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In patients with chronic severe rhinosinusitis and nasal polyps, tezepelumab therapy led to greater reductions in polyp size and nasal congestion and less use of surgery and glucocorticoids than placebo.

To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 2020, using the terms anosmia or hyposmia or dysosmia or olfactory dysfunction or olfaction disorder or smell dysfunction or ageusia or hypogeusia or dysgeusia or taste dysfunction or gustatory dysfunction or neurological and COVID-19 or 2019 novel coronavirus or 2019-nCoV or SARS-CoV-2. The references of included studies were also manually screened. Only studies involving patients with diagnostic-confirmed COVID-19 infection were included. Random-effects meta-analysis was performed. Twenty-four studies with data from 8438 patients with test-confirmed COVID-19 infection from 13 countries were included. The pooled proportions of patients presenting with olfactory dysfunction and gustatory dysfunction were 41.0% (95% CI, 28.5% to 53.9%) and 38.2% (95% CI, 24.0% to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = −0.076; P=.02) and gustatory (coefficient = −0.073; P=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared with self-reports (coefficient = 2.33; P=.01). No significant moderation of the prevalence of OGDs by sex was observed. There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.

Background Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume and size of olfactory-related brain regions, such as the olfactory bulb and hippocampus, as well as changes in functional connectivity in non-surgical adults. Despite promising findings in mice, it remains unknown whether olfactory training reduces PND in surgical patients. We therefore propose a randomized clinical trial. Methods and analysis This sham-controlled assessor-blind randomized controlled trial will enroll 686 patients aged 65 and older who are scheduled for orthopedic Surgery expected to last at least 2h under general anesthesia. Participants will be randomized 1:1 to olfactory enrichment or sham treatment. Those assigned to the olfactory enrichment group will receive twice-daily 30-min sessions involving four distinct odors, beginning on 1 day before surgery and continuing for three postoperative days during hospitalization. Patients assigned to sham treatment will follow the same schedule, but with odorless substances in the scent dispenser. The primary outcome is the incidence of postoperative delirium, assessed using the 3-min diagnostic interview for CAM-defined delirium (3D-CAM) on postoperative days 1, 2, and 3. Secondary outcomes include the incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder, evaluated through cognitive function assessments using neuropsychological tests at baseline, 21 days, and 6 months after the anesthesia/surgery. Exploratory outcomes include the severity of delirium measured by the CAM-severity (CAM-S) tools, the severity of delayed neurocognitive recovery and postoperative neurocognitive disorder assessed through neuropsychological tests, evaluations of activities of daily living, plasma Tau-PT217 levels, and olfactory function. Discussion This is the first clinical trial to evaluate the efficacy of olfactory enrichment in geriatric patients undergoing orthopedic surgery, filling an important gap in the treatment evidence for PND. Trial registration The trail has been registered in ClinicalTrial.gov with the Trial Registration Number of NCT06488807. Date of registration in the primary registry: June 15, 2024. The study is anticipated to start in March 2025. The anticipated primary completion date is December 31, 2027. 

Purpose The aim of the present study was to estimate the 1 year prevalence and recovery rate of self-reported chemosensory dysfunction in a series of subjects with previous mild-to-moderate symptomatic COVID-19. Methods Prospective study based on the SNOT-22, item “sense of smell or taste” and additional outcomes. Results 268/315 patients (85.1%) completing the survey at baseline also completed the follow-up interview. The 12 months prevalence of self-reported COVID-19 associated chemosensory dysfunction was 21.3% (95% CI 16.5–26.7%) . Of the 187 patients who complained of COVID-19 associated chemosensory dysfunction at baseline, 130 (69.5%; 95% CI 62.4–76.0%) reported complete resolution of smell or taste impairment, 41 (21.9%) reported a decrease in the severity, and 16 (8.6%) reported the symptom was unchanged or worse 1 year after onset. The risk of persistence was higher for patients reporting a baseline SNOT-22 score ≥ 4 (OR = 3.32; 95% CI 1.32–8.36) as well as for those requiring ≥ 22 days for a negative swab (OR = 2.18; 95% CI 1.12–4.27). Conclusion A substantial proportion of patients with previous mild-to-moderate symptomatic COVID-19 characterized by new onset of chemosensory dysfunction still complained on altered sense of smell or taste 1 year after the onset.

The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

Introduction Smell disorders are common in the general population and occur e.g., after infections, trauma or idiopathically Treatment strategies for smell loss range from surgery, medication to olfactory training, depending on the pathology, but they are limited This study examined the effect of acupuncture on olfactory function. Methods Sixty patients with smell loss following infections of the upper respiratory tract were included in this investigation Half of the study group were randomly assigned to verum acupuncture and the other half to sham acupuncture Olfaction was measured by means of the “Sniffin’ Sticks” test battery (odour threshold, discrimination and identification). Results Compared to sham acupuncture, verum was associated with an improvement of smell function as measured by the TDI score ( p  = 0.039) The improvement was largely determined by improvement in odour discrimination, and was significantly better in patients with a shorter duration of the disorder. Conclusion The present results suggest that acupuncture is an effective supplementary treatment option for patients with olfactory loss.

Purpose Although 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. Methods After 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 (T 0 ) and 6 months (T 1 ) 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. Results The 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. Conclusions umPEALUT 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.

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. After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition with neurological symptoms. Here, the authors show symptom-specific brain microstructure alterations in these patients, providing insights into the underlying pathophysiology.

IntroductionEndoscopic sinus surgery is an effective treatment for olfactory dysfunction related to chronic rhinosinusitis (CRS). However, recent studies have shown that most patients with CRS experience a return of olfactory function to preoperative levels within months to a year after surgery. Clinically, olfactory training after sinonasal surgery has been proven beneficial for olfactory recovery. The study aims to explore the effectiveness of olfactory training in treating postoperative olfactory dysfunction in patients with CRS after surgery. Additionally, conventional olfactory training (COT) devices have the drawback of insufficient deposition rates of odourants in the olfactory cleft, leading to poor treatment outcomes. This experiment employs a modified olfactory training (MOT) device based on respiratory pressure and compares its therapeutic effects with the COT device.Methods and analysisThis will be a randomised controlled trial. The aim is to investigate the effectiveness of olfactory training in treating postoperative olfactory dysfunction in patients with CRS and to compare the effects of MOT with COT. Participants will be randomly allocated in a 1:1:1 ratio to the MOT group, the COT group and the control group for 12 months. The primary outcome will be the change in the odour threshold, odour discrimination, odour identification and the total threshold, detection and identification score after 12 months of olfactory training. The secondary outcomes will include objective olfactory cleft assessment, the volumes of grey matter, white matter and cerebrospinal fluid, the volume and shape of the olfactory bulb, and the subjective olfactory assessment.Ethics and disseminationThis study protocol has been registered with ClinicalTrials.gov and has received approval from the Peking University Third Hospital Medical Science Research Ethics Committee. The results will be published in scientific peer-reviewed journals.Trial registration numberNCT06837051.

IntroductionOlfactory dysfunction (OD) following COVID-19 affected up to 70% of patients, with more than 30% still reporting lingering symptoms a year later. Treatment is essential, as previous research has linked (postviral) OD to depression, impaired quality of life (QoL) and even heightened mortality rates.Methods and analysisWe designed a monocentric, single-blinded randomised controlled trial evaluating the efficacy of olfactory training (OT) in individuals with persisting COVID-19-associated loss of smell. Randomisation will be done in a 1:1 manner. OT will be performed using the Sniffin’ Sticks Duft Quartett over a period of 12 weeks, two times per day. The primary endpoint of this study is the change in olfactory score between baseline and after 12 weeks, measured by the combined score of the identification and discrimination subscales of the Sniffin’ Sticks testing battery. QoL, overall health, mood, personal well-being and symptom severity will be assessed at baseline and during a follow-up visit, using multiple validated questionnaires and scales. OT is offered to the second cohort during an open-label phase extension. This manuscript highlights and discusses the study protocol.Ethics and disseminationEthical approval for the study was obtained from the Ethics Commission of the Medical University of Innsbruck, Austria. Results of this study will be shared through conferences and publications in peer-reviewed journals.Trial registration numberNCT05421221.