[Features of olfactory impairment connected with trigeminal nerve system]. / Osobennosti narusheniya obonyaniya v aspekte sistemy troinichnogo nerva.

Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.

Performance of a cost-effective olfactory test to evaluate hyposmia in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) causes motor and non-motor symptoms such as hyposmia, which is evaluated through olfactory tests in the clinical practice. OBJECTIVE: To assess the feasibility of using the modified Connecticut Chemosensory Clinical Research Center (mCCCRC) olfactory test and to compare its performance with the Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Germany) test. METHODS: A transversal case-control study in which the patients were divided into the PD group (PDG) and the control group (CG). The cost and difficulty in handling substances to produce the mCCCRC test kits were evaluated. Sociodemographic characteristics, smoking habits, past coronavirus disease 2019 (COVID-19) infections, self-perception of odor sense, and cognition through the Montreal Cognitive Assessment (MoCA) were also evaluated. The PDG was scored by part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and the Hoehn and Yahr Scale (H&Y) scale. Correlations were assessed through the Spearman rank correlation coefficient test (ρ, or rho). RESULTS: The mCCCRC test was easily manufactured and handled at a cost ten times lower compared with the SS-12. The groups (PDG: n = 34; CG: n = 38) were similar in terms of age, sex, level of schooling, smoking habits, and history of COVID-19. The tests results showed moderate correlation (rho = 0.65; p < 0.0001). The CG presented better cognitive performance and scored better in both tests (p < 0.0001). There was a tendency for a negative correlation with age, but good correlation with the MoCA (p = 0.0029). The results of the PDG group showed no correlation with olfactory results and motor performance or disease duration. The self-perception of hyposmia was low in both groups. CONCLUSION: The mCCCRC is an easy-to-apply and inexpensive method that demonstrated a similar performance to that of the SS-12 in evaluating olfaction in PD patients and healthy controls.

ANTECEDENTES: A doença de Parkinson (DP) cursa com sintomas motores e não motores como a hiposmia, que é avaliada por diferentes testes olfativos na prática clínica. OBJETIVO: Avaliar a viabilidade do teste olfatório Connecticut Chemosensory Clinical Research Center modificado (mCCCRC) e compará-la à do teste Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Alemanha). MéTODOS: Estudo transversal de caso-controle em que os pacientes foram divididos no grupo DP (GDP) e no grupo controle (GC). O custo e as dificuldades no manuseio das substâncias necessárias para a produção dos kits do teste mCCCRC foram avaliados. Características sociodemográficas, tabagismo, histórico de infecção por doença do coronavírus 2019 (coronavírus disease 2019, COVID-19, em inglês), autopercepção do olfato e cognição pelo Montreal Cognitive Assessment (MoCA) também foram avaliados. O GDP foi avaliado pela parte III da Unified Parkinson's Disease Rating Scale (UPDRS-III) e pela escala de Hoehn and Yahr (H&Y). As correlações utilizaram o teste do coeficiente de correlação de postos de Spearman (ρ, ou rho). RESULTADOS: O mCCCRC foi facilmente poroduzido e manipulado com custo dez vezes inferior ao do SS-12. Os grupos (GDP: n = 34; GC: n = 38) eram similares em termos de idade, sexo, escolaridade, tabagismo e histórico de COVID-19. Os resultados obtidos em ambos os testes mostraram excelente correlação (rho = 0.65; p < 0.0001). O GC teve um desempenho cognitivo melhor e pontuou melhor nos dois testes (p < 0.0001). Houve uma tendência a uma correlação negativa com a idade, mas boa correlação com a pontuação no MoCA (p = 0.0029). Os resultados olfativos do GDP não mostraram correlação com desempenho motor ou duração da doença. A autopercepção de hiposmia foi baixa em ambos os grupos. CONCLUSãO: O mCCCRC é um teste de fácil aplicação, baixo custo, e apresentou um desempenho semelhante ao do SS-12 na avaliação olfativa de pacientes com DP e controles saudáveis.

Longitudinal Exploration of Cortical Brain Activity in Cognitive Fog: An EEG Study in Patients with and without Anosmia.

BACKGROUND: Long-Covid, characterized by persistent symptoms following acute Covid-19 infection, represents a complex challenge for the scientific community. Among the most common and debilitating manifestations, cognitive fog is a neurological disorder characterized by mental confusion and cognitive difficulties. In this study, we investigated the long-term effects of previous Covid-19 infection on cortical brain activity in patients experiencing cognitive fog symptoms in the medium and long term. METHODS: A total of 40 subjects (20 females and 20 males) aged between 45 and 70 years (mean age (M) = 59.78, standard deviation (SD) = 12.93) participated in this study. This sample included individuals with symptoms of cognitive fog, both with and without anosmia, and a control group comprised of healthy subjects. All electroencephalography (EEG) data were collected in two sessions, 1 month and 8 months after recovery from Covid-19, to measure the neurophysiological parameters of P300 and beta band rhythms. RESULTS: The results revealed significant differences in the neurophysiological parameters of P300 and beta band rhythms in subjects affected by cognitive fog, and these alterations persist even 8 months after recovery from Covid-19. Interestingly, no significant differences were observed between the participants with anosmia and without anosmia associated with cognitive fog. CONCLUSIONS: These findings provide a significant contribution to understanding the long-term effects of Covid-19 on the brain and have important implications for future interventions aimed at managing and treating brain fog symptoms. The longitudinal assessment of cortical brain activity helps highlight the persistent impact of the virus on the neurological health of Long-Covid patients.

Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson's Disease Defined by REM-Sleep Behavior Disorder and Hyposmia.

Background: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added. Objective: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group. Methods: In this cross-sectional, case-control study, in a first set of analyses, we performed extensive cognitive testing on people with (n = 76) and a control group without (n = 195) probable RBD and hyposmia. Furthermore, we assessed motor and non-motor symptoms related to Parkinson's Disease (PD). After propensity score matching, we compared 62 P-PD with 62 age- and sex-matched controls. In addition, we performed regression analyses on the total sample (n = 271). In a second set of analyses, we used, a.o., the CUPRO to evaluate retrograde procedural memory and visuo-constructive functions. Results: People with P-PD showed significantly poorer performances in global cognition, visuo-constructive and executive functions, mainly in mental flexibility (p < 0.001; p = 0.004; p = 0.003), despite similar educational levels (p = 0.415). We observed significantly more motor and non-motor symptoms (p < 0.001; p = 0.004), higher scores for depression (p = 0.004) and apathy (p < 0.001) as well as lower quality of life (p < 0.001) in P-PD. CONCLUSIONS: Our findings confirm that global cognitive, executive, and visuo-constructive deficits define the P-PD group. In addition, depression, apathy, and lower quality of life were more prevalent in P-PD. If replicated in other samples, executive and visuo-constructive deficits should be considered in non-motor P-PD. Determining specific patterns will support early recognition of PD, secondary prevention of complications and the development of neuroprotective treatments.

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

Longitudinal brain changes in Parkinson's disease with severe olfactory deficit.

INTRODUCTION: Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD. METHODS: Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis. RESULTS: Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus. CONCLUSIONS: The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.

Headache as a Symptom of COVID-19: Narrative Review of 1-Year Research.

PURPOSE OF REVIEW: Headache is a common symptom of COVID-19 with emerging literature being published on the subject. Although it may seem unspecific, scientific evidence has allowed a better definition of this headache type, revealing relevant associations with other COVID-19 symptoms and prognoses. We therefore sought to highlight the most remarkable findings concerning headache secondary to COVID-19, specifically focusing on epidemiology, characteristics, pathophysiology, and treatments. RECENT FINDINGS: The real prevalence of headache as a symptom of COVID-19 is still unclear ranging from 10 to 70%. Headache mainly has a tension-type-like phenotype, although 25% of individuals present with migraine-like features that also occur in patients without personal migraine history. This finding suggests that a likely pathophysiological mechanism is the activation of the trigeminovascular system. SARS-CoV-2 neurotropism can occur by trans-synaptic invasion through the olfactory route from the nasal cavity, leading to anosmia which has been associated with headache. SARS-CoV-2 protein has been found not only in olfactory mucosa and bulbs but also in trigeminal branches and the trigeminal ganglion, supporting this hypothesis. However, other mechanisms such as brain vessels inflammation due to SARS-CoV-2 damage to the endothelium or systemic inflammation in the context of cytokine storm cannot be ruled out. Interestingly, headache has been associated with lower COVID-19 mortality. No specific treatment for COVID-19 headache is available at present. Studies show that investigating COVID-19 headache represents an opportunity not only to better understand COVID-19 in general but also to advance in the knowledge of both secondary and primary headaches. Future research is therefore warranted.

COVID-19 Anosmia: High Prevalence, Plural Neuropathogenic Mechanisms, and Scarce Neurotropism of SARS-CoV-2?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 2019 (COVID-19). It is known as a respiratory virus, but SARS-CoV-2 appears equally, or even more, infectious for the olfactory epithelium (OE) than for the respiratory epithelium in the nasal cavity. In light of the small area of the OE relative to the respiratory epithelium, the high prevalence of olfactory dysfunctions (ODs) in COVID-19 has been bewildering and has attracted much attention. This review aims to first examine the cytological and molecular biological characteristics of the OE, especially the microvillous apical surfaces of sustentacular cells and the abundant SARS-CoV-2 receptor molecules thereof, that may underlie the high susceptibility of this neuroepithelium to SARS-CoV-2 infection and damages. The possibility of SARS-CoV-2 neurotropism, or the lack of it, is then analyzed with regard to the expression of the receptor (angiotensin-converting enzyme 2) or priming protease (transmembrane serine protease 2), and cellular targets of infection. Neuropathology of COVID-19 in the OE, olfactory bulb, and other related neural structures are also reviewed. Toward the end, we present our perspectives regarding possible mechanisms of SARS-CoV-2 neuropathogenesis and ODs, in the absence of substantial viral infection of neurons. Plausible causes for persistent ODs in some COVID-19 convalescents are also examined.

Integrating pheromonal and spatial information in the amygdalo-hippocampal network.

Vomeronasal information is critical in mice for territorial behavior. Consequently, learning the territorial spatial structure should incorporate the vomeronasal signals indicating individual identity into the hippocampal cognitive map. In this work we show in mice that navigating a virtual environment induces synchronic activity, with causality in both directionalities, between the vomeronasal amygdala and the dorsal CA1 of the hippocampus in the theta frequency range. The detection of urine stimuli induces synaptic plasticity in the vomeronasal pathway and the dorsal hippocampus, even in animals with experimentally induced anosmia. In the dorsal hippocampus, this plasticity is associated with the overexpression of pAKT and pGSK3ß. An amygdalo-entorhino-hippocampal circuit likely underlies this effect of pheromonal information on hippocampal learning. This circuit likely constitutes the neural substrate of territorial behavior in mice, and it allows the integration of social and spatial information.

Altered smell and taste: Anosmia, parosmia and the impact of long Covid-19.

BACKGROUND: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell. METHODS: We conducted exploratory thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020. RESULTS: Participants reported difficulty explaining and managing an altered sense of taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others. CONCLUSIONS: Our findings suggest altered taste and smell with Covid-19 may lead to severe disruption to daily living that impacts on psychological well-being, physical health, relationships and sense of self. More specifically, participants reported impacts that related to reduced desire and ability to eat and prepare food; weight gain, weight loss and nutritional insufficiency; emotional wellbeing; professional practice; intimacy and social bonding; and the disruption of people's sense of reality and themselves. Our findings should inform further research and suggest areas for the training, assessment and treatment practices of health care professionals working with long Covid.

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Acquired olfactory loss alters functional connectivity and morphology.

Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies assessing sensory-dependent plasticity have focused on effects from either early onset or long-term sensory loss and little is known how the recent sensory loss affects the human brain. With the aim of determining how recent sensory loss affects cerebral morphology and functional connectivity, we assessed differences between individuals with acquired olfactory loss (duration 7-36 months) and matched healthy controls in their grey matter volume, using multivariate pattern analyses, and functional connectivity, using dynamic connectivity analyses, within and from the olfactory cortex. Our results demonstrate that acquired olfactory loss is associated with altered grey matter volume in, among others, posterior piriform cortex, a core olfactory processing area, as well as the inferior frontal gyrus and angular gyrus. In addition, compared to controls, individuals with acquired anosmia displayed significantly stronger dynamic functional connectivity from the posterior piriform cortex to, among others, the angular gyrus, a known multisensory integration area. When assessing differences in dynamic functional connectivity from the angular gyrus, individuals with acquired anosmia had stronger connectivity from the angular gyrus to areas primary responsible for basic visual processing. These results demonstrate that recently acquired sensory loss is associated with both changed cerebral morphology within core olfactory areas and increase dynamic functional connectivity from olfactory cortex to cerebral areas processing multisensory integration.

Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent's nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.

Is loss of smell an early predictor of COVID-19 severity: a systematic review and meta-analysis.

Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease.

Clinical relevance of SARS-CoV-2 infection in late pregnancy.

BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.