To determine whether intensive olfactory training provides better chances of recovery than classic protocols in persistent dysosmia after Covid-19.

In the literature, olfactory training holds pride of place in the management of post-infection olfactory disorder, with a classic 4-odor protocol. On the other hand, few studies have assessed the benefit of more intensive training.

This prospective randomized clinical trial (No. 2020-A01397-32) assessed olfactory training for persistent dysosmia due to COVID-19, with 5 weeks' to 12 months' progression. Patients were divided between 2 groups, receiving a classical 4-odor protocol (n=49) or an intensive 8-odor protocol (n=30). Olfaction was assessed in consultation on the Sniffin' Sticks test, the DyNaChron self-reported olfaction questionnaire and a visual analogue scale (VAS), at inclusion (V1) and at 4 and 8 months (V2 and V3, respectively).

Both protocols significantly improved subjective olfactory assessment on VAS, with non-significant trends for improvement on psychophysical tests. There was no significant difference in olfactory recovery between the classic and intensive protocols. Adhesion to the training program decreased markedly beyond 4 months.

Intensive olfactory training did not increase the chances of olfactory recovery compared to the classic protocol in a population with persistent dysosmia following COVID-19 infection.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

 Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4).

 To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients.

 We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample.

 The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes.

 Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.

Chemosensory impairment is an outstanding symptom of SARS-CoV-2 infections. We hypothesized that measured sensory impairments are accompanied by transcriptomic changes in the foliate papillae area of the tongue. Hospital personnel with known SARS-CoV-2 immunoglobulin G (IgG) status completed questionnaires on sensory perception (n = 158). A subcohort of n = 141 participated in forced choice taste tests, and n = 43 participants consented to donate tongue swabs of the foliate papillae area for whole transcriptome analysis. The study included four groups of participants differing in IgG levels (≥ 10 AU/mL = IgG+; < 10 AU/mL = IgG-) and self-reported sensory impairment (SSI±). IgG+ subjects not detecting metallic taste had higher IgG+ levels than IgG+ participants detecting iron gluconate (p = 0.03). Smell perception was the most impaired biological process in the transcriptome data from IgG+/SSI+ participants subjected to gene ontology enrichment. IgG+/SSI+ subjects demonstrated lower expression levels of 166 olfactory receptors (OR) and 9 taste associated receptors (TAS) of which OR1A2, OR2J2, OR1A1, OR5K1 and OR1G1, as well as TAS2R7 are linked to metallic perception. The question raised by this study is whether odorant receptors on the tongue (i) might play a role in metal sensation, and (ii) are potential targets for virus-initiated sensory impairments, which needs to be investigated in future functional studies.

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.

Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2.

We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction.

We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time.

Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation.

Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.

Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function.

To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function.

This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing.

History of COVID-19.

The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests.

Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all).

In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

To develop a French Short Version of the Questionnaire of Olfactory Disorders-Negative Statements (Fr-sQOD) to assess the quality of life impairments of patients with olfactory dysfunction (OD).

Patients with OD and controls were enrolled from 2 academic centers. Individuals completed the Fr-sQOD, an OD visual analog scale severity, and the French version of the sinonasal outcome tool-22 (SNOT-22). Cronbach α was used to measure the internal consistency of Fr-sQOD. The reliability and the external validity of Fr-sQOD were assessed through a test-retest approach and by correlating Fr-sQOD with SNOT-22 scores, respectively. The external validity was assessed by correlation analysis between Fr-sQOD and the result of an assessment of the severity of OD on a visual analog scale.

Eighty patients completed the evaluations. The internal consistency was adequate (Cronbach α .96), and the test-retest reliability was high in the entire cohort (rs = 0.877, P < .001). The correlation between Fr-sQOD total scores and the severity of OD was moderate but significant (rs = -0.431; P = .001) supporting an acceptable external validity. Patients with OD had a significantly higher score of Fr-sQOD than healthy individuals (P < .001), indicating a high internal validity.

The Fr-sQOD is a reliable and valid self-administered tool in the evaluation of the impact of OD on quality of life of French-speaking patients.

Recently acquired olfactory dysfunction (OD) has emerged as one of hallmark manifestations of the novel Corona virus disease (COVID-19), but the evolution of its spontaneous recovery has remained inconclusive, with reports of persistence of OD beyond six months of onset. We undertook this systematic review and meta-analysis with a view to generating a pooled recovery rate of COVID-19 associated olfactory dysfunctions and attempt to examine the predictors of olfactory recovery. Systematic review and meta-analysis. A systematic search of Scopus, Google Scholar, and PubMed data bases, comprising all longitudinal studies reporting the trajectory of COVID-19 related OD was carried out. The pooled recovery rate was estimated with random-effects model, and the potential heterogeneity of the subgroup sources was analyzed using meta-regression test. After the PRISMA selection process 28 studies from 16 countries were included, with a total of 5,175 OD patients, among 11,948 COVID-19 cases. The estimated global pooled recovery rate of OD was 82.7% (95% CI, 77.46%-88.04%), with a pooled median duration of OD of 11.6 days. Only 2 out of 28 studies had recovery data beyond a period of 2 months. But no significant difference was found in the recovery rate regarding the length of follow up (P = 0.840). Studies that conducted objective olfactory assessments showed significant higher recovery rate than those with subjective assessments (P = 0.001). Although ten studies (36%) reported > 90% recovery, nine studies (32%) documented persistence of OD in > 25% of their patients. Five out of 6 studies showed that hyposmia tended to show complete recovery than anosmia. Age, co-morbidities, and intra-nasal treatments had no effects. Test of homogeneity between subgroups using the Cochran's Q test was not significant (Q = 0.69, P = 0.40). Our meta-analysis revealed high rate of early and medium term recovery of COVID-19 related OD. However, it also showed disturbing rates of persistence of OD. Anosmia tended to be predictive of residual OD than hyposmia. Age, co-morbidities, intra-nasal corticosteroid and decongestants, had no effects on OD recovery.

This article does not intend to comprehensively review the existing literature on coronavirus disease 2019 (COVID-19)-associated smell disorders, but aims to summarize scientific evidence for otorhinolaryngological practice and provide recommendations for diagnosis and treatment of persistent smell disorders following COVID-19.

Transient loss of smell is a common symptom of influenza and other upper respiratory infections. Loss of taste is possible but rare with these illnesses, and patient reports of 'taste loss' typically arise from a taste / flavor confusion. Thus, initial reports from COVID-19 patients of loss of taste and chemesthesis (i.e., chemical somatosensation like warming or cooling) were met with skepticism until multiple studies confirmed SARS-CoV-2 infections could disrupt these senses. Many studies have been based on self-report or on single time point assessments after acute illness was ended. Here, we describe intensive longitudinal data over 28 days from adults aged 18-45 years recruited in early 2021 (i.e., prior to the Delta and Omicron SARS-CoV-2 waves). These individuals were either COVID-19 positive or close contacts (per U.S. CDC criteria at the time of the study) in the first half of 2021. Upon enrollment, all participants were given nose clips, blinded samples of commercial jellybeans (Sour Cherry and Cinnamon), and scratch-n-sniff odor identification test cards (ScentCheckPro), which they used for daily assessments. In COVID-19 cases who enrolled on or before Day 10 of infection, Gaussian Process Regression showed two distinct measures of function - odor identification and odor intensity - declined relative to controls (exposed individuals who never developed COVID-19). Because enrollment began upon exposure, some participants became ill only after enrollment, which allowed us to capture baseline ratings, onset of loss, and recovery. Data from these four cases and four age- and sex- matched controls were plotted over 28 days to create panel plots. Variables included mean orthonasal intensity of four odors (ScentCheckPro), perceived nasal blockage, oral burn (Cinnamon jellybeans), and sourness and sweetness (Sour Cherry jellybeans). Controls exhibited stable ratings over time. By contrast, COVID-19 cases showed sharp deviations over time. Changes in odor intensity or odor identification were not explained by nasal blockage. No single pattern of taste loss or recovery was apparent, implying different taste qualities might recover at different rates. Oral burn was transiently reduced for some before recovering quickly, suggesting acute loss may be missed in datasets collected only after illness ends. Collectively, intensive daily testing shows orthonasal smell, oral chemesthesis and taste were each altered by acute SARS-CoV-2 infection. This disruption was dyssynchronous for different modalities, with variable loss and recovery rates across both modalities and individuals.

Objective: This study aimed to investigate the clinical characteristics and outcomes of ear-nose-throat (ENT) symptoms in SARS-CoV-2 Omicron infected patients resulting from local transmission. Methods: A convenience sampling network survey was conducted among individuals infected with SARS-CoV-2 to examine the characteristics and progression of ENT symptoms associated with local transmission. The survey comprised 52 questions, and univariable and multivariable logistic regression analyses were employed to assess the rate, severity, and outcome of ENT symptoms across different genders and age groups. Results: Among the 1,366 individuals included in the investigation, a peak in new infections occurred on 20th December, and the majority (78.4%) were female. The most common symptoms reported were coughing (90.6%), nasal congestion (77.2%), and runny nose (74.3%). Otologic symptoms were predominantly represented by tinnitus (29.7%). Conclusion: The rate of specific symptoms showed a significant correlation with age and gender. It is crucial to provide timely medical intervention, especially for female patients. This study offers a comprehensive understanding of the symptom spectrum in individuals infected with the virus, providing valuable insights for the development of targeted symptom management strategies.

To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures.

Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits.

During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection.

When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants.

3.

Olfactory dysfunction associated with coronavirus 2 (SARS-CoV-2) infection is in most cases transient, recovering spontaneously within a few days. However, in some patients it persists for a long time, affects their everyday life and endangers their health. Hence, we focused on patients with persistent loss of smell. The aim of this study was to evaluate olfactory dysfunction using a standardized test. Due to the pandemic, olfactory testing was performed online. Smell tests (Odorized Markers Test, OMT) were sent home to the patients. Together with the smell self-testing, participants reported and assessed several parameters (age, sex, subjective assessment of smell and taste, nasal patency, etc.) in an online questionnaire. Based on the questionnaire outcomes, the results were sent to the patients along with a list of participating otolaryngologists who provided them with professional care. From March to June 2021, 1025 patients requested smell testing, of these, 824 met the inclusion criteria of this study. The duration of the olfactory dysfunction at the time of testing ranged from 1 month to 1 year. Using the OMT, impaired smell ability-anosmia or hyposmia-was confirmed in 82.6% of participants. A total of 17.4% of participants were determined to be normosmic however, more than 50% of them complained of parosmia and/or phantosmia. Our study demonstrates the relevance of psychophysical smell testing and its suitability for remote use during the pandemic. This study also revealed several correlations between prolonged olfactory dysfunction and the monitored parameters.

Smell disorders are the most frequent persistent coronavirus disease 2019 (COVID-19) complications.

To describe the patterns and characteristics of persistent smell and taste disorders in Egyptian patients.

Assessment was done to 185 patients (adults = 150, age: 31.41 ± 8.63 years; children = 35; age: 15.66 ± 1.63 years). Otolaryngology and neuropsychiatric evaluations were done. Measurements included: A clinical questionnaire (for smell and taste); sniffin' odor, taste and flavor identification tests and the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS).

Duration of disorders was 11.53 ± 3.97 ms (6-24 ms). Parosmia (n = 119; 64.32%) was developed months after anosmia (3.05 ± 1.87 ms). Objective testing showed anosmia in all, ageusia and flavor loss in 20% (n = 37) and loss of nasal and oral trigeminal sensations in 18% (n = 33) and 20% (n = 37), respectively. Patients had low scoring of sQOD-NS (11.41 ± 3.66). There were no specific differences in other demographics and clinical variables which could distinguish post-COVID-19 smell and taste disorders in children from adults.

The course of small and taste disorders are supportive of the nasal and oral neuronal compromises. Post-COVID-19 taste and trigeminal disorders were less frequent compared to smell disorders. Post-COVID-19 flavor disorders were solely dependent on taste and not smell disorders. There were no demographics, clinical variables at onset or specific profile of these disorders in children compared to adults.

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

Anosmia is common with respiratory virus infections, but loss of taste or chemesthesis is rare. Reports of true taste loss with COVID-19 were viewed skeptically until confirmed by multiple studies. Nasal menthol thresholds are elevated in some with prior COVID-19 infections, but data on oral chemesthesis are lacking. Many patients recover quickly, but precise timing and synchrony of recovery are unclear. Here, we collected broad sensory measures over 28 days, recruiting adults (18-45 years) who were COVID-19 positive or recently exposed (close contacts per U.S. CDC criteria at the time of the study) in the first half of 2021. Participants received nose clips, red commercial jellybeans (Sour Cherry and Cinnamon), and scratch-n-sniff cards (ScentCheckPro). Among COVID-19 cases who entered the study on or before Day 10 of infection, Gaussian Process Regression showed odor identification and odor intensity (two distinct measures of function) each declined relative to controls (close contacts who never developed COVID-19), but effects were larger for intensity than identification. To assess changes during early onset, we identified four COVID-19 cases who enrolled on or prior to Day 1 of their illness â€" this allowed for visualization of baseline ratings, loss, and recovery of function over time. Four controls were matched for age, gender, and race. Variables included sourness and sweetness (Sour Cherry jellybeans), oral burn (Cinnamon jellybeans), mean orthonasal intensity of four odors (ScentCheckPro), and perceived nasal blockage. Data were plotted over 28 days, creating panel plots for the eight cases and controls. Controls exhibited stable ratings over time. By contrast, COVID-19 cases showed sharp deviations over time. No single pattern of taste loss or recovery was apparent, implying different taste qualities might recover at different rates. Oral burn was transiently reduced for some before recovering quickly, suggesting acute loss may be missed in data collected after acute illness ends. Changes in odor intensity or odor identification were not explained by nasal blockage. Collectively, intensive daily testing shows orthonasal smell, oral chemesthesis and taste were each altered by acute COVID-19 infection, and this disruption was dyssynchronous for different modalities, with variable loss and recovery rates across modalities and individuals.

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin' Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

The COVID-19 pandemic has led to significant morbidity and mortality, with the former impacting and limiting individuals requiring high physical fitness, including sportspeople and emergency services.

Observational cohort study of 4 groups: hospitalised, community illness with on-going symptoms (community-symptomatic), community illness now recovered (community-recovered) and comparison. A total of 113 participants (aged 39 ± 9, 86% male) were recruited: hospitalised (n = 35), community-symptomatic (n = 34), community-recovered (n = 18) and comparison (n = 26), approximately five months following acute illness. Participant outcome measures included cardiopulmonary imaging, submaximal and maximal exercise testing, pulmonary function, cognitive assessment, blood tests and questionnaires on mental health and function.

Hospitalised and community-symptomatic groups were older (43 ± 9 and 37 ± 10, P = 0.003), with a higher body mass index (31 ± 4 and 29 ± 4, P < 0.001), and had worse mental health (anxiety, depression and post-traumatic stress), fatigue and quality of life scores. Hospitalised and community-symptomatic participants performed less well on sub-maximal and maximal exercise testing. Hospitalised individuals had impaired ventilatory efficiency (higher VE/V̇CO₂ slope, 29.6 ± 5.1, P < 0.001), achieved less work at anaerobic threshold (70 ± 15, P < 0.001) and peak (231 ± 35, P < 0.001), and had a reduced forced vital capacity (4.7 ± 0.9, P = 0.004). Clinically significant abnormal cardiopulmonary imaging findings were present in 6% of hospitalised participants. Community-recovered individuals had no significant differences in outcomes to the comparison group.

Symptomatically recovered individuals who suffered mild-moderate acute COVID-19 do not differ from an age-, sex- and job-role-matched comparison population five months post-illness. Individuals who were hospitalised or continue to suffer symptoms may require a specific comprehensive assessment prior to return to full physical activity.

Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals.

Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia.

Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD.

Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.

Olfactory dysfunction is a typical post-COVID-19 presentation, affecting patients' quality of life. There are currently multiple treatment options in this group of patients such as oral and intranasal corticosteroids, olfactory training, oral vitamin-mineral supplementation, amongst others. This meta-analysis aims to consolidate existing evidence for current therapies in patients with persistent olfactory dysfunction related to COVID-19 infection and evaluate the possible role of corticosteroid add-on therapy in olfactory training.

A systematic review and meta-analysis to study current treatments/interventions for olfactory dysfunction in post-COVID-19 infection were conducted. Data were pooled for the meta-analysis. The outcomes include subjective or objective olfactory assessment major and minor adverse reactions.

Eleven studies (1414 participants) were included in this review, with six studies (916 participants) then assessed for the meta-analysis. Combined treatment of intranasal corticosteroid (INCS) with olfactory training (OT) has no benefit over OT monotherapy from both a VAS score improvement and identification component of Sniffin' Sticks test standpoint. In addition, there were no differences in improvement of TDI score between combined oral corticosteroid (OCS) with OT therapy compared to OT alone. Olfactory function was, however, significantly improved after OT.

There were no significant differences in the improvement of olfactory scores in combination INCS+OT or OCS+OT therapies compared to OT monotherapy. However, there is improvement in olfactory function after OT.

The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the aetiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against post-COVID-19 condition. Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition.

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with ten household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 3,356 self-reported a positive and 602 a negative COVID-19 diagnosis (COVID+ and COVID-, respectively); 1,267 were awaiting test results (COVID?). The rest reported no respiratory illness and were grouped by symptoms: sudden smell/taste changes (STC, N=4,445), other symptoms excluding smell or taste loss (OthS, N=832), and no symptoms (NoS, N=416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% Confidence Interval (CI): 15-28%), 47% in smell (95%-CI: 37-56%), and 17% in oral irritation (95%-CI: 10-25%) intensity. In all groups, perceived intensity of smell (r=0.84), taste (r=0.68), and oral irritation (r=0.37) was correlated. Our findings suggest most reports of taste dysfunction with COVID-19 were genuine and not due to misinterpreting smell loss as taste loss (i.e., a classical taste-flavor confusion). Assessing smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and helps to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.

Taste disorders (TDs) have been reported to be very common in patients suffering from coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus. In most of the hitherto conducted studies, a gustatory assessment was performed on the basis of surveys or self-reports by patients. The aim of our study was to undertake an objective assessment of four basic taste qualities by conducting tasting sessions that allowed detection thresholds in COVID-19 Tunisian patients and to study their associations with inflammation.

This analytical cross-sectional study was conducted on 89 patients aged between 21 to 70 years who had been diagnosed with COVID-19. We used Burghart taste strips to assess taste perception of the four taste qualities, i.e., sour, bitter, sweet, and salty. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured.

Taste disorders were reported by 40.4% of the patients, while objective assessments revealed that 63.8% of participants were suffering from hypogeusia and/or ageusia. Sour taste was the most altered (70.8%) gustatory quality. Patients with severe COVID-19 had significantly lower sour and bitter taste scores when compared to patients with minor/moderate forms. There was no significant association between serum inflammatory markers and taste disorders. However, the relationship between bitter and sweet taste qualities and IL-1β levels was significant (p = 0.018 and p = 0.041).

Our results demonstrate the interest in the objective assessment of taste dysfunctions in COVID-19 patients.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

The objective of this study was to determine prevalance, severity, course, and long-term findings of smell and taste disorders of coronavirus disease 2019 (COVID-19) patients in mild-moderate and severe-critical disease spectrum.

All adult patients conducted in our hospital with positive severe acute respiratory syndrome coronavirus 2 between March and April 2020 were surveyed during disease course and those with olfactory and taste loss were re-surveyed to determine the course and progress of these symptoms after at least 12-month follow-up. Demographic features and clinical findings were evaluated as well as disease severity.

A total of 77 patients with smell and/or taste loss symptoms were included in the study. At diagnosis, 58 (75.3%) patients had loss of smell and 75 (97.4%) had loss of taste. After a follow-up period of 12-14 months, 12 (15.6%) patients had ongoing loss of smell and six (8%) patients had ongoing loss of taste. Three (3.9%) patients complained of cacosmia and 5 (6.5%) complained of parosmia at follow-up. The presence of ongoing visual analog scale scores of smell and/or taste was not statistically significant between male and female patients. When presence and severity of symptoms were compared by disease severity, no statistically significant difference was found.

Smell and taste loss seem to be among the presenting symptoms of COVID-19. The prognosis and the treatment of the smell loss and taste loss in COVID-19 patients remains unclear. To improve and accelerate recovery, the pathophysiology and the treatment options must be validated.

Persistent olfactory dysfunction (OD) is the second most common symptom of post coronavirus disease-19 (COVID-19) now being termed long-COVID. Its prevalence after recovery from COVID-19 is estimated to be 12% after nearly 6 months of follow-up. It thus becomes imperative for the treating clinicians to update themselves with the pathophysiology of this post COVID disability as well as the tools for diagnosis and the available treatment options. A systematic literature search was performed as per PRISMA guidelines in MEDLINE, Cochrane Library, LILACS, Google Scholar, ClinicalTrials.gov, and medRxiv databases. The keywords used were covid-19, Olfactory Disorders, Smell, Anosmia, PVOD, Post Viral Olfactory Disorders, post-covid and post haul. All articles were studied for definition, mechanism, diagnostic tests and treatment options for post COVID OD. 33 published articles and 8 ongoing trials were found relevant and included after full-text review. SARS-CoV-2 can cause conductive, neural and central OD. Olfactory evaluation can be done both subjectively (visual analogue scale) and objectively (Sniffin' sticks, Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test and modified Davidson's alcohol sniff test). They can be used to detect and follow-up patients. Despite several on-going clinical trials, the most reliable and advisable treatment option available till date is olfactory training.

COVID-19 caused by SARS-CoV-2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS-CoV-2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID. We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs. Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID-19.

The COVID-19 pandemic is the result of the SARS-CoV-2 virus, which has caused more than 100 million infections and more than 2.5 million deaths worldwide, representing a serious public health problem. The gold method for detecting this virus is qRT-PCR, which is a semiquantitative technique where the viral load can be established through its cycle threshold (Ct). It has also been reported that COVID-19 generates long-term symptoms (post-COVID-19).

After three months, a survey was performed on 70 COVID-19 confirmed patients; subsequently, we divided them into four groups (persistent symptoms, chemo-sensitive, cognitive issues, and changes in habit) in order to determine the correlation between viral load and post-COVID-19 symptoms.

Data show that fatigue, nervousness, anosmia, and diet changes are common long-term symptoms; in addition, a negative correlation was found between viral load and the number of post-COVID-19 symptoms.

COVID-19 generates long-term symptoms which can cause problems with psychological and social repercussions.

It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

The objective of this research was to analyze the effects of the SARS-CoV-2 virus on the sensory and cognitive perception of mild and severe COVID-19 diagnosed and recovered consumers versus healthy consumers. Three groups of 50 consumers each (healthy vs. mild and severe COVID-19 diagnosed with 30 days after recovery) were used for the evaluation of instant coffee stimuli in concentrations: 4.40, 2.93, 2.20, 1.76, and 1.47% weight (w)/volume (v) and determine their discriminating power, emotions, and memories. Sensory tests were performed remotely. Results indicated that healthy consumers perceived higher intensities in most of the sensory attributes (with the exception of Burnt-A, Bitter-T, Acid-T, and Astringent-T attributes) compared to consumers who presented mild and severe COVID-19. Therefore, consumers diagnosed with mild and severe COVID-19 had a higher discrimination power in the attributes smell, basic tastes, and flavor. Healthy consumers could only discriminate two attributes that correspond to basic flavors. Consumers with mild and severe COVID-19 diagnosis elicited the highest number of negatives emotions (such as bored, disgusted, worried, guilty, wild, and aggressive) and negative memories (disease, pain, death, hurt, obesity, conflict personal, addiction, stench poverty, and accident) than healthy consumers. It is concluded that there were no significant differences between the consumer panels for the identification of sensory attributes. However, P-Healthy consumers perceived the highest intensities in most sensory attributes compared to those in the PCOVID19-Mild and PCOVID19-Severe panels. Finally, consumers diagnosed with mild or severe COVID-19 used a higher number of emotions and memories than those of the healthy panel.

Investigating the effects of COVID-19 on sensory and cognitive perception can be useful for industry and researchers in the sensory field who wish to understand the effects of the disease in order to generate new protocols for the selection and training of people, as well as the possible development and innovation of new products focused on perception of consumers recovered from COVID-19.

To study the incidence of the smell and taste disturbance in the COVID-19 patients and a follow up at 4 months to observe for the duration of resolution of these symptoms. This is a multicentric prospective study carried out in 3 different countries, from April, 2020 to January, 2021. The COVID-19 positive patients, aged between 15 and 60 years, were inquired about the presence of any smell or taste related symptoms. The same patients were followed up with the telephonic interview after 2 months and then after 4 months, respectively. The duration of resolution of the smell and taste disturbance symptoms was noted. Total of 188 COVID-19 positive patients, average age 33.1 ± 1.7 years, 54.2% males and 45.8% female were included in the study. The smell disturbance was present in 60.6% (hyposmia 36.1%, anosmia 20.2%, and parosmia 4.2%) and taste disturbance in 28.7% of patients (hypogeusia 20.2%, ageusia 6.9%, and parageusia 1.6%). There was improvement of anosmia by 97.4, hyposmia by 95.6%, parosmia by 100%, ageusia by 100%, hypogeusia 94.8%, and parageusia by 66.7%, at 4 months follow up. The present study concludes that the smell and taste disturbances are one of the main early presenting features of the COVID-19 infection. The temporary effect of the COVID-19 infection on the olfactory and gustatory pathway was also highlighted with more than 95% patients improving at 4 months of follow up.

Chemosensitive dysfunctions are now considered as frequent and early symptoms of coronavirus disease 2019 (COVID-19). In the last few weeks, researchers' greatest efforts have been focusing mainly on the analysis of olfactory disorders, neglecting taste dysfunctions. According to our psychophysical evaluations, it can be inferred that the pathogenesis of taste disorders in COVID-19 patients is largely smell-independent. Moreover, isolated gustatory disorders are highly specific of SARS-CoV-2 infection. For these reasons, it is essential that gustatory dysfunctions, like olfactory disorders, are included in the COVID-19 guidelines.

Olfactory dysfunction (OD)-including anosmia and hyposmia-is a common symptom of COVID-19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD; however, little is known about its benefits and optimizations after SARS-CoV-2 infection.

This study aimed to assess whether olfactory training performance can be optimized using more fragrances over a shorter period of time in patients with persistent OD after COVID-19. In addition, we determined the presence of other variables related to OD and treatment response in this population.

This multicenter randomized clinical trial recruited 80 patients with persistent OD and prior COVID-19 infection for less than 3 months. The patients were divided into 2 groups receiving either 4 or 8 essences over 4 weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after the treatment.

Significant olfactory improvement was measured subjectively and using the UPSIT in both groups; however, no significant differences between the groups were observed. Additionally, the presence of olfactory fluctuations was associated with higher UPSIT scores.

These data suggest that training intensification by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, fluctuant olfaction seems to be related to a higher score on the UPSIT.