Post-infectious Olfactory Dysfunction Research Articles

Comparative analyses of post-infectious olfactory dysfunction between COVID-19 and non-COVID-19 cases

To identify the differences between COVID-19-associated and non-COVID-19-associated olfactory dysfunction (OD), we analyzed demographic and clinical characteristics based on the causative virus (COVID versus non-COVID groups) in patients with post-infectious olfactory dysfunction (PIOD) who underwent the olfactory questionnaire and olfactory function test. Out of 169 patients with PIOD, 99 were diagnosed with COVID-19 (COVID group), while 70 were not (non-COVID group). The COVID group was younger and had a higher percentage of male patients as well as patients with parosmia than the non-COVID group. In the initial olfactory function tests, the TDI, discrimination and identification scores were significantly higher in the COVID group than in the non-COVID group. TDI scores were significantly increased in patients with PIOD after treatment, regardless of the group. The threshold score was significantly increased by 1.38 in the COVID group while the identification score was significantly increased by 2.67 in the non-COVID group. Patients with COVID-19-associated OD were younger in age, tended to be male, had a higher incidence of parosmia, and had better initial olfactory function test results compared to those with non-COVID-19-associated OD. Following treatment, odor detection threshold improved in the COVID group, whereas odor identification improved in the non-COVID group.

Parosmia in patients with post-infectious olfactory dysfunction in the era of COVID-19-associated olfactory impairment.

Alarge number of patients with olfactory impairment are affected by parosmia or phantosmia. This study aimed to examine the demographic and clinical characteristics of parosmia. We performed aretrospective data analysis of patients consulting at our Smell and Taste Outpatient Clinic. Atotal of 297 patients were included (203 women, mean age44.4 ± 13.7years). Olfactory function was quantified using the "Sniffin' Sticks" composite TDI (odor threshold, determination, and identification) score. The presence of qualitative olfactory impairment was assessed trough medical history and aparosmia questionnaire. Most of the patients showed olfactory impairment after an infection with SARS-CoV‑2 (84%) and were diagnosed with parosmia (49%). Patients with parosmia (PAR) (n = 201) were significantly younger compared to the group without parosmia (noPAR; n = 92) (PAR 43.2 ± 13years vs. noPAR 47 ± 15.1 years, p = 0.03) and had aslightly shorter duration of disease, without reaching statistical significance (PAR 10.3 ± 4.9months, noPAR 13.6 ± 37.6 months, p = 0.23). They also had higher TDI scores (PAR 24.3 ± 7points, noPAR 21.4 ± 8.2points, p = 0.003). Patients affected by parosmia were younger and had abetter olfactory function compared to patients without parosmia.

Olfactory event-related potentials (OERPs) and trigeminal event-related potentials (TERPs) in subjects after Covid-19 infection: single-center prospective study.

Olfactory dysfunction (OD) is a common symptom associated with Covid-19. During the Covid-19 pandemic, the importance of psychophysical olfactory tests and electrophysiological olfactory assessment increased. The purpose of the study was to analyze the psychophysical olfactory tests and the post-covid curves of olfactory event-related potentials (OERPs) and trigeminal event-related potentials (TERPs). The prospective study included 98 subjects (62 females / 36 males). The average age was 42 years (range 21-84 years). Group I (n = 77) contained participants who had been infected with Covid-19. They were enrolled in the study at least 1 year after Covid-19. Group II (n = 21) was the healthy normosmic control group. In Group I, the OERPs of 18% participants were absent. Patients in Group I were statistically more likely to have an absence of OERPs (p = 0.036) than subjects in Group II. We did not detect a statistical difference in amplitudes and latencies of the OERPs between Group I and Group II. In Group I, N1 latency of the TERPs was significantly longer (p = 0.002) than in Group II. The amplitude of the N1-P2 interval of the TERPs was significantly lower (p = 0.025) in Group I than in Group II. According to the psychophysical Sniffin stick identification test, hyposmia was detected in 39% in Group I versus 0% in the control Group II. OD is a common post-covid symptom. The presence of OERPs is a significant prognostic factor for olfactory function after Covid 19. We detected a lower percentage of absence of OERPs after Covid-19 compared to the previously published studies of post-viral OD and post-infectious OD. For TERPs, we detected a longer N1 latency and a lower amplitude for the N1-P2 interval after Covid-19. OERPs and TERPs can be considered valid biomarkers to evaluate the progress of post-covid OD.

Combination of Acupuncture and Daily Olfactory Training for a patient with Postinfectious Olfactory Dysfunction

Combination of Acupuncture and Daily Olfactory Training for a patient with Postinfectious Olfactory Dysfunction

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study

ObjectiveTo determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). MethodsWe conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. ResultsOverall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. ConclusionThe present study showed that TSS and mecobalamin might be useful for treating PIOD.

Interpretation of the 2021 American Academy of Allergy, Asthma and Immunology expert consensus on the treatment of postinfectious olfactory dysfunction

Respiratory tract viruses are the second leading cause of olfactory dysfunction. Between 2019 to 2022, the world has been plagued by the problem of olfaction caused by the COVID-19. As we learn more about the impact of severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）, with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction（PIOD）. The Clinical Olfactory Working Group has proposed theconsensus on the roles of PIOD. This paper is the detailed interpretation of the consensus.

Comparative Analysis of Olfactory and Gustatory Function of Patients With COVID-19 Olfactory Dysfunction and Non-COVID-19 Postinfectious Olfactory Dysfunction.

Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have evaluated these symptoms using subjective surveys and simple olfactory tests only. Hence, we compared the olfactory and gustatory characteristics of patient groups with COVID-19 olfactory dysfunction (C19OD) and non-COVID-19 postinfectious olfactory dysfunction (PIOD) using an objective olfactory test and evaluated the significance of olfactory training in both patient groups. We retrospectively analyzed the medical records of 14 patients with a decreased sense of smell after having positive COVID-19 polymerase chain reaction results, and 56 patients with PIOD with no history of confirmed COVID-19. Participants were evaluated using the Korean version of the Sniffin' stick (KVSS) II, and chemical gustometry and olfactory training was assessed during their first visit. Olfactory training was then re-evaluated after an average of 8 (± 6) weeks. The average age of participants in the C19OD group was lower than in those in the non-COVID-19 PIOD group. The proportion of men in the C19OD group was higher than in the non-COVID-19 PIOD group. At baseline assessment, the C19OD group had better olfactory and gustatory functions. After olfactory training, the non-COVID-19 PIOD patient group showed a significant increase in all KVSS II Total, T, D, and I scores, but there was a non-significant increase in all scores in the C19OD group. The C19OD group had better olfactory and gustatory function than the non-COVID-19 PIOD group at the initial assessment. After olfactory training, there was an increase in olfactory function test scores in both groups. Olfactory training may be helpful in C19OD, as in non-COVID-19 PIOD.

A multicenter real-life study to determine the efficacy of corticosteroids and olfactory training in improving persistent COVID-19-related olfactory dysfunction.

No definitive treatment exists to effectively restore function in patients with persistent post-infectious olfactory dysfunction (OD). Corticosteroids have been considered as a therapeutic option in post-infectious OD but their benefit in COVID-19-related OD remains unexplored. We aim to determine the role of the combination of corticosteroids plus olfactory training (OT) in improving persistent COVID-19-related OD. A multicenter real-life cohort study was conducted between December 2020 and April 2022 on patients with reported COVID-19-related OD. Only patients with confirmed OD at Sniffin' Sticks (S'S) and those who attended their 6-month follow-up were included. Patients were started on a combined treatment of corticosteroids and OT. Patients refusing corticosteroids or not doing any treatment formed the control groups. Visual analogue scale (VAS) for sense of smell and SNOT-22 were used to assess patients reported symptoms. Sixty-seven subjects with reported COVID-19-related OD were initially seen. Normosmic patients at S'S (n=14) and those not attending their follow-up (n=9) were excluded. Of the 44 patients included in the analysis, 19 patients had the combined treatment (group A), 16 patients refused to take corticosteroids and did the OT alone (group B) whereas 9 patients did not do any treatment (group C). An improvement of threshold + discrimination + identification (TDI) score (p=.01) and VAS for smell (p=.01) was found in group A whereas only the TDI score improved in group B (p=.04). Presence of comorbidities, age, sex (male), and length of OD negatively influenced olfactory recovery. Our study confirms the importance of OT in long-term OD suggesting that the addition of corticosteroids may give a benefit in terms of patient's perceived olfaction. 2b.

Practical Review of Olfactory Training and COVID-19

Olfactory disorders one of the most frequent distinctive symptoms of COVID-19 infection. COVID-19-induced olfactory disorder can be classified as post-infectious olfactory dysfunction (PIOD). The effect of drugs on olfactory disorder following upper respiratory infection, including PIOD, has not been clearly established, which adds to the difficulty with treating the disorder. However, the effect of olfactory training on PIOD has been confirmed by numerous studies. As such, olfactory training is gaining attention, and has taken on greater importance, as the sole treatment for COVID-19–induced olfactory disorder in this pandemic age. This review describes the effect of olfactory training for COVID-19–induced olfactory disorder by analyzing the relevant literature.

Ask the Experts: An International Consensus on Managing Post-Infectious Olfactory Dysfunction Including COVID-19.

Purpose of ReviewTo summarise the current understanding of post-infectious olfactory dysfunction (PIOD) and provide a consensus on management of the condition through an evidence-based approach, critically reviewing the available management options.Recent FindingsNew studies investigating the pathophysiology of PIOD in COVID-19 patients have found that in those with persistent symptoms there is an association with lower tissue perfusion in the orbital and medial regions of the frontal lobe. Recent meta-analyses have listed olfactory training as the first line management for PIOD.SummaryOlfactory training remains the most recommended management option for PIOD. The use of systemic corticosteroids to treat PIOD is not encouraged due to poor evidence.

Long-term quality-of-life impairment in patients with more than 1-year COVID-19-related olfactory dysfunction.

Long-term quality-of-life impairment in patients with more than 1-year COVID-19-related olfactory dysfunction.

Smell and Taste Dysfunctions owing to COVID-19

Olfactory and taste dysfunctions are characteristic symptoms of coronavirus disease 2019 (COVID-19); however, their frequencies and pathogeneses keep changing because of rapid mutations of the viral strains. Angiotensin-converting enzyme 2, a receptor for the spike protein of SARS-CoV-2 in the olfactory epithelium, is involved in the development of olfactory dysfunction. In general, olfactory dysfunctions resolve in a few weeks. However, there are cases wherein the symptoms persist for several months or longer, and parosmia or phantosmia affects the patient's quality of life. It is also assumed that the damage owing to COVID-19 extends to olfactory nerve cells, resulting in sensorineural olfactory dysfunction similar to post-infectious olfactory dysfunction.

Depression Symptoms and Olfactory-related Quality of Life.

ObjectivesPatients with olfactory dysfunction (OD) frequently report symptoms of depression. The objective of this study was to determine how clinical characteristics and olfactory‐related quality of life (QoL) measures associate with the likelihood for major depressive disorders (MDDs).MethodsA total of 192 OD patients were included. Olfactory function was measured using all three subtests of the Sniffn' Sticks test. Olfactory‐related quality of life (QoL) was evaluated using the Questionnaires of Olfactory Dysfunction (QOD)‐negative (NS) and ‐positive statement (PS). The likelihood for MDD was assessed using the Patients Health Questionnaire‐2 (PHQ‐2). Demographics and disease‐specific variables (etiology and duration of OD) were collected. Univariate and multivariable analyses were used to associate disease‐specific variables and the QOD with the outcome of the PHQ‐2. Additionally, the predictive ability of the QOD‐NS to predict depressive symptoms was calculated.ResultsIn univariate analysis, COVID‐19 related smell loss, the QOD‐NS, and the QOD‐PS were significantly associated with the PHQ‐2. In multivariable analyses adjusting for QoL measures, the QOD‐NS (ß = 0.532, p < 0.001) and sinonasal OD (compared with postinfectious OD) were significantly associated with the PHQ‐2 (ß = 0.146, p = 0.047). When omitting QoL measures from multivariable analyses, only COVID‐19 related OD (compared with postinfectious OD) was significantly associated with the PHQ‐2 (ß = 0.287, p = 0.009). A QOD‐NS score > 20.5 had 70.13% sensitivity and 76.32% specificity for detecting symptoms of depression.ConclusionOur results suggest that COVID‐19 related OD might be associated with a higher likelihood for MDD. Furthermore, we showed that the QOD‐NS score might be helpful to predict symptoms of depression in OD patients.Level of Evidence4 Laryngoscope, 132:1829–1834, 2022

Postinfectious Olfactory Complaints: A Follow-up Study.

Introduction Acute upper respiratory infection (AURI) is the most common cause of postinfectious olfactory dysfunction (PIOD). Objective We investigated the prevalence of PIOD in a large group of patients reporting persistent smell impairment perception after the AURI resolution. Methods Olfactometry was performed within 1 month after the common cold resolution and after 1 year in 467 (299 males, mean age 41.7 years) outpatients. The Sniffin' Sticks olfactory test (Burghart instruments, Wedel, Germany) was used. Results Anosmia was documented in 28 (6%) patients, hyposmia in 33 (7%), and cacosmia in 55 (11.7%). After 1 year, PIOD improved in 82 (79.6%) patients re-tested. Conclusion The current study demonstrated that persistent olfactory dysfunction is a relevant symptom in patients with AURI, even though many patients had normal olfactometry. Thus, smell impairment deserves careful attention and requires objective documentation.

The Role of Social Media in Improving Patient Recruitment for Research Studies on Persistent Post-Infectious Olfactory Dysfunction.

Background and Objectives: Since the COVID-19 pandemic, the number of cases of post-infectious olfactory dysfunction (PIOD) has substantially increased. Despite a good recovery rate, olfactory dysfunction (OD) becomes persistent in up to 15% of cases and further research is needed to find new treatment modalities for those patients who have not improved on currently available treatments. Social media has emerged as a potential avenue for patient recruitment, but its role in recruiting patients with smell dysfunction remains unexplored. We conducted a survey using the AbScent Facebook page to evaluate the feasibility of using this platform for future studies on smell dysfunction. Materials and Methods: Between 26 October and 4 November 2021, we conducted an online survey to evaluate propensity of patients with PIOD who would be willing to participate in research studies on smell dysfunction. Results: Sixty-five subjects were surveyed with a response rate of 90.7%. The median visual analogue scale (VAS) for sense of smell was 0 at infection and 2 at survey completion. The median length of OD was 1.6 years, and the main cause of OD was SARS-CoV-2 (57.6%). Parosmia was reported in 41 subjects (69.5%) whilst phantosmia in 22 (37.3%). The median length of olfactory training (OT) was 6 months but subjectively effective in 15 subjects (25.4%). Twenty-seven subjects (45.8%) tried other medications to improve olfaction, but only 6 participants (22.2%) reported an improvement. All subjects expressed their propensity to participate in future studies with most of them (38; 64.4%) willing to be enrolled either in medical and surgical studies or to be part of a randomised study design (11; 18.6%). Conclusions: Using the AbScent Facebook platform we successfully selected a population of subjects with persistent and severe OD that have failed to improve on available treatments and are willing to participate in further clinical trials.

Patients’ Perspectives on Qualitative Olfactory Dysfunction: Thematic Analysis of Social Media Posts

BackgroundThe impact of qualitative olfactory disorders is underestimated. Parosmia, the distorted perception of familiar odors, and phantosmia, the experience of odors in the absence of a stimulus, can arise following postinfectious anosmia, and the incidences of both have increased substantially since the outbreak of COVID-19.ObjectiveThe aims of this study are to explore the symptoms and sequalae of postinfectious olfactory dysfunction syndrome using unstructured and unsolicited threads from social media, and to articulate the perspectives and concerns of patients affected by these debilitating olfactory disorders.MethodsA thematic analysis and content analysis of posts in the AbScent Parosmia and Phantosmia Support group on Facebook was conducted between June and December 2020.ResultsIn this paper, we identify a novel symptom, olfactory perseveration, which is a triggered, identifiable, and usually unpleasant olfactory percept that persists in the absence of an ongoing stimulus. We also observe fluctuations in the intensity and duration of symptoms of parosmia, phantosmia, and olfactory perseveration. In addition, we identify a group of the most common items (coffee, meat, onion, and toothpaste) that trigger distortions; however, people have difficulty describing these distortions, using words associated with disgust and revulsion. The emotional aspect of living with qualitative olfactory dysfunction was evident and highlighted the detrimental impact on mental health.ConclusionsQualitative and unsolicited data acquired from social media has provided useful insights into the patient experience of parosmia and phantosmia, which can inform rehabilitation strategies and ongoing research into understanding the molecular triggers associated with parosmic distortions and research into patient benefit.

A Comparative Olfactory MRI, DTI and fMRI Study of COVID-19 Related Anosmia and Post Viral Olfactory Dysfunction

Rationale and ObjectiveTo evaluate how COVID-19 anosmia imaging findings resembled and differed from postinfectious olfactory dysfunction (OD).Material and MethodsA total of 31 patients presenting with persistent COVID-19 related OD and 97 patients with post-infectious OD were included. Olfactory bulb MRI, DTI and olfactory fMRI findings in both groups were retrospectively assessed.ResultsAll COVID-19 related OD cases were anosmic, 18.6% of post-infectious OD patients were hyposmic and remaining 81.4% were anosmic. Mean interval between onset of OD and imaging was 1.5 months for COVID-19 related OD and 6 months for post-infectious OD.Olfactory bulb volumes were significantly higher in COVID-19 related OD than post-infectious OD. Deformed bulb morphology and increased olfactory bulb signal intensity was seen in 58.1% and 51.6% with COVID-19 related OD; and 63.9% – 46.4% with post-infectious OD; without significant difference. Significantly higher rate of olfactory nerve clumping and higher QA values at orbitofrontal and entorhinal regions were observed in COVID-19 related OD than post-infectious OD.Absence of orbitofrontal and entorhinal activity showed no statistically significant difference between COVID-19 related OD and post-infectious OD, however trigeminosensory activity was more robust in COVID-19 related OD cases.ConclusionOlfactory bulb damage may play a central role in persistent COVID-19 related anosmia. Though there is decreased olfactory bulb volume and decreased white matter tract integrity of olfactory regions in COVID-19 related anosmia, this is not as pronounced as in other post-infectious OD. Trigeminosensory activity was more robust in COVID-19 related OD. These findings may reflect better preserved central olfactory system in COVID-19 related OD compared to COVID-19 related OD.

Treatment of Postinfectious Olfactory Dysfunction Using Corticosteroids.

This study aimed to analyze the efficacy of different doses and forms of corticosteroids in the treatment of postinfectious olfactory dysfunction and to specify the factors related to the curative effects. The medical records of patients diagnosed with postinfectious olfactory dysfunction from January 2018 to May 2019 were reviewed. All patients received different doses of oral corticosteroids for 12 days or inhaled corticosteroids for 1 month. A review of the records of 43 patients showed that the mean follow-up time was 6.66 months, and the overall effective rate of treatment was 48.8%. Postinfectious olfactory dysfunction exhibited distinct seasonality, with the highest incidence in March. The curative effect was significantly related to the olfactory discrimination threshold at the first consultation (P = .022), but not significantly associated with age (P = .325), sex (P = .924), duration of disease (P = .526), follow-up time (P = .489), or treatment program (P = .330). Different doses and forms of corticosteroids showed no significant difference in the therapeutic effect on postinfectious olfactory dysfunction. The olfactory discrimination threshold at the first consultation was the most important factor influencing the prognosis.

Postinfectious Olfactory Dysfunction: Oral Steroids and Olfactory Training versus Olfactory Training Alone: Is There any Benefit from Steroids?

Introduction: There are limited treatment options for postinfectious olfactory dysfunction (PIOD). Olfactory training has recently been used in clinical practice, but no medical treatment is widely accepted. Although there is weak evidence for their value, some physicians use oral corticosteroids as first-line treatment. The aim of this study was to compare combined oral methylprednisolone and olfactory training with olfactory training alone in the management of PIOD. Methods: This prospective cohort study included 131 patients with PIOD over a 2-year period before the COVID-19 pandemic. Seventy-eight patients who were treated with oral methylprednisolone and olfactory training (group A) were compared with 53 patients who were treated with olfactory training only (group B). Olfactory function was evaluated with “Sniffin’ Sticks” at baseline and 2, 8, and 16 weeks after initial assessment. Patients who improved after steroid treatment underwent magnetic resonance imaging of the paranasal sinuses, skin prick tests, lung spirometry, and sputum eosinophil assessment. Results: Oral steroids improved 19.23% of patients (n = 15) of group A. History, clinical evaluation, imaging, and laboratory tests identified an inflammatory background in half of them (n = 8). The remaining 7 had no findings of nasal inflammation, and all had a short history of olfactory dysfunction. Both groups significantly improved in olfactory testing results at the end of the olfactory training scheme without significant difference between them. Conclusions: The percentage of improved patients after oral methylprednisolone was relatively low to suggest it as first-line treatment. Half of the improved patients had an underlying upper airway inflammatory condition not related to the infection that caused the acute loss of olfactory function.

Smell Training in Prolonged COVID-19 PostInfectious Olfactory Dysfunction: A Case Report

ABSTRACT&#x0D; Objective: To report the case of a woman who underwent smell training for post-infectious olfactory dysfunction presumably from COVID-19.&#x0D; Methods:&#x0D; Design: Case Report&#x0D; Setting: Tertiary Private Training Hospital&#x0D; Patient: One&#x0D; Result: A 41-year-old woman who developed olfactory dysfunction attributed to COVID-19 underwent smell training. At baseline, her responses were mostly “no smell,” and those reported as “can smell a bit” were rated as distorted. After three months, she could now smell items that she previously could not smell, but these smells were still distorted. At the time of this writing, she was on her 4th month of smell training.&#x0D; Conclusion: Although we cannot rule out spontaneous resolution of anosmia in our patient, we would like to think that smell training contributed to her recovery of smell.