Persistent Olfactory Dysfunction Research Articles

Short-term efficacy of platelet-rich plasma in the treatment of persistent olfactory dysfunction: systematic review and meta-analysis.

To assess the short-term effects of topical platelet-rich plasma (PRP) injection on persistent refractory olfactory dysfunction. A comprehensive literature search of the PubMed, SCOPUS, EMBASE, Web of Science, Google Scholar, and Cochrane databases was conducted for articles up to November 2023. The search focused on studies that compared the amelioration of olfactory dysfunction between a topical PRP treatment cohort and a control group (receiving either placebo or no treatment), along with pre- and post-treatment comparisons. Subgroup analysis of the evaluation of olfactory function was also performed. The improvement in olfactory scores 1-3months post-treatment (standardized mean difference = 1.5354 [95% confidence interval: 0.7992; 2.2716], I2 = 83.8%) was greater in the treatment group than in the control group. In the treatment group, PRP increased the threshold, discrimination, and identification (TDI) score for Sniffin' Sticks by > 5.5 (minimum clinically significant difference; mean difference = 6.1789 [3.9788; 8.3789], I2 = 0.0%), indicating clinically significant improvement based on verified examinations. The rate of significant improvement among patients was 0.6683 [0.5833; 0.7436] after treatment. All TDI subdomains were significantly and similarly improved after treatment. This meta-analysis suggests that injection of PRP into the olfactory fissure or surrounding mucosal areas is an effective treatment for persistent refractory olfactory dysfunction in the short term.

Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19.

Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the "Sniffin' Sticks" test, measuring threshold, discrimination and identification scores before and after treatment. Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. DFM-IRB00012367-23-10-001.

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.

COVID-19 olfactory dysfunction: associations between coping, quality of life, and mental health.

Persistent olfactory dysfunction (OD) is a common symptom following SARS-CoV-2 infection that can greatly impact quality of life (QoL). Because coping strategies have been shown to moderate the effect of disease symptoms on functional and affective outcomes, this study aims to determine whether specific coping strategies are associated with and moderate QoL outcomes. Participants with prior SARS-CoV-2 infection underwent psychophysical olfactory testing with Sniffin' Sticks and completed questionnaires to elicit subjective olfactory function, coping strategies, olfactory-specific QoL, general QoL, and mental health. There were 93 participants included in the study. Olfactory specific QoL scores were significantly worse among individuals with subjective and psychophysically measured OD compared to those with subjective and psychophysically confirmed normosmia. Olfactory-specific QoL, general QoL, and anxiety symptom scores were positively correlated with avoidant and disengagement coping among individuals with subjective and psychophysically measured OD. Depression symptom scores were positively correlated with avoidant and disengagement coping and negatively correlated with approach and engagement coping. There were no significant moderating effects on the association between olfactory performance and QoL or mental health screening assessment. Approach and engagement coping mechanisms are associated with improved depression, whereas avoidant and disengagement coping tracks with worse QoL and mental health screening assessment, offering an opportunity to counsel patients accordingly.

Palmitoylethanolamide and Luteolin for Postinfectious Olfactory Disorders: How Clinically Meaningful Is Its Effect?

The prevalence of post-viral olfactory dysfunction has increased significantly during the COVID-19 pandemic, posing a major challenge for patients and practitioners. While olfactory training (OT) is a common approach to therapy, there has been increasing interest in supplementing therapy with a combination of palmitoylethanolamide (PEA) and luteolin (LUT), which are known for their anti-inflammatory properties. In this study, their efficacy in the treatment of patients with olfactory loss following upper respiratory tract infections, mainly COVID-19, was investigated in an outpatient clinic. Fifty patients with persistent olfactory dysfunction were randomized to two groups: one receiving OT and PEA-LUT, the other OT alone. Olfactory function was evaluated before and after treatment. The study group showed significant improvements in odor discrimination and overall olfactory function (TDI score) after treatment with PEA-LUT and OT, while the control group did not. However, when clinically meaningful improvements were considered, there was no significant difference between the groups. The present study suggests that while PEA-LUT may have the potential to improve olfactory function in post-viral dysfunction, the additional benefit over OT alone may be limited. These results contrast with some previous studies.

Effect of Olfactory Rehabilitation on the Recovery of Post-Coronavirus Disease Olfactory Dysfunction: A Randomized Controlled Trial.

Introduction Persistent olfactory dysfunction was seen in many patients upon coronavirus disease 2019 (COVID-19) infection recovery. However, research on its management was very limited, especially among the Southeast Asian population. Objectives We aim to investigate the role of olfactory rehabilitation and topical corticosteroids among post-COVID-19 olfactory dysfunction patients in Malaysia, and at the same timeto determine factors leading to olfactory recovery post-COVID-19 infection. Methods Adult Malaysians with persistent olfactory dysfunction one month post-COVID-19 recovery were recruited. Thirty-one patients were randomly assigned into three groups with 10 patients being given olfactory training (Group 1), another 10 being given mometasone furoate nasal spray/olfactory training (Group 2), and 11 patients being assigned to the control group (Group 3). All groups were followed up for an average duration of six months. Olfactory function was evaluated by Top International Biotech Smell Identification Test (TIBSIT) scores and Olfactory Disorder Questionnaire (eODQ) prior to randomization, at three and six months after recruitment. Results The baseline characteristics of patients were similar in all groups. Generally, patients of all three groups showed a statistically significant improvement in the TIBSIT scores after six months. The TIBSIT scores for Group 2 were statistically significantly higher than the control at three months but not at six months. As for Group 1, no statistically significant differences in TIBSIT scores at both three and six months were noted when compared to control. Statistically significant improvements were seen in the eODQ scores in all three groups. Conclusion No superiority of intervention for post-COVID-19 olfactory dysfunction was seen compared to control.

Recovery rates and long‐term olfactory dysfunction following COVID‐19 infection

AbstractObjectivesOlfactory dysfunction is one of the most recognized symptoms of COVID‐19, significantly impacting quality of life, particularly in cases where recovery is prolonged. This review aims to explore patterns of olfactory recovery post‐COVID‐19 infection, with particular focus on delayed recovery.Data SourcesPublished literature in the English language, including senior author's own work, online and social media platforms, and patients' anecdotal reports.MethodA comprehensive review of the literature was undertaken by the authors with guidance from the senior author with expertise in the field of olfaction.ResultsBased on self‐report, an estimated 95% of patients recover their olfactory function within 6 months post‐COVID‐19 infection. However, psychophysical testing detects higher rates of persistent olfactory dysfunction. Recovery has been found to continue for at least 2 years postinfection; negative prognostic indicators include severe olfactory loss in the acute phase, female sex, and older age. Variability in quantitative and qualitative disturbance in prolonged cases likely reflects both peripheral and central pathophysiological mechanisms. Limitations of many of the reviewed studies reflect lack of psychophysical testing and baseline olfactory assessment.ConclusionsPost‐COVID‐19 olfactory dysfunction remains a significant health and psychosocial burden. Emerging evidence is improving awareness and knowledge among clinicians to better support patients through their olfactory rehabilitation, with hope of recovery after several months or years. Further research is needed to better understand the underlying pathogenesis of delayed recovery, identify at risk individuals earlier in the disease course, and develop therapeutic targets.

Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics

PurposeAlthough COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.MethodsAfter screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin’ Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.ResultsThe umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.ConclusionsumPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

A Comprehensive Review of COVID-19-Related Olfactory Deficiency: Unraveling Associations with Neurocognitive Disorders and Magnetic Resonance Imaging Findings.

Olfactory dysfunction (OD) is one of the most common symptoms in COVID-19 patients and can impact patients' lives significantly. The aim of this review was to investigate the multifaceted impact of COVID-19 on the olfactory system and to provide an overview of magnetic resonance (MRI) findings and neurocognitive disorders in patients with COVID-19-related OD. Extensive searches were conducted across PubMed, Scopus, and Google Scholar until 5 December 2023. The included articles were 12 observational studies and 1 case report that assess structural changes in olfactory structures, highlighted through MRI, and 10 studies correlating the loss of smell with neurocognitive disorders or mood disorders in COVID-19 patients. MRI findings consistently indicate volumetric abnormalities, altered signal intensity of olfactory bulbs (OBs), and anomalies in the olfactory cortex among COVID-19 patients with persistent OD. The correlation between OD and neurocognitive deficits reveals associations with cognitive impairment, memory deficits, and persistent depressive symptoms. Treatment approaches, including olfactory training and pharmacological interventions, are discussed, emphasizing the need for sustained therapeutic interventions. This review points out several limitations in the current literature while exploring the intricate effects of COVID-19 on OD and its connection to cognitive deficits and mood disorders. The lack of objective olfactory measurements in some studies and potential validity issues in self-reports emphasize the need for cautious interpretation. Our research highlights the critical need for extensive studies with larger samples, proper controls, and objective measurements to deepen our understanding of COVID-19's long-term effects on neurological and olfactory dysfunctions.

Mucosal antibody response and SARS-CoV-2 shedding in patients with COVID-19 related olfactory dysfunction.

Olfactory dysfunction (OD) was one of the most common symptom of infection with the Wuhan strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and could persist for several months after symptom onset. The pathogenesis of prolonged OD remains poorly understood but probably involves sustained viral replication associated with limited mucosal immune response to the virus. This prospective study was conducted to investigate the potential relationship between nasal SARS-CoV-2 viral load and antibody levels in patients with loss of smell. One hundred and five patients were recruited 2 weeks after presenting with confirmed coronavirus disease 2019 associated OD. Based on the identification sniffing test performed at enrollment, 52 patients were still anosmic or hyposmic and 53 were normosmic. SARS-CoV-2 was detectable in nasal wash of about 50% of anosmic and normosmic patients. Higher viral load was detected in anosmic patients with lower levels of SARS-CoV-2 specific nasal immunoglobulins (Ig) IgG and IgA. This association was not observed in normosmic patients. No relationship between nasal viral load and antibodies to endemic coronaviruses was observed. SARS-CoV-2 replication in the nasal cavity may be promoted by defective mucosal antibody responses in patients with OD. Boosting mucosal immunity may limit nasal SARS-CoV-2 replication and thereby help in the control of persistent OD.

Navigating the intersection of Post-COVID olfactory dysfunction and mental Health: A biopsychosocial case study

Background: Olfactory Dysfunction (OD) post-SARS-CoV-2 infection can manifest in various forms, including qualitative impairments such as parosmia. We describe a 26-year-old woman's trajectory from anosmia following COVID-19 infection to parosmia, which evolved into severe depression. This young woman from North India began perceiving a "garbage-like" odor from food items several months after recovering from COVID-19. Her distress from this condition, exacerbated by her family's lack of understanding, led to significant dietary restrictions, weight loss, and subsequent development of an episode of severe depression linked to the distress from her persistent olfactory dysfunction. A combination of escitalopram, olanzapine, and carbamazepine was initiated alongside psychoeducation sessions for the family. Over the following months, her depressive and olfactory symptoms showed significant improvement. This case illuminates the complex relationship between sensory dysfunction and mental health post-COVID-19, emphasizing the need for an integrated biopsychosocial treatment approach and the crucial role of familial understanding and support.

Assessment of anosmia/hyposmia in post-COVID-19 patients: a cross-sectional study in an eastern province of Saudi Arabia.

A cross-sectional study that was conducted in the Department of Physiology, College of Medicine, Imam Abdulrahman bin Faisal University, Khobar, Saudi Arabia. One hundred and forty-seven participants were included in this study, and sixty of them agreed to participate in the objective testing using the Connecticut Chemosensory Clinical Research Center (CCCRC) olfaction test. There was a significant correlation between the following factors: (1) Persistence of anosmia/hyposmia and the time of onset of anosmia/hyposmia (P=0.015). (2) Persistence of anosmia/hyposmia and the duration of anosmia/hyposmia (P=0.012). (3) Duration of anosmia/hyposmia and the duration of COVID-19 symptoms (P=0.010). Interestingly, there was a significant association between the subjective participants' claim of anosmia/hyposmia and the score of their objective assessment (P=0.026). The current study demonstrated that post-COVID-19 participants with delayed onset of anosmia/hyposmia and/or longer duration of either anosmia/hyposmia or COVID-19 symptoms were prone to have persistent olfactory dysfunction. Further studies are necessary to uncover the underlying pathophysiology and management of this olfactory dysfunction in COVID-19 patients.

Functional magnetic resonance imaging in coronavirus disease 2019 induced olfactory dysfunction.

To evaluate the functional magnetic resonance imaging changes in the olfactory structures of coronavirus disease 2019 patients experiencing olfactory dysfunction. This study included patients aged 25-65 years who presented with a sudden loss of smell, confirmed coronavirus disease 2019 infection, and persistent olfactory dysfunction for a minimum of 2 months without any treatment. Irrespective of the side of brain activation, the analysis of the cumulative maximum diameter of the activation zones revealed significantly lower activation in the upper frontal lobe (p = 0.037) and basal ganglia (p = 0.023) in olfactory dysfunction patients. Irrespective of the side of activation, the analysis of the number of activation points demonstrated significantly lower activation in the upper frontal lobe (p = 0.036) and basal ganglia (p = 0.009) in olfactory dysfunction patients. Patients with coronavirus-triggered olfactory dysfunction exhibited lower activity in their basal ganglia and upper frontal lobe.

Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

Remote psychophysical testing of smell in patients with persistent olfactory dysfunction after COVID-19

Olfactory dysfunction associated with coronavirus 2 (SARS-CoV-2) infection is in most cases transient, recovering spontaneously within a few days. However, in some patients it persists for a long time, affects their everyday life and endangers their health. Hence, we focused on patients with persistent loss of smell. The aim of this study was to evaluate olfactory dysfunction using a standardized test. Due to the pandemic, olfactory testing was performed online. Smell tests (Odorized Markers Test, OMT) were sent home to the patients. Together with the smell self-testing, participants reported and assessed several parameters (age, sex, subjective assessment of smell and taste, nasal patency, etc.) in an online questionnaire. Based on the questionnaire outcomes, the results were sent to the patients along with a list of participating otolaryngologists who provided them with professional care. From March to June 2021, 1025 patients requested smell testing, of these, 824 met the inclusion criteria of this study. The duration of the olfactory dysfunction at the time of testing ranged from 1 month to 1 year. Using the OMT, impaired smell ability—anosmia or hyposmia—was confirmed in 82.6% of participants. A total of 17.4% of participants were determined to be normosmic however, more than 50% of them complained of parosmia and/or phantosmia. Our study demonstrates the relevance of psychophysical smell testing and its suitability for remote use during the pandemic. This study also revealed several correlations between prolonged olfactory dysfunction and the monitored parameters.

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

Persistent olfactory dysfunction associated with poor sleep quality and anxiety in patients with long COVID.

Poor sleep quality have been widely reported in patients with long COVID. Determining the characteristics, type, severity, and relationship of long COVID with other neurological symptoms is essential for the prognosis and management of poor sleep quality. This cross-sectional study was conducted at a public university in the eastern Amazon region of Brazil between November 2020 and October 2022. The study involved 288 patients with long COVID with self-report neurological symptoms. One hundred thirty-one patients were evaluated by using standardised protocols: Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory, Chemosensory Clinical Research Center (CCRC), and Montreal Cognitive Assessment (MoCA). This study aimed to describe the sociodemographic and clinical characteristics of patients with long COVID with poor sleep quality and their relationship with other neurological symptoms (anxiety, cognitive impairment, and olfactory disorder). Patients with poor sleep quality were mainly women (76.3%), 44.04 ± 12.73 years old, with >12 years of education (93.1%), and had monthly incomes of up to US $240.00 (54.2%). Anxiety and olfactory disorder were more common in patients with poor sleep quality. Multivariate analysis shows that the prevalence of poor sleep quality was higher in patients with anxiety, and olfactory disorder is associated with poor sleep quality. In this cohort of patients with long COVID, the prevalence of poor sleep quality was highest in the group tested by PSQI and were associated with other neurological symptoms, such as anxiety and olfactory dysfunction. A previous study indicates a significant association between poor sleep quality and psychological disorders over time. Recent studies involving neuroimaging found functional and structural changes in Long COVID patients with persistent olfactory disfunction. Poor sleep quality are integral part of complex changes related to Long COVID and should be part of patient's clinical management.

Treatment of Olfactory Disorders After SARS - CoViD 2 Virus Infection.

The benefit of a nasal corticosteroid in the treatment of persistent post-infectious smell disorders is not as clear in previous studies as is assumed for olfactory training. This study would therefore like to describe the treatment strategies using the example of a persistent olfactory dysfunction as a result of a proven infection with SARS-CoViD-2-virus. Twenty patients (average age of 33.9 ± 11.9years) with hyposmia were included in this study from December 2020 to July 2021. Every second patient received additionally a nasal corticosteroid. The two resulting randomized groups of equal size were screened with the TDI test, a 20-item taste powder test for the assessment of retronasal olfaction and otorhinolaryngological examination. The patients were asked to train twice daily using a standardized odor training kit and followed up after 2months and 3months, respectively. We documented a significant overall improvement in olfactory ability over the investigation period in both groups. While the TDI score steadily increased on average under the combination therapy, the rise under olfactory training alone was initially steeper. This short-term interaction effect over mean two months was not statistically significant. According to Cohen, however, a moderate effect (eta2 = 0.055, Cohen`s d = 0.5) can still be assumed. This effect could be explained by a possibly higher compliance at the beginning of the sole olfactory training due to the lack of further drug treatment offers. When the training intensity decreases, the recovery of the sense of smell stagnates. Adjunctive therapy ultimately outweighs this short-term benefit. The results reinforce the recommendation of early and consistent olfactory training on patients with dysosmia due to COVID-19. For continuous improvement of the sense of smell, an accompanying topical treatment seems at least to be worth consideration. The results should be optimized with larger cohorts and using new objective olfactometric methods.

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] vs34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs8.25 [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.

Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction

ObjectivesTo explore the neuropsychological profile and the integrity of the olfactory network in patients with COVID-19-related persistent olfactory dysfunction (OD). MethodsPatients with persistent COVID-19-related OD underwent olfactory assessment with Sniffin’ Sticks and neuropsychological evaluation. Additionally, both patients and a control group underwent brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI) sequences on a 3 T scanner. Morphometrical properties were evaluated in olfaction-associated regions; the rs-fMRI data were analysed using graph theory at the whole-brain level and within a standard parcellation of the olfactory functional network. All the MR-derived quantities were compared between the two groups and their correlation with clinical scores in patients were explored. ResultsWe included 23 patients (mean age 37 ± 14 years, 12 females) with persistent (mean duration 11 ± 5 months, range 2–19 months) COVID-19-related OD (mean score 23.63 ± 5.32/48, hyposmia cut-off: 30.75) and 26 sex- and age-matched healthy controls. Applying population-derived cut-off values, the two cognitive domains mainly impaired were visuospatial memory and executive functions (17 % and 13 % of patients). Brain MRI did not show gross morphological abnormalities. The lateral orbital cortex, hippocampus, and amygdala volumes exhibited a reduction trend in patients, not significant after the correction for multiple comparisons. The olfactory bulb volumes did not differ between patients and controls. Graph analysis of the functional olfactory network showed altered global and local properties in the patients’ group (n = 19, 4 excluded due to artifacts) compared to controls. Specifically, we detected a reduction in the global modularity coefficient, positively correlated with hyposmia severity, and an increase of the degree and strength of the right thalamus functional connections, negatively correlated with short-term verbal memory scores. DiscussionPatients with persistent COVID-19-related OD showed an altered olfactory network connectivity correlated with hyposmia severity and neuropsychological performance. No significant morphological alterations were found in patients compared with controls.