Olfactory Function and Olfactory Disorders. / Riechen und Riechstörungen.

The sense of smell is important. This became especially clear to patients with infection-related olfactory loss during the SARS-CoV-2 pandemic. We react, for example, to the body odors of other humans. The sense of smell warns us of danger, and it allows us to perceive flavors when eating and drinking. In essence, this means quality of life. Therefore, anosmia must be taken seriously. Although olfactory receptor neurons are characterized by regenerative capacity, anosmia is relatively common with about 5 % of anosmic people in the general population. Olfactory disorders are classified according to their causes (e. g., infections of the upper respiratory tract, traumatic brain injury, chronic rhinosinusitis, age) with the resulting different therapeutic options and prognoses. Thorough history taking is therefore important. A wide variety of tools are available for diagnosis, ranging from short screening tests and detailed multidimensional test procedures to electrophysiological and imaging methods. Thus, quantitative olfactory disorders are easily assessable and traceable. For qualitative olfactory disorders such as parosmia, however, no objectifying diagnostic procedures are currently available. Therapeutic options for olfactory disorders are limited. Nevertheless, there are effective options consisting of olfactory training as well as various additive drug therapies. The consultation and the competent discussion with the patients are of major importance.

Disorders of smell and taste in COVID-19

Loss of smell is one of the symptoms most frequently reported by patients with COVID-19. Although the spontaneous cure rate is high, recent studies have shown that up to 7% of patients remain anosmic for more than 12 months after the onset of infection, leaving millions of people worldwide with severe olfactory dysfunction. Smell training is still the first recommended form of treatment. In view of the continued lack of approved drug treatment options, new therapeutic options are being explored. This article provides an overview of the current state of science on COVID-19-related olfactory disorders, with a focus on epidemiology, pathophysiology, cure rates, currently available treatments, and research into new treatments.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

[Olfactory and gustatory disorders]. / Riech- und Schmeckstörungen.

This manuscript aims to provide an overview of the etiology and diagnosis of olfactory and gustatory disorders. Not only are they common with about 5% of the population affected, but olfactory and gustatory disorders have recently gained attention in light of the rising SARS-CoV­2 pandemic: sudden loss of smell and/or taste is regarded as one of the cardinal symptoms. Furthermore, in the early diagnostics of neurodegenerative diseases, olfactory disorders are of great importance. Patients with olfactory dysfunction often show signs of depression. The impact of olfactory/gustatory disorders is thus considerable, but therapeutic options are unfortunately still limited. Following a description of the etiology, the diagnostic and therapeutic options are discussed on the basis of current literature. Potential future treatments are also addressed, e.g. autologous mucosal grafts or olfactory implants.

A Bayesian adaptive algorithm (QUEST) to estimate olfactory threshold in hyposmic patients

Objectives The sense of smell is important as a warning system, in social communication and in guiding food intake. Impairment is common, and cases are increasing following COVID-19. Olfactory dysfunction may lead to decreased quality of life. There are several established ways to assess olfaction including the "Sniffin' Sticks" which are a validated test for healthy and diseased populations. Methods The odor threshold is traditionally determined using a single staircase procedure, with narrow or wide step. We investigated a Bayesian adaptive algorithm (QUEST) to estimate olfactory threshold in a hyposmic population compared with a healthy control group. Thresholds were measured using the three procedures in two sessions (Test and Retest). Results All the tested methods showed considerable overlap in both groups: there was a positive correlation between the QUEST procedure and classic staircase method (r = 0.88), and high test-retest reliability for all three methods used (Sniffin' Sticks narrow: r = 0.81;Sniffin' Sticks wide: r = 0.95;QUEST: r = 0.80). Conclusions Results from these approaches exhibit considerable overlap with all of them being suitable for clinical use. An advantage of the QUEST method can be the defined number of trials needed to determine an odor threshold.

COVID-19 and olfactory dysfunction - an ENT perspective to the current COVID-19 pandemic

The current COVID-19 or Sars-CoV-2 pandemic increased awareness of hyposmia or anosmia, as this can be an accompanying symptom. In mild cases, anosmia without rhinorrhea can be the only presenting symptom of this infection. Timely identification can lead to early detection of otherwise asymptomatic carriers. History taking and essential clinical assessment with appropriate protective measures can be performed in patients in whom COVID-19 is suspected. Patients with anosmia without nasal obstruction should be considered COVID-19 suspect and this should initiate testing or self-isolation. As for treatment of hyposmia or anosmia, the authors do not advise treatment with systemic corticosteroids in patients with COVID-19. Based on expert opinion, nasal corticosteroids can be considered, with a preference for spray formulation. Patients who were already using topical or inhalation corticosteroids for proven pre-existing disease (such as asthma and/or allergy) should be advised to continue their maintenance therapy. ENT (Ear Nose Throat) focus on hyposmia and anosmia should be continued, to gain additional knowledge of the disease mechanisms of COVID-19 and improve follow-up, not only on the pneumological aspects but also to evaluate the impact on quality of life of potentially long-term side effects caused by anosmia.

Omega-3 supplementation in postviral olfactory dysfunction: a pilot study.

BACKGROUND: This study aimed to examine whether omega-3 supplementation would support olfactory recovery among postviral olfactory dysfunction patients. METHODOLOGY: Patients with postviral olfactory dysfunction were included in this non-blinded, prospective pilot study. Structured medical history was taken from the patients, including the following: age, sex, history of COVID-19 infection, and duration of symptoms. Patients were randomly assigned to receive olfactory training only (control group) versus olfactory training with omega-3 supplementation (treatment group). All patients exposed themselves twice a day to four odours (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory function was measured before and after training using 'Sniffin' Sticks', comprised of tests for odour threshold, discrimination, and identification. The average interval between olfactory tests was 3 months. RESULTS: Fifty-eight patients were included in the study, 25 men and 33 women. Generally, an improvement in olfactory scores was observed. Compared to the control group, the improvement in odour thresholds was more pronounced in the omega-3 group. Age, sex, and duration of symptoms had no effect on olfactory scores among both control and treatment groups. CONCLUSION: Overall, the present results indicate that omega-3 supplementation may be an option for adjunct therapy with olfactory training in patients with postviral olfactory dysfunction.

Applying olfactory bulb volume in the clinic: Relating clinical outcome measures to olfactory bulb volume using convolutional neural networks

The olfactory bulb (OB) plays a key role in olfactory processing;its volume is important for diagnosis, prognosis and treatment of patients with olfactory loss, e.g. due to a Covid-19 infection, neurodegenerative diseases or other causes. So far, measurements of OB volume have been limited to quantification of manually segmented OBs, which makes its application in large scale clinical studies infeasible. The aim of this study was to evaluate the potential of our previously developed automatic OB segmentation method for clinical measurements of OB volume. The method employs convolutional neural networks that localize the OBs and subsequently automatically segment them (Noothout et al., 2021). In previous work, we showed that this method accurately segmented the OBs resulting in a Dice coefficient above 0.8 and average symmetrical surface distance below 0.24 mm. Volumes determined from manual and automatic segmentations were highly correlated (r=0.79, p<0.001) and the method was able to recognize the absence of an OB. Here, we included MRI scans of 181 patients with olfactory loss from the Dutch Smell and Taste Center. OB volumes were computed from automatic segmentations as described above. Using a multiple linear regression model, OB volumes were related to clinical outcome measures. Age, duration and etiology of olfactory loss, and olfactory ability significantly predicted OB volume (F(5, 172) = 11.348, p<0.001, R2 = .248). The results demonstrate that our previously described method for automatic segmentation and quantification of the OB can be applied in both research and clinical populations. Its use may lead to more insight in and application of the OB in diagnosis, prognosis and treatment of olfactory loss. We aim to extend our research to other populations of patients with olfactory loss.

Achems clinical symposium: The cure for olfactory loss

The corona pandemic made it painfully clear to a broader public that there are limited options for the treatment of olfactory loss. Hence, the title of the symposium is provocative. Having said this, major advances in the understanding of olfactory loss have been made during the alst 20 years. Several options for treatment have been investigated, so that their possibilities and limitations are now clearer. The symposium will almost exclusively include presentations from medical doctors who see patients with olfactory loss on a daily basis. Speakers come from the USA, the UK and France, and all of them are widely recognized researchers. First, Katie Whitcroft form London will talk about corticosteroids which are the most frequently used drugs in the treatment of olfactory loss. Vijay Ramakrishnan from Aurora will deal with the nasal microbiome which may play a major role in olfactory loss. Andrew Lane from Baltimore will then talk about most recent advances in the understanding of the mechanisms of olfactory loss associated with inflammatory conditions - which are the cause of approximately 2/3 of all olfactory disorders, apart from aging. Finally, Moustafa Bensafi from Lyon will shed light on current developments in new therapeutic options including olfactory implants.

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

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

Expenditure of time of a routinely performed vascular surgery of a patient with COVID 19- A case report

Introduction The worldwide outbreak of COVID 19 is progressing rapidly and represents a challenge for public health systems and hospital facilities. Surgical wards shut down in order to increase the capacity of intensive care units and physicians. Nevertheless, patients with COVID 19 will need surgical procedures in future as well. Methods We report about our first experience, with respect to the expenditure of time, of a patient with a confirmed "SARS-Cov-2"infection in our clinic undergoing an explanation of a port catheter due to a catheter infection. Results Normally, the explanation of a port catheter is a routinely performed surgical procedure. The amount of work is low under usual conditions. Nevertheless, COVID 19 positive patients may be an exception. In this case the duration of the surgical procedure was 125 minutes, whereas the mean duration of the last five procedures was only 50 minutes. Furthermore the time-length of postoperative ward rounds is longer due to the additional necessary personal protection procedures. Conclusion Patients with a SARS-CoV-2 infection will be a challenge for surgical disciplines too as the logistic hygienic support is higher. Therefore surgical capacitiesmay be limited in future.

Assessment of Taste Function.

Taste disorders, impacting well-being and physical health, can be caused by many etiologies including the use of medication. Recently, taste disturbance is also considered as one of the predominant symptoms of COVID-19 although its pathogenesis requires further research. Localized taste disorders may be overlooked considering that whole-mouth taste perception is insured through several mechanisms. Individuals often fail to discern taste from flavor, and interviews/surveys are insufficient to properly assess taste function. Hence, various taste assessment methods have been developed. Among them, psychophysical methods are most widely applied in a clinical context. Less-biased electrophysiological, imaging, or morphological methods are used to a much lesser degree. Overall, more research is needed in the field of taste.

[Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview]. / Zukunftsweisende Therapieansätze bei Riechstörungen: elektrische Stimulation, Stammzelltherapie und Transplantation von Riechepithel ­ eine Übersicht.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

Erratum: Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population (Chem. Senses (2020) DOI: 10.1093/chemse/bjaa034)

This is a correction notice for article bjz034 (DOI: https://doi. org/10.1093/chemse/bjaa034), published on 22 May 2020. Due to an error in the script used to create subsections of Figure 1, there was both a shift in the intensity data and an erroneous calculation of error bars in all panels. Figure 1 and the accompanying figure legend have been revised to show the correct levels and error bars. This script error only affected visualization of the data in Figure 1 and did not impact the reported data or conclusions.(Figure Presented). © The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

[Temporary hyposmia in COVID-19 patients]. / Temporäre Hyposmie bei COVID-19-Patienten.

BACKGROUND: This is a report on the high incidence of olfactory dysfunction in COVID-19 patients in the first cohort of COVID-19 patients in Germany (Webasto cluster). METHODS: Loss of sense of smell and/or taste was reported by 26 of 63 COVID-19 patients (41%), whereas only 31% of the patients experiencing hyposmia had simultaneous symptoms of rhinitis. Smell tests were performed in 14 of these patients and taste tests in 10. The measurements were conducted in a patient care setting in an early COVID-19 cohort. RESULTS: An olfactory disorder was present in 10/14 patients, before as well as after nasal decongestion. In 2 of these patients, hyposmia was the leading or only symptom of SARS-CoV­2 infection. All tested patients reported recovery of smell and/or taste within 8 to 23 days. CONCLUSION: The data imply that a) COVID-19 can lead to hyposmia in a relevant number of patients, the incidence was approximately 30% in this cohort; b) in most cases, the olfactory disturbance was not associated with nasal obstruction, thus indicating a possible neurogenic origin; and c) the olfactory disorder largely resolved within 1-3 weeks after the onset of COVID-19 symptoms. There were no indications of an increased incidence of dysgeusia. These early data may help in the interpretation of COVID-19-associated hyposmia as well as in the counseling of patients, given the temporary nature of hyposmia observed in this study. Furthermore, according to the current experience, hyposmia without rhinitic obstruction can be the leading or even the only symptom of a SARS-CoV­2 infection.