Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study.

OBJECTIVE: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection. METHODS: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. RESULTS: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). CONCLUSION: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations.

The Olfactory Dysfunction of COVID-19.

Until the coronavirus disease 2019 (COVID-19) pandemic, much of the scientific community and the general public lacked an appreciation of the impact of decreased smell function on everyday life, including the importance of this sensory system for safety, nutrition, and overall quality of life. It is now well established that the SARS-CoV-2 virus inflicts measurable but frequently reversible smell loss during its acute phase. Indeed, in many studies such loss is the most common symptom of COVID-19. Permanent or long-term deficits (i.e., deficits lasting over a year) may occur in up to 30% of those who have been infected, including the development of odor distortions (dysosmias; parosmias). This review presents up-to-date information on the epidemiology, severity, and pathophysiology of COVID-19-related smell dysfunction, including its association with psychological and neurological sequelae.

[Olfaction and respiratory viruses A relationship revealed by Covid-19]. / Odorat et virus respiratoires :une relation révélée par la Covid-19.

The sense of smell has been underestimated for a long time in humans. It has been brought to the fore by its sudden disappearance during the Covid-19 pandemic of which anosmia (complete loss of smell) is one of the major symptoms. However, respiratory viruses have long been associated with smell disorders, 25% of which are linked to a viral infection. Olfaction begins in the nose within the olfactory epithelium which has the particularity of containing neurons in direct contact with the environment. Several respiratory viruses are known for their replicative capacity within this epithelium. This is particularly the case for the flu virus (influenza) and bronchiolitis (respiratory syncytial virus) but their tropism for this tissue is much lower than SARS-CoV-2. The understanding of the SARS-CoV-2 pathophysiology in the nasal cavity makes it possible to reveal part of the links between viral infection and olfactory disorders.

Title: Odorat et virus respiratoires :une relation révélée par la Covid-19. Abstract: L'odorat, sens pendant longtemps sous-estimé chez l'homme, a été mis sur le devant de la scène par sa soudaine disparition, survenue pendant la pandémie de Covid-19, dont l'anosmie est un des symptômes majeurs. Pourtant, depuis longtemps, les virus respiratoires ont été associés aux troubles de l'odorat, dont 25 % seraient liés à une infection virale. L'olfaction débute dans le nez, au sein d'un épithélium olfactif qui a la particularité de contenir des neurones en contact direct avec l'environnement. Plusieurs virus respiratoires sont connus pour leur capacité réplicative au sein de cet épithélium. C'est notamment le cas du virus de la grippe (influenza) et du virus de la bronchiolite (VRS, pour virus respiratoire syncytial), mais leur tropisme pour ce tissu est bien moindre que celui du SARS-CoV-2. La physiopathologie de ce virus dans la cavité nasale a permis de commencer à comprendre les liens existant entre une infection virale et les troubles de l'olfaction.

Olfactory-related quality of life impacts psychological distress in people with COVID-19: The affective implications of olfactory dysfunctions.

BACKGROUND: Coronavirus disease 2019 (COVID-19) often causes chemosensory impairment, and olfactory dysfunctions may have negative consequences on psychological distress. This study aimed at assessing which dimension of perceived olfactory disfunctions (i.e., subjective olfactory capability, smell-related problems, or olfactory-related quality of life [QoL]) was most associated with psychological distress in people diagnosed with COVID-19. METHODS: 364 participants (65 men and 299 women) diagnosed with COVID-19 on average 7 months prior to the beginning of the study were recruited between June 5 and 21, 2021, to take part in an online cross-sectional survey. Participants answered questions on demographics, clinical factors, perceived olfactory functioning, and psychological distress. Hierarchical multiple linear regression analysis was conducted, assessing the role of demographics, clinical factors, and perceived olfactory functioning dimensions on psychological distress. RESULTS: More than half of the participants met the cut-off for all perceived olfactory dysfunctions scales and psychological distress. Being women, smoker, with comorbidities, and greater severity of COVID-19 symptoms were associated with higher scores on psychological distress. Among perceived olfactory functioning scales, only impairment in olfaction QoL was associated with psychological distress. LIMITATIONS: Limitations concerned the cross-sectional nature of the study and the unbalanced sample in terms of gender. CONCLUSIONS: The study confirmed the core intertwining between mood, perceived QoL, and olfactory functioning, showing how impairments in olfactory processing are strongly correlated with psychological distress through the impact they have on the perceived QoL.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Persistent olfactory dysfunction in mild COVID-19 patients: A descriptive study of the characteristics and association with other symptoms.

INTRODUCTION: Post-COVID olfactory dysfunction continues to be studied due to the controversy of the mechanisms involved. The aim was to investigate the olfactory dysfunctions in association with other post-COVID symptoms. MATERIAL AND METHODS: Observational, descriptive and single-center study. The patients had confirmed mild COVID-19 and subjective olfactory dysfunction of more than a month of evolution, which was assessed by Sniffin' Sticks Olfactory Test. RESULTS: A total of 86 patients participated. The mean age was 37.2 years (SD 9.82). 70.9% reported parosmia and 46.5% symptoms of brain fog. A pathological test result was obtained in 72.1% of the participants. The most failed pen was 11 (apple) in 76.7%. Anosmia of pen 15 (anise) was reported more frequently in 24.4% and cacosmia of pen 9 (garlic) in 27.9%. We observed a significant association between patients who reported parosmias and brain fog (RR 2.18; p=0.018), also between parosmia and phantosmia (RR 6.042; p<0.001). CONCLUSION: There is some pathological selectivity for certain test pens, a higher prevalence of cognitive symptoms and many patients with combined parosmia and brain fog.

High prevalence of olfactory impairment among leprosy patients: A cross-sectional study.

BACKGROUND: The effect of leprosy on the sense of smell is not yet fully established. Studies that have relied only on patients' perceptions may have under- or over-estimated the change in smell perception. A validated and psychophysical method is necessary to avoid these errors in assessment. OBJECTIVES: This study aimed to validate the existence of olfactory involvement in leprosy patients. METHODS: A cross-sectional, controlled study was conducted, in which individuals with leprosy (exposed individuals) and individuals without leprosy (control patients) were recruited. For each exposed individual, we selected two control patients. A total of 108 patients (72 control patients and 36 exposed individuals) with no history of infection with the new coronavirus (COVID-19) took the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Most exposed individuals had olfactory dysfunction [n = 33, 91.7% (CI 95%: 77.5%-98.3%)] when compared with the control patients [n = 28, 38.9% (CI 95%: 27.6%-51.1%)], but only two (5.6%) had olfactory complaints. The olfactory function was significantly worse among exposed individuals [UPSIT leprosy = 25.2 (CI 95%: 23.1-27.3) when compared with the UPSIT control patients = 34.1 (CI 95%: 33.0-35.3); p<0.001]. The risk of olfactory loss was higher among the exposed individuals [OR: 19.5 (CI 95%: 5.18-105.70; p < 0.001)]. CONCLUSIONS: Olfactory dysfunction was highly prevalent among exposed individuals, although they had little or no self-knowledge of the disorder. The results show that it is important to assess the sense of smell in exposed individuals.

Recovery from Covid-19 smell loss: Two-years of follow up.

OBJECTIVE: To report long-term patterns of recovery and non-recovery in a large nationwide cohort of subjects with COVID-19 associated smell loss. STUDY DESIGN: Prospectively, longitudinal questionnaires. SETTING: Web-based national survey. METHODS: A longitudinal survey of adults with COVID-19 and/or sudden change in smell or taste since January 1, 2020 was launched April 10, 2020. Participants were queried again in late May 2022 regarding recovery. Data from respondents with >2 years since loss were analyzed and compared to recovery status of those more recently effected. RESULTS: 1103 responded to the survey of whom 946 met inclusion criteria. Among the 267 respondents for whom at least 2 years of follow up was available, 38.2 % reported full recovery, 54.3 % partial, and 7.5 % no recovery. For the entire cohort (all with ≥3 months since smell loss), 38.7 % reported complete recovery, 51.0 % reported partial recovery (ranging from mild complaints to severe phantosmia or dysosmia), and 10.3 % reported no improvement at all. Complete recovery of smell function was significantly higher in those under 40 years old (45.6 % compared to 32.9 % in those over 40). CONCLUSION: Although the vast majority of subjects who do recover do so within the first 3 months, long-term spontaneous recovery can occur. Rates of recovery do not seem to differ depending on when during the pandemic the loss first occurred.

[Parosmia and phantosmia: clinical update]. / Parosmie et fantosmie: mise à jour.

Olfactory disorders became known by large parts of the population since the Covid-19 pandemic. The causes of olfactory dysfunctions are manifold. Similar to other sensory impairments the disruption can be qualitative or quantitative. Quantitative olfactory disorders such as anosmia or hyposmia are well explored, whereas the knowledge on qualitative disorders such as parosmia or phantosmia is still limited. This article gives an update on the current clinical knowledge and workup of parosmia and phantosmia.

Depuis la pandémie de Covid-19, la population est davantage informée sur les troubles de l'odorat. Ils peuvent être d'origines multiples. Comme pour toute modalité sensorielle, il existe des atteintes quantitatives et qualitatives. Les troubles quantitatifs sont mieux connus et pris en charge mais les troubles qualitatifs restent méconnus. Cet article traite des troubles de l'odorat qualitatifs, notamment de la parosmie et de la fantosmie, ainsi que de leur prise en charge.

Natural trajectory of recovery of COVID-19 associated olfactory loss.

IMPORTANCE: Prevalence of post-viral olfactory loss has increased dramatically due to the frequency and severity of olfactory dysfunction associated with infection by the SARS-CoV-2 virus. OBJECTIVE: To determine the trajectory of COVID-19 olfactory loss over a six-month period. A key secondary objective is to assess predictive factors associated with the recovery of olfaction. DESIGN: Longitudinal repeated-measures study that enrolled from May 5, 2020 to February 2, 2021, with the last date of data collection on June 15, 2021. SETTING: Barnes-Jewish HealthCare/Washington University School of Medicine facilities (Saint Louis, Missouri, USA). PARTICIPANTS: Individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction on nasopharyngeal swab and indicated olfactory loss on COVID-19 screening questionnaire. Individuals were excluded if they had previously diagnosed history of olfactory loss, neurodegenerative disorders, <18 years of age, admitted to hospital service, unable to read, write, and understand English, or lacked computer or internet access. INTERVENTIONS/EXPOSURES: Watch and wait for spontaneous recovery. MAIN OUTCOME(S) AND MEASURE(S): Participants completed olfactory assessments every 30 days for six months. Each assessment consisted of the University of Pennsylvania Smell Identification Test (UPSIT), an objective "scratch-and-sniff" test, and Clinical Global Impressions (CGI), a subjective Likert rating scale. RESULTS: The mean age was 41 years old (SD = 16). 39 (80 %) were female and 42 (86 %) white. At baseline assessment of objective olfaction, 18 (36 %) participants had anosmia or severe hyposmia. Subjective, complete recovery at six months was 81 % (95 % CI 74 % to 88 %). Likelihood of recovery was associated with age <50 years (aHR = 8.1 (95 % CI 1.1 to 64.1)) and mild olfactory loss at baseline (UPSIT = 30-33 for males and 31-34 for females) (aHR 6.2 (95 % CI 1.2 to 33.0)). CONCLUSIONS AND RELEVANCE: The trajectory of olfactory recovery among adults with COVID-19 olfactory loss illustrated rapid recovery within 2-3 weeks of infection, and by six months 81 % had recovered based on self-report. Age <50 years old and mild severity of olfactory loss at baseline were associated with increased likelihood of recovery of olfaction. These findings can be used to inform shared decision-making with patients.

Prevalence of taste and smell dysfunction in mild and asymptomatic COVID-19 patients during Omicron prevalent period in Shanghai, China: a cross-sectional survey study.

OBJECTIVES: COVID-19, which is caused by SARS-CoV-2, is a severe threat to human health and the economy globally. This study aimed to investigate the prevalence of taste and/or smell dysfunction and associated risk factors in mild and asymptomatic patients with Omicron infection in Shanghai, China.DesignThis was a questionnaire-based cross-sectional study. SETTING: COVID-19 patients at the makeshift hospital in the Shanghai World Expo Exhibition and Convention Centre were recruited from March to April 2022. PARTICIPANTS: In total, 686 COVID-19-infected patients who were defined as mild or asymptomatic cases according to the diagnostic criteria of New Coronavirus Pneumonia Prevention and Control Programme ninth edition (National Health Commission of China, 2022) were enrolled. MEASURES: Data to investigate taste and smell loss and to characterise other symptoms were collected by the modified Chemotherapy-induced Taste Alteration Scale and Sino-Nasal Outcome Test-22 questionnaires. The risk factors for the severity of taste/smell dysfunction were analysed by binary logistic regression models. RESULTS: 379 males (379/686, 55.2%) and 307 females (307/686, 44.8%) completed the questionnaires to record recent changes in taste and smell ability. A total of 302 patients (44%) had chemosensory dysfunction with Omicron infection, of which 22.7% (156/686) suffered from both taste and smell dysfunction. In addition, cough (60.2%), expectoration (40.5%), fever (33.2%) and sore throat (32.5%) were common symptoms during Omicron infection. The quality-of-life-related indicators were negatively associated with participants' self-reported taste and smell dysfunction. CONCLUSIONS: The prevalence of taste or/and smell dysfunction in patients with Omicron infections was 44%. Individuals with chemosensory dysfunction had significantly higher rates of various upper respiratory influenza-like symptoms, xerostomia and bad breath. Moreover, smell dysfunction was a risk factor for the prevalence of taste dysfunction in patients with Omicron infection. TRIAL REGISTRATION NUMBER: ChiCTR 2200059097.

Long-term Consequences of COVID-19: Chemosensory Disorders.

PURPOSE OF REVIEW: A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies. RECENT FINDINGS: Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3 months to 2 years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.

The incidence and impact of anosmia on daily life after COVID-19 infection: A cross-sectional study in a tertiary center in Saudi Arabia.

OBJECTIVES: To investigate the impact of olfactory dysfunction's (OD) on patients with coronavirus disease-19 (COVID-19) and evaluate the risk factors associated with it. METHODS: This cross-sectional study analyzed patients who tested positive for COVID-19 over a period of 4 months (May-July 2020) and experienced OD and mild illness. Selected patients were given 2 scales Olfactory Disorders Negative Statement (QOD-NS) and Sino-nasal Outcome Test (SNOT-22). RESULTS: A total of 256 patients were enrolled, out of which 196 had anosmia after COVID-19 infection. More than 75% of the participants were aged between 20-40 years and 64.3% were women. The mean score of the patients was 25.13 (SD 19.6) on the SNOT-22, while it was 4.9 (SD 4.85) on the QOD-NS. There was no association between anosmia and other comorbidities and factors (age, smoking history, allergic rhinitis history, asthma, and so on). Only 39% of patients who had anosmia after COVID-19 recovered in less than 4 months. CONCLUSION: Olfactory dysfunction is a common symptom of COVID-19 infection and it can take more than 4 months to recover. Nevertheless, this cohort reports a moderate impact on their quality of life due to anosmia.

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-Analysis.

The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review and meta-analysis provide information regarding regional differences in prevalence as well as an estimate of the global prevalence of olfactory dysfunction based on 62 studies reporting information on 626,035 patients infected with the omicron variant. Our estimate of the omicron-induced prevalence of olfactory dysfunction in populations of European ancestry is 11.7%, while it is significantly lower in all other populations, ranging between 1.9% and 4.9%. When ethnic differences and population sizes are considered, the global prevalence of omicron-induced olfactory dysfunction in adults is estimated to be 3.7%. Omicron's effect on olfaction is twofold to tenfold lower than that of the alpha or delta variants according to previous meta-analyses and our analysis of studies that directly compared the prevalence of olfactory dysfunction between omicron and previous variants. The profile of the prevalence differences between ethnicities mirrors the results of a recent genome-wide association study that connected a gene locus encoding an odorant-metabolizing enzyme, UDP glycosyltransferase, to the extent of COVID-19-related loss of smell. Our analysis is consistent with the hypothesis that this enzyme contributes to the observed population differences.

Perspectives on the Pathophysiology, Management, and Relevance of Olfactory and Gustatory Dysfunction to COVID-19, Part One.

Context: Amelioration of olfactory and gustatory dysfunction (OGD) disorders has become a common requirement due to COVID-19. Although it's hardly exclusive to COVID-19, OGD's prevalence requires exploration of therapeutic and restorative modalities, on the broadest scale possible. No specific medication or treatment of any noteworthy efficacy exists for OGD. Objective: As Part 1 of a three-part article, a narrative review intended to examine the known causes of OGD, not restricted to COVID-19, and frame their relevance for development of new treatments or the repurposing of existing ones. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Results: Scientific investigation into mechanisms and treatment of OGD appears to be historically limited and unremarkable. Medical literature spanning decades reports a bleak clinical outlook with an abundance of speculation and hypotheses. Limited evidence of effective or reliable treatment exists, especially for chronic cases. Conclusions: With a dismal lack of medical support for a suddenly prevalent, but hardly novel set of maladies of taste and smell perception; the imperative for multifaceted and broad investigations across all medical disciplines is without question. Global urgency for the development of any treatment capable of reducing or resolving OGD triggered by COVID-19 is unprecedented. Part 2 of the current author's three-part series will address the details of current and past treatment approaches and clinical trials.

Drug-induced olfactory and gustatory dysfunction: Analysis of FDA adverse events reporting system.

OBJECTIVES: With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS). METHODS: The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell. RESULTS: From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs. CONCLUSION: Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology. LEVEL OF EVIDENCE: III.

Persistent post-COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium.

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell-mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post-COVID-19 smell loss.

Olfactory testing as COVID-19 screening in school children; A prospective cross-sectional study.

BACKGROUND: Little is known about olfactory changes in pediatric COVID-19. It is possible that children under-report chemosensory changes on questionnaires, similar to reports in adults. Here, we aim to describe COVID-19-related olfactory dysfunction in outpatient children. We hypothesized that children with COVID-19 will demonstrate abnormal olfaction on smell-identification testing at a higher rate than children with negative COVID-19 testing. METHODS: A prospective cross-sectional study was undertaken from June 2020-June 2021 at a tertiary care pediatric hospital. A consecutive sample of 205 outpatients aged 5-21 years undergoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) PCR testing were approached for this study. Patients with prior olfactory dysfunction were excluded. Participants were given a standard COVID-19 symptom questionnaire, a Smell Identification Test (SIT) and home-odorant-based testing within 2 weeks of COVID-19 testing. Prior to study enrollment, power calculation estimated 42 patients to determine difference in rates of SIT results between groups. Data were summarized with descriptive statistics. RESULTS: Fifty-one patients underwent smell identification testing (23 positive (45%) and 28 negative (55%) for COVID-19; mean age 12.7 years; 60% female). 92% of all patients denied subjective change in their sense of smell or taste but only 58.8% were normosmic on testing. There was no difference in screening questionnaires or SIT scores between COVID-19 positive and negative groups. CONCLUSIONS: Unlike adults, there was no statistical difference in olfactory function between outpatient COVID-19 positive and negative children. Our findings suggest a discrepancy between objective and patient-reported olfactory function in pediatric patients, and poor performance of current screening protocols at detecting pediatric COVID-19.