with neurosensory and/or central disorder due to COVID-19 (PVOD +), and an asymptomatic control group. The Alcohol Sniff Test was performed to assess olfactory function. Statistical analysis was conducted to evaluate the AST's performance. For a cut off of 10cm, 88.57% of PVOD + patients and 60.53% of PVOD - patients showed AST alteration, respectively (p = 0.013, OR = 5.05, 95% CI [1.48-17.25]). There was a statistically significant difference in the mean distance between the PVOD + group (4.35 ± 4.1cm) and the control group (20 ± 4.33cm) (p < 0.05). This relationship was also observed between the PVOD + and PVOD- groups (9cm ± 7.5) (p < 0.05) and between the PVOD- and control groups (p < 0.05). For a cut off of 10cm, the AST showed a sensitivity of 88% and specificity of 41%, resulting in an Odds Ratio of 9.7 (95% CI 3.3-28.1) (p < 0.001) and a Positive Predictive Value of 69.4% for PVOD. PVOD, including cases associated with COVID-19, is a prevalent cause of olfactory loss. The Alcohol Sniff Test demonstrated promising results in identifying PVOD in patients with flu-like syndrome. The test's simplicity and accessibility make it a valuable tool for early screening and identifying individuals who may benefit from prompt treatment. The Alcohol Sniff Test (AST) shows potential as an effective tool for screening post-viral olfactory loss in patients with flu-like syndrome. It can aid in early identification of PVOD cases and facilitate timely interventions to reduce the likelihood of persistent hyposmia.

Sequels of COVID-19: An integrative literature review

The strong affinity between the Spike protein of the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 receptor is postulated as one of the main reasons for the high viral transmission rate, leading the WHO to declare COVID-19 as a Public Health Emergency of International Concern and to adopt measures to contain viral spread. Moreover, due to the virus’s pathophysiological mechanism, non-specific symptoms, atypical progression, especially in the elderly and immunocompromised, and a faster and more lethal progression are observed. Additionally, as knowledge about the natural history of the virus infection has advanced, persistent symptoms and/or sequelae causing organic dysfunctions and negatively impacting patients’ quality of life have been noted. In light of this, the objective of this article was to present an integrative review of the main sequels of COVID-19 in the years 2021 and 2022. To achieve this, full articles were searched in the Scientific Electronic Library Online, Biblioteca Virtual em Saúde, and PubMed research databases, in both Portuguese and English languages, using the PRISMA methodology (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), resulting in the selection of 14 articles. Among the results, the following stand out: the pathogenesis of persistent COVID-19 is based on the theory of immune phenomena secondary to infection, abnormal immune response, and the presence of the virus in immunologically privileged sites; prevalent complications include fatigue, dyspnea, subjective cognitive impairment, neurological sequelae, central nervous system inflammatory diseases, and post-viral olfactory dysfunction; evidence of a causal relationship between COVID-19 and subacute thyroiditis was presented; a higher number of complications and hospitalizations were demonstrated in vitamin D-deficient patients; as well as the presence of neuropsychiatric symptoms in the healthcare professional population. In conclusion, a scarcity of studies directly addressing COVID-19 sequelae was noted, highlighting the need for further research to create more specific diagnostic protocols.

Olfactory mucosa steroid injection in treatment of post-COVID-19 olfactory dysfunction: a randomized control trial

BackgroundOlfactory dysfunction can be a troublesome condition affecting the quality of life of the patient. Post-viral olfactory dysfunction is the most common cause attributing to up to 40% of anosmia. COVID-19 infection commonly causes anosmia in 30–66% of patients. The long-term effect of post-COVID olfactory dysfunction is reported to be increasing in incidence. Steroids are usually used in the treatment of olfactory dysfunction and most commonly used locally in the form of nasal steroid sprays, rinses, or drops. Oral systemic steroids are sometimes used; however, they have several known side effects. Other treatments experimented include giving vitamins, minerals, antioxidants, antivirals, and monoclonal antibodies, in addition to olfactory training, counseling, and acupuncture. In this study, the effect of intranasal steroid injection is studied in post-COVID olfactory dysfunction.ResultsForty patients with olfactory dysfunction post-COVID-19 for more than 3 months were randomly divided into 2 groups. Group A patients received 8 doses of dexamethasone over 2 months (twice weekly) injected near the olfactory mucosa in the nasal septum and middle turbinate, compared to group B who received saline injected in the same way as placebo. Numerically, nasal injection of corticosteroids in group A showed more subjective improvement using the questionnaire of olfactory disorders-negative statement QOD-NS than the control patients in group B but this improvement was statistically insignificant.ConclusionThe use of intranasal corticosteroids injection should be considered in the treatment of post-COVID anosmia.

Heterogeneous Damage to the Olfactory Epithelium in Patients with Post-Viral Olfactory Dysfunction.

Post-viral olfactory dysfunction (PVOD) is a neurogenic disorder caused by a common cold virus. Based on the homology of deduced amino acid sequences, olfactory sensory neurons (OSNs) in both mice and humans express either class I or class II odorant receptor genes encoding class I and class II OSNs. The purpose of this study was to determine whether OSN damage in PVOD occurs uniformly in both neuron types. The characteristics of PVOD patients were compared with those of patients with chronic rhinosinusitis (CRS) or post-traumatic olfactory dysfunction (PTOD). Briefly, subjects underwent orthonasal olfaction tests using five different odors (T&T odors) and a retronasal olfaction test using a single odor (IVO odor). The regions in the mouse olfactory bulb (OB) activated by the T&T and the IVO odors were also examined. Multivariate analysis of 307 cases of olfactory dysfunction (PVOD, 118 cases; CRS, 161 cases; and PTOD, 28 cases) revealed that a combination of responses to the IVO odor, but not to the T&T odors, is characteristic of PVOD, with high specificity (p < 0.001). Imaging analysis of GCaMP3 mice showed that the IVO odor selectively activated the OB region in which the axons of class I OSNs converged, whereas the T&T odors broadly activated the OB region in which axons of class I and class II OSNs converged. A response to T&T odors, but not IVO odor, in PVOD suggests that class I OSNs are injured preferentially, and that OSN damage in PVOD may occur heterogeneously in a neuron-type-dependent manner.

Olfactory Dysfunction following COVID-19 and the Potential Benefits of Olfactory Training.

This is a cross-sectional study conducted among adults aged 18-60 living in Alahssa, Saudi Arabia. An online questionnaire containing an informed consent form and a survey to collect demographic data, vaccination status, level of loss of smell and taste, and the level of awareness about olfactory training (OT) was distributed among all participants who agreed to participate in this study. The study included 524 participants and presented their baseline characteristics, including age, gender, COVID-19 infection status, and complaints. Most patients were female (66.0%), and 46.2% had previously been infected with COVID-19. About 54.8% of participants reported chemosensory dysfunction, while 286 had olfactory dysfunction. Of those, 29.8% had anosmia, 16.8% had hyposmia, and 8.0% had parosmia. Results suggest that being fully or partially vaccinated may offer some protection against olfactory dysfunction compared to being unvaccinated. Adherence to olfactory training was associated with improvement in the sense of smell. The study highlights the importance of awareness and adherence to olfactory training, which may improve the sense of smell in individuals with chemosensory dysfunction. The findings of this study can inform public health policies and interventions aimed at reducing the burden of olfactory dysfunction associated with COVID-19 vaccination.

Clinical characteristics and associated factors of qualitative olfactory dysfunction.

Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD. Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia. Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia. Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.

Assessment of factors influencing the olfactory bulb volume in patients with post-viral olfactory dysfunction.

To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. Male patients with PVOD had a larger OB volume (β = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (β = -0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (β = -0.476, P < 0.05). The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD.

Bacterial communities in the nasal passage of postviral olfactory dysfunction patients.

Bacterial composition is uniform in the sinuses of postviral olfactory dysfunction patients. Significant reduction of genus Corynebacterium in PVOD patients compared to controls.

Zika virus leads to olfactory disorders in mice by targeting olfactory ensheathing cells.

Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown. We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa. We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication. Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients. Stated in the acknowledgment.

The Effect of Traditional Chinese Medicine on Postviral Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

The aim of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postviral olfactory dysfunction (PVOD). PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical (CBM) Database, and Wanfang Database were electronically searched from their inception to July 25, 2022. Two authors independently performed study selection, data extraction, and quality assessment to ensure systematic quality evaluation. Randomized controlled trials (RCTs) comparing TCM with olfactory training and/or drug therapy (OTDT) were included. The outcomes were the effective rate, QOD-P, TDI score, UPSIT score, and adverse effects. Cochrane RoB was the guideline used to evaluate the methodological quality of the included trials. RevMan 5.3 software was used for statistical analysis. A total of 6 RCTs involving 467 patients with PVOD were selected. Compared with OTDT, TCM plus OTDT decreased QOD-P (MD = -1.73, 95% CI (-2.40, -1.06), P < 0.0001) but did not increase the effective rate (T&T) (RR = 1.28, 95% CI (0.86, 1.90), P=0.22, I 2 = 61%). Compared with no treatment, TCM seemed to increase the treatment success rate (UPSIT) (RR = 3.17, 95% CI (1.78, 5.65), P < 0.0001, I 2 = 0%), but there was no statistically significant difference in improving the UPSIT score (MD = 3.44, 95% CI (-1.36, 8.24), P=0.16). Compared with drug therapy, TCM plus drug therapy appeared to increase the effective rate (ΔVAS) (RR = 2.36, 95% CI (1.41, 3.94), I 2 = 0%), but there was no statistically significant difference in improving the TDI score (MD = 2.10, 95% CI (-1.99, 6.19), P=0.31). No significant differences in adverse reactions were reported between TCM and OTDT. TCM may be an effective treatment for PVOD. With a lack of high-quality RCTs, further large-scale and high-quality RCTs are still warranted.

Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study

Introduction: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. Methods: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. Results: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. Conclusions: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.

Assessment of postviral qualitative olfactory dysfunction using the short SSParoT in patients with and without parosmia.

PurposeTo examine if the short formed Sniffin Sticks Parosmia Test (SSParoT), a test for parosmia can distinguish cases with parosmia from cases without parosmia.MethodsIn this study, 63 patients with postviral olfactory dysfunction were investigated including both COVID and non-COVID cases. The age, symptom duration, degree of parosmia/phantosmia was collected. For olfactory function, the Sniffin Sticks olfactory score was obtained including scores for odor threshold, discrimination and identification. For assessment of parosmic changes, the short SSParoT was adopted and both hedonic range (HedRang) and direction (HedDir) was calculated.ResultsThe mean HedRang of patients with parosmia (2.35, standard deviation, SD = 1.40) and without parosmia (2.78, SD = 1.09) was smaller than that in controls (4.5, SD = 2.15). However, the mean HedDir of both parosmia (− 0.32, SD = 0.98) and non-parosmia patients (0.04, SD = 1.07) was similar to controls (− 0.1, SD = 1.55). When considering that the 10th percentile of the distribution of SSParoT score should distinguish between patients with and without parosmia, the sensitivity of the HedRang was 29% and specificity was 67%. For HedDir, the sensitivity was 6% and specificity was 100%. Only the odor identification score (r = 0.34, p = 0.01) discriminated parosmia and non-parosmia while other measures including HedRang and HedDir did not.ConclusionThe present study showed that the short SSParoT score could not distinguish patients with parosmia from patients without parosmia. Although the SSParoT represents an innovative approach to assess parosmia, and could be useful in the tracking of parosmic changes, the development of measures to diagnose parosmia in an objective way remains a challenge.

Safety of High-Dose Nasal Theophylline Irrigation in the Treatment of Postviral Olfactory Dysfunction: A Dose-Escalation Study

Safety of High-Dose Nasal Theophylline Irrigation in the Treatment of Postviral Olfactory Dysfunction: A Dose-Escalation Study

Efficacy and Safety of Saline Nasal Irrigation Plus Theophylline for Treatment of COVID-19–Related Olfactory Dysfunction

Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic. To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD. This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021. Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks. The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions. A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline. This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully. ClinicalTrials.gov Identifier: NCT04789499.

Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health.

Decreased smell function is related to brain health, future mortality, and quality of life. Most people inflicted with the SARS-CoV-2 virus evidence some measurable smell dysfunction during its acute phase, although many are unaware of the loss. Long-term deficits occur in up to 30% of COVID-19 cases, although total anosmia is relatively rare. This review explores what is presently known about the nature and pathophysiology of olfactory dysfunction due to the SARS-CoV-2 virus, including reversible inflammation within the olfactory cleft, downregulation of olfactory receptor proteins, and long-lasting peripheral and central damage to olfactory structures. It also addresses the question as to whether long-term smell loss might increase the likelihood of future development of cognitive and neurological deficits.

Assessment of olfactory fluctuations in a clinical context

PurposeThe aim of the study was to investigate whether olfactory fluctuations (OF) are pronounced in patients with sinonasal olfactory dysfunction (OD).MethodsThe retrospective investigation included patients aged 18 years or older, who consulted a tertiary referral center for olfactory loss. Patients with normal smell function were excluded. Patients answered a structured questionnaire about their olfactory symptoms, with specific questions related to the presence of OF and its average frequency, amplitude, duration, time since most recent OF, and associated symptoms of self-reported OF. Patients also underwent clinical evaluation including a structured medical history and physical examination including nasal endoscopy. In addition, we assessed orthonasal olfactory function using Sniffin’ Sticks, and gustatory function using “taste sprays”.ResultsParticipants included 131 men and 205 women (n = 336), aged 18 to 86 years (mean 50, SD 16). Patient-reported fluctuations occurred most frequently in sinonasal (38%), idiopathic (29%), and postviral (29%) OD. Amplitude of OF was highest in postviral OD (p = 0.009). Average frequency, duration, and the time since the most recent fluctuation were not significantly different between groups (all p’s > 0.42). Odor discrimination (p = 0.002) and identification (p = 0.017) scores were higher among those individuals with OF.ConclusionAmplitude of OF may help distinguish postviral from other causes of OD, especially in patients presenting with equivocal symptoms of sinonasal disease.

Chemical Constituents of Essential Oils Used in Olfactory Training: Focus on COVID-19 Induced Olfactory Dysfunction

The recent increase in the number of patients with post-viral olfactory dysfunction (PVOD) following the outbreak of COVID-19 has raised the general interest in and concern about olfactory dysfunction. At present, no clear method of treatment for PVOD has been established. Currently the most well-known method to improve the symptoms of olfactory dysfunction is “olfactory training” using essential oils. The essential oils used in olfactory training typically include rose, lemon, clove, and eucalyptus, which were selected based on the odor prism hypothesis proposed by Hans Henning in 1916. He classified odors based on six primary categories or dimensions and suggested that any olfactory stimulus fits into his smell prism, a three-dimensional space. The term “olfactory training” has been used based on the concept of training olfactory sensory neurons to relearn and distinguish olfactory stimuli. However, other mechanisms might contribute to how olfactory training can improve the recovery of the olfactory sense. Possibly, the essential oils contain chemical constituents with bioactive properties that facilitate the recovery of the olfactory sense by suppressing inflammation and enhancing regeneration. In this review, we summarize the chemical constituents of the essential oils of rose, lemon, clove, and eucalyptus and raise the possibility that the chemical constituents with bioactive properties are involved in improving the symptoms of olfactory dysfunction. We also propose that other essential oils that contain chemical constituents with anti-inflammatory effects and have binding affinity with SARS-CoV-2 can be new candidates to test their efficiencies in facilitating the recovery.