Real-time monitoring of respiratory health is increasingly critical, particularly in addressing global health challenges such as Corona Virus Disease 2019 (COVID-19). Smart masks equipped with biosensing mechanisms revolutionize respiratory health monitoring by enabling real-time detection of respiratory parameters and biomarkers. In recent years, significant advancements have been achieved in the development of smart masks based on different sensor types with high sensitivity and accuracy, flexible functionality, and portability, providing new approaches for remote and real-time monitoring of respiratory parameters and biomarkers. In this review, we aim to provide a comprehensive overview of the current state of development and future potential of biosensing smart masks in various domains. This review outlines a systematic categorization of smart masks according to diverse sensing principles, classifying them into six categories: electrochemical sensors, optical sensors, piezoelectric sensors, and others. This review discusses the basic sensing principles and mechanisms of smart masks and describes the existing research developments of their different biosensors. Additionally, it explores the innovative applications of smart masks in health monitoring, protective functions, and expanding application scenarios. This review also identifies the current challenges faced by smart masks, including issues with sensor accuracy, environmental interference, and the need for better integration of multifunctional features. Proposed solutions to these challenges are discussed, along with the anticipated role of smart masks in early disease detection, personalized medicine, and environmental protection.

Olfactory dysfunction is one of the most prevalent diseases in otorhinolaryngology, particularly since the coronavirus 2019 (COVID-19) pandemic, with a potential impact on daily life. Several etiological factors can contribute to olfactory dysfunction owing to the complexity and specificity of the olfactory transmission pathway. However, current treatments for olfactory dysfunction are limited and their efficacy is unsatisfactory. Olfactory stem cells are multifunctional stem cells in the olfactory mucosa that comprise both horizontal and global basal stem cells (HBCs and GBCs, respectively). These cells can differentiate into various cell types in response to different stimuli with distinct characteristics. The aim of the study was to discuss the mechanisms and functions of stem cells and their application in the treatment of olfactory dysfunction.

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely related to SARS-CoV and uses angiotensin-converting enzyme 2 as its cellular receptor. In early 2020, reports emerged linking CoV disease 2019 (COVID-19) to olfactory and gustatory disturbances. These disturbances could be attributed to virus-induced damage to olfactory neurons or immune responses, thereby affecting sensory functions. This randomized controlled trial aimed to evaluate the effectiveness of a structured orofacial rehabilitation program in improving smell (olfaction) and taste (gustation) sensations in children post-COVID-19. Methods: Forty children recovering from COVID-19 in government hospitals in Saudi Arabia were included and randomly assigned to the control group or the experimental group. The orofacial program included (a) facilitation of olfactory function using the 40-item modified Arabic version of the University of Pennsylvania Smell Identification Test (UPSIT); (b) assessment of gustatory function using taste strips with four varying concentrations; and (c) orofacial myofunctional therapy. The intervention was applied three times a week and lasted for 3 months. Results: The experimental group showed a significantly greater improvement in UPSIT scores (median change of 24.1%) than the control group (14.7%; p = 0.010). However, no significant difference was found in the taste strip test scores among the groups or between male and female participants. Conclusions: This study suggests that a structured orofacial rehabilitation program could enhance olfactory and gustatory functions in children recovering from COVID-19.

Following the Coronavirus Disease 2019 (COVID-19) pandemic, many patients have reported ongoing smell and taste issues. This study aims to investigate the prevalence of olfactory and gustatory dysfunction among patients with a history of COVID-19 and its association with autonomic dysfunction and disability.

This case-control study included a COVID-19 group (n = 82) and a control group (n = 82). Olfactory dysfunction, including parosmia and taste problems, was explored using self-reports and the Quick Smell Identification Test (QSIT). The association between post-COVID-19 disability severity and taste and smell alterations was also analyzed. Moreover, autonomic function was evaluated using the Composite Autonomic Symptom Scale-31 (COMPASS-31) to assess the association between autonomic and olfactory dysfunction.

Significantly higher rates of ongoing smell (26.8%) and taste (14.6%) dysfunction were reported for the post-COVID-19 group compared to the control group. Post-COVID-19 patients reported 36.6 times more smell issues and 8.22 times more taste issues than controls. Parosmia scores were significantly worse in the post-COVID-19 group, while QSIT scores showed no significant difference between the groups. However, those with worse QSIT scores exhibited significantly more ongoing smell issues. No significant association was observed between disability and altered smell or taste. Higher secretomotor dysfunction scores were significantly associated with abnormal QSIT scores and worse parosmia scores; the other domains of the COMPASS-31 scale showed no significant associations.

The findings indicated a potential link between autonomic and olfactory dysfunction. Further studies are needed to elucidate the mechanisms underlying persistent olfactory and autonomic dysfunction in post-COVID-19 patients.

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.

Atypical parkinsonisms (APs) present various symptoms including motor impairment, cognitive decline, and autonomic dysfunction. Olfactory loss (OL), being a significant non-motor symptom, has emerged as an under-evaluated, yet potentially valuable, feature that might aid in the differential diagnosis of APs.

The most pronounced OL is usually associated with Dementia with Lewy Bodies (DLB). While the view about the normosmic course of Multiple System Atrophy (MSA) remains unchanged, research indicates that mild OL may occur in a subset of patients with Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). This might be linked to the deposition of abnormal protein aggregates in the central nervous system.

The aim of this review is to discuss the role of OL and its degree and pattern in the pathogenesis and course of APs. Olfactory testing could serve as a non-invasive, quick screening tool to differentiate between APs and project disease progression.

There is a need for further evaluation of this topic. This may lead to the development of standardized olfactory testing protocols that could be implemented in clinical practice, making differential diagnosis of APs more convenient. Understanding differences in the sense of smell could create an avenue for more targeted therapeutic strategies.

Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests.

In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT.

Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up.

A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction.

Exposure to occupational metallic mixtures has a potential impact on olfactory function. However, research evidence is limited on the potential impact of exposure to metallic mixtures and olfactory dysfunction. Furthermore, the coal dust generated contains multiple various metals during coal mining, and no study yet has focus on the olfactory dysfunction of coal miners.

In this study, we evaluate the association between urinary metallic mixtures and olfactory function in coal miners, while also exploring the potential applicability of plasma olfactory marker protein (OMP) as a biomarker for assessing olfaction.

From July to October 2023, coal workers from seven different coal mining enterprises were recruited for the survey when they come for the employee health checkup. Ultimately, 376 participants were met the inclusion criteria and, respectively, determined with the concentrations of urine (16 metals) and plasma (OMP). Meanwhile, applying UPSIT to access their olfactory function. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with olfactory function. Bayesian kernel machine regression (BKMR) and Quantile g-computation (QG-C) regression were employed to assess the overall association between metal mixtures and olfactory function and identify the major contributing elements.

In a single-metal model, two metals in urine were found to be significantly associated with olfactory function. RCS analysis further revealed that the association between Iron (Fe) and olfactory function was linear, while Lead (Pb) exhibited a non-linear. The BKMR model demonstrated a significant positive association between metal mixture concentration and olfactory function. Combined QG-C regression analysis suggested that metals Cr, Fe, Se, Sb, and Pb could impact the performance of the olfactory test (UPSIT), with Pb being identified as the most influential contributor. The correlation between plasma OMP protein levels and urinary metal concentrations was weak.

Multiple metals are associated with olfactory function in the coal miners. A significant positive association was observed between metal mixture concentrations and olfactory function, with Pb being the most important contributor. In this study, plasma OMP has not been demonstrated to serve as a biomarker for olfactory function.

The actual role of coronavirus disease 2019 (COVID-19) in brain damage has been increasingly reported, necessitating a meta-analysis to collate and summarize the inconsistent findings from functional imaging and voxel-based morphometry (VBM) studies. A comprehensive voxel-wise meta-analysis of the whole brain was conducted to identify alterations in functional activity and gray matter volume (GMV) between COVID-19 patients and healthy controls (HCs) by using Seed-based d Mapping software. We included 15 functional imaging studies (484 patients with COVID-19, 534 HCs) and 9 VBM studies (449 patients with COVID-19, 388 HCs) in the analysis. Overall, patients with COVID-19 exhibited decreased functional activity in the right superior temporal gyrus (STG) (extending to the right middle and inferior temporal gyrus, insula, and temporal pole [TP]), left insula, right orbitofrontal cortex (OFC) (extending to the right olfactory cortex), and left cerebellum compared to HCs. For VBM, patients with COVID-19, relative to HCs, showed decreased GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (extending to the bilateral OFC), and left cerebellum, and increased GMV in the bilateral amygdala (extending to the bilateral hippocampus, STG, TP, MTG, and right striatum). Moreover, overlapping analysis revealed that patients with COVID-19 exhibited both decreased functional activity and increased GMV in the right TP (extending to the right STG). The multimodal meta-analysis suggests that brain changes of function and structure in the temporal lobe, OFC and cerebellum, and functional or structural alterations in the insula and the limbic system in COVID-19. These findings contribute to a better understanding of the pathophysiology of brain alterations in COVID-19. SIGNIFICANCE STATEMENT: This first large-scale multimodal meta-analysis collates existing neuroimaging studies and provides voxel-wise functional and structural whole-brain abnormalities in COVID-19. Findings of this meta-analysis provide valuable insights into the dynamic brain changes (from infection to recovery) and offer further explanations for the pathophysiological basis of brain alterations in COVID-19.

This study aimed to evaluate recovery patterns of olfactory dysfunction among recovered COVID-19 patients, both subjective and objective, and correlate this recovery to the severity of the disease.

The study recruited 200 patients and assigned them to two equal groups, one of them was a control group. The olfactory function of the study group was assessed via subjective and objective methods at baseline and then monthly for three months, with changes in smell function reported at each visit. These patients underwent chemosensory testing using the Sniffin' Sticks test and completed the validated Arabic version of the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS).

Olfactory dysfunction occurred on the first day of COVID-19 symptoms in 37% of participants. Subjective reports suggested smell recovery in 55% after 3 months, but Sniffin' Sticks showed only 1% with normal function, indicating persistent deficits in others. This study revealed smell recovery for 93% of participants (median 14 days), with most (58%) recovering within 2 weeks. No significant links were found between demographics, COVID-smell loss timing, and recovery speed.

Three months after COVID-19, many patients perceive smell recovery, but objective tests reveal shockingly high rates of persistent dysfunction. Further follow-up with objective tests is vital to assess the true burden and potential long-term effects of smell loss.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19's impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease's neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies.

Angiotensin-converting enzyme 2 (ACE2) is the main molecular target for coronavirus SARS-CoV-2 to enter cells. Molecularly specific tracers that bind to ACE2 with high affinity can be used to determine the tissue distribution of this important receptor, noninvasively. A novel targeting PET imaging probe, [18F]AlF-DX600-BCH, was developed to detect the in vivo expression of ACE2 and monitor response to therapy. Preclinical experiments, including biodistribution, PET imaging, and tissue section analysis, were conducted after tests of in vitro and in vivo stability and pharmacokinetics. The agent was advanced to clinical evaluation in 10 volunteers who received [18F]AlF-DX600-BCH PET/CT at 1 and 2 h after injection (NCT04542863). Preclinical results of both biodistribution and PET demonstrated [18F]AlF-DX600-BCH accumulation in rat kidney (standardized uptake value; SUVkidney/normal > 50), along with specific uptake in testes (SUVtestis/normal > 10) tissues. Kidney, gastrointestinal, and bronchial cell labeling were correlated to ACE2 positive by immunohistochemistry (IHC) staining. In clinical imaging, significant tracer accumulation was predominantly observed in the urinary and reproductive system (SUVrenal cortex = 32.00, SUVtestis = 4.56), and the conjunctiva and nasal mucosa saw elevated uptake in several cases. This work is the first report of a radioisotope probe, [18F]AlF-DX600-BCH, targeting ACE2 with promising preliminary preclinical and translational outlook, thereby demonstrating the potential of noninvasive mapping of ACE2.

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Olfactory and gustatory dysfunctions (OGDs) are key symptoms of coronavirus disease 2019 (COVID-19), which may lead to neurological complications, and lack of effective treatment. This may be because post-disease treatments may be too late to protect the olfactory and gustatory functions.

To evaluate the effectiveness of early use of saline nasal irrigation (SNI), corticosteroid nasal spray, and saline or chlorhexidine gluconate mouthwash for preventing OGDs in COVID-19.

This study was a double-blind randomized controlled trial.

The study was conducted from 5 May to 16 June 2022. We recruited patients from three hospitals who were admitted with COVID-19 but without OGDs on the day of admission. Olfactory and gustatory functions were evaluated using the Taste and Smell Survey and the numerical visual analog scale. Participants were randomized to the saline, drug or control groups. The control group received no intervention, saline group received SNI plus saline nasal spray and mouthwash, and the trial group received SNI plus budesonide nasal spray and chlorhexidine gluconate mouthwash. Participants were assessed again on the day of discharge.

A total of 379 patients completed the trial. The prevalence of OGDs was significantly lower in the saline (11.8%, 95% CI, 6.6-19.0%; P < 0.001) and drug (8.3%, 95% CI, 4.1-14.8%; P < 0.001) groups than in the control group (40.0%, 95% CI, 31.8-48.6%). Additionally, both interventions reduced the severity of OGDs.

We demonstrated effective strategies for preventing COVID-19-related OGDs, and the findings may guide early management of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection to reduce the incidence of COVID-19-related complications.

This study aimed to examine the olfactory and gustatory dysfunctions (OGDs) among hospitalized patients with a novel strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), lineage B.1.617.2, also known as the delta variant, in Xi'an, China through verbal interviews.

Clinical information of 370 hospitalized patients infected with the delta variant in the Aerospace City Branch of Xi'an People's Hospital in Xi'an, China from December 27, 2021 to January 10, 2022 were collected. The prevalence and characteristics of OGDs were collected using a simple questionnaire submitted to all infected patients, including questions about the presence and absence of OGDs.

Among the 370 patients infected with the delta variant, 28 (7.6%) reported OGDs. A significant proportion of patients with self-reported OGDs were younger than those without (28.9 ± 10.5 vs. 35.3 ± 13.9, P = 0.005) and had significantly higher rates of sore throat and rhinitis (28.6% vs. 12.3%, P = 0.033; 42.9% vs. 9.9%, P = 0.000). Women were significantly more affected by OGDs than men (67.9% vs. 32.1%, P = 0.012). Vaccinated and unvaccinated delta variant-infected patients showed statistically significant differences in terms of disease severity (P = 0.002).

The prevalence of OGDs in the delta variant infection was lower than that in wild-type SARS-CoV-2 infection. Meanwhile, young age, female sex, and upper respiratory tract symptoms could be closely related to the occurrence of OGDs in the delta variant infection. In addition, a satisfactory level of efficacy was obtained with coronavirus disease 2019 vaccines against moderate and severe delta variant infections.

Olfactory dysfunction has been included among the early symptoms of coronavirus disease (COVID-19). Evidence suggests that a relationship exists between the duration of olfaction disorders and the probability of developing severe COVID-19. Given the scope of the COVID-19 pandemic, this study aimed to determine the frequency of smell alteration and its association with the severity of COVID-19 in a referral hospital in Peru, which is one of the most affected countries in the Latin American region.

This study was an observational, prospective cohort study that included patients with COVID-19 who were treated at the Hospital Nacional Edgardo Rebagliati Martins from August to November 2020. To assess the association, the chi-square test of independence or Fisher's exact test was performed. The outcome variable was COVID-19 severity, and the exposure variable was olfactory dysfunction. The first data collection was in the emergency department and the follow-up was via telephone.

A total of 179 patients were included. The mean age was 61.6 ± 15.5 years, and 129 patients (72.1%) were male. Olfactory dysfunction was observed in 43 patients (24%). An inverse association was found between age and olfactory dysfunction (P = .002). No significant association was found between COVID-19 severity level and olfactory alteration (P = .056). However, a direct association was found between COVID-19 severity and age (P = .003), cough (P < .001), and respiratory distress (P = .003).

This study did not find any association between the severity of COVID-19 and olfactory dysfunction. It showed a low incidence rate of smell alteration compared with studies from other regions. Moreover, smell alteration was associated with younger age.

Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.

We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.

Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004).

OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Olfactory dysfunction is one of the most recognized symptoms of COVID-19, significantly impacting quality of life, particularly in cases where recovery is prolonged. This review aims to explore patterns of olfactory recovery post-COVID-19 infection, with particular focus on delayed recovery.

Published literature in the English language, including senior author's own work, online and social media platforms, and patients' anecdotal reports.

A comprehensive review of the literature was undertaken by the authors with guidance from the senior author with expertise in the field of olfaction.

Based on self-report, an estimated 95% of patients recover their olfactory function within 6 months post-COVID-19 infection. However, psychophysical testing detects higher rates of persistent olfactory dysfunction. Recovery has been found to continue for at least 2 years postinfection; negative prognostic indicators include severe olfactory loss in the acute phase, female sex, and older age. Variability in quantitative and qualitative disturbance in prolonged cases likely reflects both peripheral and central pathophysiological mechanisms. Limitations of many of the reviewed studies reflect lack of psychophysical testing and baseline olfactory assessment.

Post-COVID-19 olfactory dysfunction remains a significant health and psychosocial burden. Emerging evidence is improving awareness and knowledge among clinicians to better support patients through their olfactory rehabilitation, with hope of recovery after several months or years. Further research is needed to better understand the underlying pathogenesis of delayed recovery, identify at risk individuals earlier in the disease course, and develop therapeutic targets.

The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on self-reported alterations in taste and/or smell function.

Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019 (post-COVID-19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure-self-reported total recovery of chemosensory symptoms-was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc).

The median time between COVID-19 symptom onset and the interviews was 81 days (interquartile range: 60-104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery. Those who took oral zinc were less likely to improve.

No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

Accurate identification of cancer stages is challenging due to the complexity and heterogeneity of the disease. Current clinical diagnosis methods primarily rely on phenotypic observations, which may not capture early molecular-level changes accurately.

In this study, a novel biomarker recognition method was proposed tailored for cancer stages by considering the change of gene expression relationships. Utilizing the sample-specific information and protein-protein interaction networks, the group specific networks were constructed to address the limited specificity of potential biomarkers. Then, a specific feature recognition method was proposed based on these group specific networks, which employed the random forest algorithm for initial screening followed by a recursive feature elimination process to identify the optimal biomarker subset. During exploring optimal results, a strategy termed the Cost-Benefit Ratio, was devised to facilitate the identification of stage-specific biomarkers.

Comparative experiments were conducted on lung adenocarcinoma and breast cancer datasets to validate the method's efficacy and generalizability. The results showed that the identified biomarkers were highly stage-specific, and the F1 scores for predicting cancer stages were significantly improved. For the lung adenocarcinoma dataset, the F1 score reached 97.68%, and for the breast cancer dataset, it achieved 96.87%. These results significantly surpassed those of three conventional methods in terms of F1 scores. Moreover, from the perspective of biological functions, the biomarkers were proved playing an important role in cancer stage-evolution.

The proposed method demonstrated its effectiveness in identifying stage-related biomarkers. By using these biomarkers as features, accurate prediction of cancer stages was achieved. Furthermore, the method exhibited potential for biomarker identification in subtype analyses, offering novel perspectives for cancer prognosis.

Sudden onset of olfactory dysfunction (OD) manifesting as hyposmia and/or anosmia occurred in many COVID-19 patients, with a frequency as high as 85.6%. Given the morbidity and mortality of COVID-19, it is important to recognize the symptoms early so that the infected person can be diagnosed, isolated and treated early. Hence, this study was undertaken to know the prevalence of Sino-nasal symptoms with special reference to olfactory dysfunction in COVID-19 patients.

It is a cross sectional observational study involving 160 COVID-19 patients aged 18 to 100 years selected by universal sampling. OD was analyzed and compared with various inflammatory markers and Sino-nasal symptoms. Patients were followed up until their discharge from the hospital or until death due to COVID-19 related health issues.

Out of 160 subjects included in the study, 61.88 % of the study participants were males and 38.13% were females. The mean age was 44.50 ± 16.43 years. A total of 51 patients (31.87%) developed OD. Fifty one (31.87%) patients developed OD (anosmia/hyposmia). Among the individuals with anosmia/hyposmia, majority of patients (n=26) (50.98%) complained of more than 75% loss of smell sensation. Mean duration of anosmia/hyposmia was 9.92 ± 3.71 days. OD correlated with serum ferritin levels (p=0.0453).

Anosmia/hyposmia was found in significant proportion of patients with covid-19 which correlated with the disease severity and serum ferritin levels and hence can serve as surrogate marker of disease severity.

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 revealed a huge number of problems as well as discoveries in medicine, notably, regarding the effects of the virus on the central nervous system (CNS) and peripheral nervous system (PNS). This paper is a narrative review that takes a deep dive into the complex interactions between COVID-19 and the NS. Therefore, this paper explains the broad range of neurological manifestations and neurodegenerative diseases caused by the virus. It carefully considers the routes through which SARS-CoV-2 reaches the NS, including the olfactory system and of course, the hematogenous route, which are also covered when discussing the virus's direct and indirect mechanisms of neuropathogenesis. Besides neurological pathologies such as stroke, encephalitis, Guillain-Barré syndrome, Parkinson's disease, and multiple sclerosis, the focus area is also given to the challenges of making diagnosis, treatment, and management of these conditions during the pandemic. The review also examines the strategic and interventional approaches utilized to prevent these disorders, as well as the ACE2 receptors implicated in the mediation of neurological effects caused by COVID-19. This detailed overview, which combines research outputs with case data, is directed at tackling this pandemic challenge, with a view toward better patient care and outcomes in the future.

Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron.

This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included. These children were allocated into the PSNI group and the control group. The primary outcome was the duration of viral shedding (DVS), and the secondary outcome was the change in clinical symptoms.

The median age of all participants was 5.59 (6.26) years old. The DVS was significantly shorter in the PSNI group [2.40 (1.13)] than in the control group [3.09 (2.14)] (P = 0.014). The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.04-1.55; P = 0.017]. Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group. The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group, but there was no evidence showing that PSNI contributes to the benefit compared with the control group.

PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting.

The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test).

Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting.

We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41.

These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction.

Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset.

A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets.

The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample.

Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms.

Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone.

These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.

The aim of the study was to analyze objective and subjective olfactory/gustatory function in post-COVID-19 infection (PCI).

Patients with past PCR-confirmed COVID-19 infection and persistent olfactory/gustatory complaints were investigated. Olfactory threshold and identification, gustatory detection, identification, and magnitude scaling were tested.

A total of 42 PCI subjects were compared to 41 age- and gender-matched controls with no COVID-19 history. All PCI tested had mild COVID-19 disease. Mean interval between COVID-19 confirmations to testing was 7.4 ± 3.1 months. PCI subjects complained of combined dysfunction in 85.7%, isolated olfactory or gustatory dysfunction in 7.1% each. Combined complaints were significantly higher in PCI (p < 0.001). Objective testing showed significantly higher prevalence of dysfunction in PCI versus controls for hyposmia (73.8%, 12.2%), anosmia (11.9%, 0%), odor identification (68.5%, 83.0%), hypogeusia (23% and 2.4%, respectively), and impaired magnitude scaling, (p < 0.05). All PCI subjects with hypogeusia had abnormal gustatory magnitude scaling.

While most PCI subjects complained of combined gustatory and olfactory dysfunction, objective testing showed in the majority an isolated single sense dysfunction, with a low level of agreement between subjective and objective findings. Abnormal objective results for all olfactory and gustatory functions tested may suggest a central rather than peripheral mechanism, although concomitant mechanisms cannot be excluded.

Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes. This cell-cell communication is necessary to coordinate the immune response to lower respiratory tract infection. Recent discoveries identify an important role for the microtubule-associated protein tau that is expressed in lung capillary endothelia in the host-pathogen interaction. This endothelial tau stabilizes microtubules necessary for barrier integrity, yet infection drives production of cytotoxic tau variants that are released into the airways and circulation, where they contribute to end-organ dysfunction. Similarly, beta-amyloid is produced during infection. Beta-amyloid has antimicrobial activity, but during infection it can acquire cytotoxic activity that is deleterious to the host. The production and function of these cytotoxic tau and amyloid variants are the subject of this review. Lung-derived cytotoxic tau and amyloid variants are a recently discovered mechanism of end-organ dysfunction, including neurocognitive dysfunction, during and in the aftermath of infection.

Background Anosmia has been identified as a distinctive symptom of COVID-19, leading to hypotheses about its pathophysiological underpinnings, including the potential role of paranasal sinus mucosal thickening. Objective To investigate the association between paranasal sinus mucosal thickening and anosmia in COVID-19 patients, providing insights into the complex clinical manifestations of the disease. Methods This retrospective cohort study analyzed CT paranasal sinus from 270 confirmed COVID-19 patients, divided into those with anosmia (n = 23, 8.52%) and those without anosmia (n = 247, 91.48%). Statistical analysis, including independent t-tests, was employed to compare mucosal thickening between the groups. Results The study found an average mucosal thickening of 0.03 in patients with anosmia and 0.02 in those without, with no statistically significant difference between the groups (p = 0.480, which is greater than 0.05). The findings suggest that mucosal thickening in the paranasal sinuses does not serve as a definitive correlate of anosmia among COVID-19 patients. Conclusion The absence of a significant correlation between paranasal sinus mucosal thickening and anosmia in COVID-19 patients indicates that the pathophysiology of anosmia may involve factors beyond anatomical changes, including direct viral effects and systemic inflammatory responses.

Objective: The aim of this study is to evaluate local and systemic photobiomodulation (PBM) in patients with COVID-19-related dysgeusia, with the expectation of improving taste dysfunction. Background: PBM has garnered attention as a potential therapy in long COVID, a condition characterized by many persistent symptoms following the acute phase of COVID-19. Among these symptoms, dysgeusia, or altered taste perception, can significantly affect patients' quality of life. Emerging research suggests that PBM may hold promise in ameliorating dysgeusia by modulating cellular processes and reducing inflammation. Further clinical studies and randomized controlled trials are essential to establish the efficacy and safety of PBM for the treatment of dysgeusia in long COVID, but initial evidence suggests that this noninvasive modality may offer a novel avenue for symptom management. Methods: Seventy patients experiencing dysgeusia were randomly assigned to receive active local and systemic PBM (n = 34) or simulated PBM (n = 36). Low-power laser (red wavelength) was used at 18 spots on the lateral borders of the tongue (3 J per spot), salivary glands (parotid, sublingual, and submandibular glands-3 J per spot), and over the carotid artery for 10 min (60 J). Alongside laser therapy, all patients in both groups received weekly olfactory therapy for up to 8 weeks. Results: Dysgeusia improved in both groups. At weeks 7 and 8, improvement scores were significantly higher in the PBM group than in the sham group (p = 0.048). Conclusions: Combined local and systemic PBM, as applied in this study, proved effective and could serve as a viable treatment option for alleviating dysgeusia in long-COVID patients. Clinical Trial Registration: RBR-2mfbkkk.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

Olfactory disorders have a significant impact on patients' quality of life but are often underestimated in clinical practice. Upper respiratory tract infections (URTIs) are a common cause of olfactory loss. While most cases of olfactory loss due to URTIs are conductive and reversible, post-viral olfactory dysfunction (PVOD) persists despite symptom improvement. PVOD is attributed to damage to the olfactory epithelium and nerves or central olfactory pathway lesions. The Alcohol Sniff Test (AST) has been proposed as a tool to assess olfactory function in the acute phase and aid in differentiating PVOD from conductive disorders. This study aims to evaluate the effectiveness of the AST as a predictor of post-viral olfactory loss in patients with flu-like syndrome. An observational cross-sectional study was conducted among employees with flu-like syndrome at a tertiary hospital. Three groups were formed: flu-like syndrome with conductive disorder without COVID-19 (PVOD-), flu-like syndrome with neurosensory and/or central disorder due to COVID-19 (PVOD +), and an asymptomatic control group. The Alcohol Sniff Test was performed to assess olfactory function. Statistical analysis was conducted to evaluate the AST's performance. For a cut off of 10 cm, 88.57% of PVOD + patients and 60.53% of PVOD - patients showed AST alteration, respectively (p = 0.013, OR = 5.05, 95% CI [1.48-17.25]). There was a statistically significant difference in the mean distance between the PVOD + group (4.35 ± 4.1 cm) and the control group (20 ± 4.33 cm) (p < 0.05). This relationship was also observed between the PVOD + and PVOD- groups (9 cm ± 7.5) (p < 0.05) and between the PVOD- and control groups (p < 0.05). For a cut off of 10 cm, the AST showed a sensitivity of 88% and specificity of 41%, resulting in an Odds Ratio of 9.7 (95% CI 3.3-28.1) (p < 0.001) and a Positive Predictive Value of 69.4% for PVOD. PVOD, including cases associated with COVID-19, is a prevalent cause of olfactory loss. The Alcohol Sniff Test demonstrated promising results in identifying PVOD in patients with flu-like syndrome. The test's simplicity and accessibility make it a valuable tool for early screening and identifying individuals who may benefit from prompt treatment. The Alcohol Sniff Test (AST) shows potential as an effective tool for screening post-viral olfactory loss in patients with flu-like syndrome. It can aid in early identification of PVOD cases and facilitate timely interventions to reduce the likelihood of persistent hyposmia.

The COVID-19 pandemic is a real global health crisis. Its clinical presentation has evolved over time with an increasing number of symptoms. Olfactory dysfunction (OD) has recently been recognized as a frequent symptom relevant to screening for COVID-19, especially in pauci-asymptomatic forms. However, the underlying mechanisms of OD are not yet fully understood.

To determine the prevalence of OD in healthcare workers with SARS-CoV-2 and to identify its associated factors.

This is a cross-sectional, analytical study, carried out during a period of six months and including all healthcare workers at Farhat Hached Academic Hospital (Tunisia) who were diagnosed with SARS-CoV-2 by PCR, RAT, or chest CT scan.

A total of 474 healthcare workers were included, representing a participation rate of 85.4%. The mean age was 41.02±10.67 years with a sex ratio of 0.2. The distribution of this population by department noted that it was mainly maternity (13.9%). The most presented workstation was nursing (31.4%). OD represented 39.2% of the reasons for consultation. Hospitalization was indicated in 16 patients (3.4%). The average duration of hospitalization was 8.87 ± 7.8 days. The average time off work was 17.04 ± 11.6 days. OD persisted for more than 90 days in 35 patients (7.4%). After multiple binary logistic regression, OD was statistically associated with female gender (p =0.001; OR 95% CI: 2.46 [1.4-4.2]) and blue-collar occupational category (p =0.002; OR IC95%:3.1 [1.5-6.5]). A significant association was also noted between OD and professional seniority and absence from work duration (p =0.019; OR 95% CI: 0.97 [0.95-0.99] and p =0.03; OR 95% CI: 0.97 [0.95-0.99]) respectively.

OD is common in COVID-19 patients. The identification of its associated factors may contribute to enhancing the understanding of its mechanism and drive therapeutic options.

Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®.

Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3-18 months and who persisted with anosmia or hyposmia. The sample size was calculated with "satulator". The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40 IU of NPH insulin were placed on the nasal roof of each nostril for 15 min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment.

27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63-71) compared to the final mean of 83% (80-86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration.

The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

Transient or persistent hypo-anosmia is common in SARS‑CoV‑2 infection but olfactory pathway late-term morphometric changes are still under investigation. We evaluated late olfactory bulb (OB) imaging changes and their correlates with the olfactory function in otherwise neurologically asymptomatic COVID-19 patients. Eighty-three subjects (mean-age 43 ± 14 yr; 54 females; time-interval infection/MRI: 129±68 d) were affected by asymptomatic to mild COVID-19 in 2020 and 25 healthy controls (mean-age 40 ± 13 yr; 9 females) underwent 3T-MRI and olfactory function evaluation through anamnestic questionnaire and Sniffin' Sticks. Exclusion criteria were intensive care treatment or neurological involvement other than olfaction. Maximal OB area was measured blindly on high-resolution coronal T2w images by 2 observers. Patients were subdivided into (i) persistently hypo/anosmic, (ii) recovered normosmic, and (iii) never complaining smell dysfunction with proven normal olfactory function. No significant differences were observed among patients' subgroups (P = 0.76). Intraobserver and interobserver reliability were high (r = 0.96 and 0.86). Former COronaVIrus Disease 19 (COVID-19) patients had decreased mean maximal OB area than controls (6.52 ± 1.11 mm2 vs. 7.26 ± 1.17 mm2, P = 0.008) even when considering persistently hypo-anosmic (6.46 ± 0.90, P = 0.006) or normosmic patients at MRI (6.57 ± 1.25, P = 0.04). SARS-CoV-2 infection is associated with mid/late-term morphological changes in the OB, regardless of presence or persistence of olfactory dysfunction. The long-term consequences on olfactory aging need to be further investigated including possible links with neurodegenerative disorders.