PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.

Comparison of the incidence of smell and taste disorders between influenza and COVID-19.

OBJECTIVE: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX research network. METHODS: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. RESULTS: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. CONCLUSIONS: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effect of smell training on COVID-19 induced smell loss.

OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.

Taste loss in COVID-19 â€" psychophysical evidence supporting a low prevalence.

Much - possibly even too much - has been published about chemosensory dysfunction as a consequence of COVID-19. Studies have reported prevalence of taste loss in up to 89.9%, which is in a similar range as COVID-19 related smell loss. However, most of these publications rely solely on patients' self-reports. Only few studies used validated psychophysical tests to specifically address olfaction and gustation. Especially for gustation, it is evident that subjective reporting does not correlate well with more objective psychophysical findings, often leading to an overestimation of subjectively impaired taste.

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

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

Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study.

BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group. METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin'Sticks test (Delta, Omicron and control groups). RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls. CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.

Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting.

BACKGROUND: With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months. OBJECTIVE: To characterize symptoms 7 to 9 months after diagnosis of COVID-19. DESIGN: Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis. SETTING: From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis. PARTICIPANTS: Persons who were a part of the CoviCare program from 18 March to 15 May 2020. MEASUREMENTS: A standardized interview of symptoms consistent with COVID-19, with grading of intensity. RESULTS: Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%). LIMITATION: Limitations include generalizability and missing data for 34.8% of participants. CONCLUSION: Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients. PRIMARY FUNDING SOURCE: None.

Predictors of smell recovery in a nationwide prospective cohort of patients with COVID-19.

OBJECTIVE: To determine which factors (demographic, symptoms, comorbidities, and treatments) are associated with recovery of smell in patients with COVID-19 associated olfactory loss. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 associated smell and taste loss was launched April 10, 2020. After completing an initial entry survey, participants received detailed follow-up questionnaires 14 days, and 1, 3 and 6 months later. RESULTS: As of June 25, 2021, 798 participants met study inclusion criteria and completed 6-month questionnaires. Of demographic characteristics only age <40 years was positively associated with smell recovery (p < .003). Of symptoms, difficulty breathing was negatively associated with smell recovery (p < .004), and nasal congestion positively associated with smell recovery (p < .03). Of pre-existing comorbidities only previous head injury (p < .017) was negatively associated with smell recovery. None of the queried medications used to treat COVID were associated with better rates of smell recovery. CONCLUSIONS: Age <40 and presence of nasal congestion at time of COVID-19 infection were predictive of improved rates of smell recovery, while difficulty breathing at time of COVID-19 infection, and prior head trauma predicted worsened rates of recovery. Further study will be required to identify potential mechanisms for the other observed associations. Such information can be used by clinicians to counsel patients suffering COVID-19 associated smell loss as to prognosis for recovery.

Clinical, virological and immunological evolution of the olfactory and gustatory dysfunction in COVID-19.

PURPOSE: New-onset olfactory and gustatory dysfunction (OGD) represents a well-acknowledged COVID-19 red flag. Nevertheless, its clinical, virological and serological features are still a matter of debate. MATERIALS AND METHODS: For this cohort study, 170 consecutive subjects with new-onset OGD were consecutively recruited. Otolaryngological examination, OGD subjective grading, nasopharyngeal swabs (NS) for SARS-CoV-2 RNA detection and serum samples (SS) collection for SARS-CoV-2 IgG quantification were conducted at baseline and after one (T1), two (T2) and four weeks (T3). RESULTS: SARS-CoV-2 infection was confirmed in 79% of patients. Specifically, 43% of positive patients were detected only by SS analysis. The OGD was the only clinical complaint in 10% of cases. Concurrent sinonasal symptoms were reported by 45% of patients. Subjective improvement at T3 was reported by 97% of patients, with 40% recovering completely. Hormonal disorders and RNA detectability in NS were the only variables associated with OGD severity. Recovery rate was higher in case of seasonal influenza vaccination, lower in patients with systemic involvement and severe OGD. Not RNA levels nor IgG titers were correlated with recovery. CONCLUSION: Clinical, virological and serological features of COVID-19 related OGD were monitored longitudinally, offering valuable hints for future research on the relationship between host characteristics and chemosensory dysfunctions.

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients.

OBJECTIVE: This study aims to comprehensively evaluate olfactory and gustatory dysfunctions during the COVID-19 pandemic regarding onset, course, associated symptoms, prognosis and relation to patients' demographics, treatment received and other symptoms. PATIENTS& METHODS: This is a prospective study conducted on patients proven to be infected with COVID-19 and with olfactory/gustatory dysfunction symptoms. Detailed history was taken from each patient about the onset of this dysfunction, associated symptoms. Then follow-up survey was done after 6 months to evaluate the prognosis. RESULTS: 1031 patients were included in the study, aged 18 to 69 years old, with 31.8% were male. Olfactory/gustatory dysfunctions occurred after other COVID-19 symptoms in 43.5% of cases, occurred suddenly in 80.4% and gradually in 19.6%. These dysfunctions were anosmia & ageusia in 50.2%, hyposmia & hypogeusia in 23.3%, anosmia alone in 17.7%, phantosmia in 18%, Parosmia in 28.4%. In terms of recovery 6-month follow up, 680 patients (66%) recovered completely, 22.1% recovered partially while 11.9% did not recover. Most improvement occurred in the first two weeks. Headache, malaise, nasal obstruction and rhinorrhea were the commonest COVID-19 symptoms associated. CONCLUSION: Most recovery of olfactory/gustatory dysfunction in COVID-19 infection occurs at the first two weeks and is unrelated to patient demographics, treatment or olfactory training. Parosmia is an independent predictor for complete recovery, while phantosmia is significantly associated with lower probability of complete recovery.

Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients.

OBJECTIVE: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. METHODS: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. RESULTS: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P < 0.001). CONCLUSION: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6 months.

A structural equation model to examine the clinical features of mild-to-moderate COVID-19: A multicenter Italian study.

The purpose of this study was to evaluate the clinical features of mild-to-moderate coronavirus disease 2019 (COVID-19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory-confirmed COVID-19 infection were recruited. Patients completed a survey-based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild-to-moderate COVID-19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above-mentioned disorders was found (rs: 0.412; P < .001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory-confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P < .05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild-to-moderate Italian COVID-19 patients is significant both in suspected and laboratory-confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea.

Characteristics of taste dysfunction in COVID-19 subjects coming from two different countries.

Taste dysfunction (TD) has been recognised, together with olfactory dysfunction, as a key presenting symptom of COVID-19. The capability to recognise flavours, flavour intensities and aroma characteristics can be highly variable within the same population, as well as potentially diverse between culturally different populations. The aims of this study are to evaluate whether a difference in the types of TD presentation amongst COVID-19 positive subjects can be demonstrated and whether a difference exists between populations of different cultures.

Presence of gustatory and olfactory dysfunction in the time of the COVID-19 pandemic.

BACKGROUND: The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections. METHODS: Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed. RESULTS: Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men. CONCLUSIONS: Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Regional and Chronological Variation of Chemosensory Dysfunction in COVID-19: a Meta-Analysis.

BACKGROUND: Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction. METHODS: Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a Freeman-Tukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively. RESULTS: The overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment. CONCLUSION: The regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.

Is there a correlation between viral load and olfactory & taste dysfunction in COVID-19 patients?

OBJECTIVES: To evaluate the correlation between cycle threshold (Ct) value and occurrence of olfactory and taste dysfunction in COVID-19 patients. METHODS: This comparative study included COVID-19 patients diagnosed by reverse transcription- polymerase chain reaction (RT-PCR) based test at our hospital with mild to moderate disease. The demographic details and detailed clinical history of the patient, including history of loss of smell and taste was taken at the time of presentation. The patients were divided into 2 groups, group A: COVID-19 patients with OTD; group B: COVID-19 patients without OTD. 100 contiguous patients were recruited in each group. The COVID-19 test by RT-PCR was done and Ct value of the 3 genes: E (Envelope encoding) gene, N (Nucleocapsid encoding) gene, and RdRp (RNA-dependent RNA polymerase) gene, was used for data analysis. The Ct values of each of the three genes were compared between groups A and B. RESULTS: Group A and B did not differ significantly in terms of basic demographics. The differences in the Ct values of the 3 genes E gene, N gene and RdRp gene, of group A and B were found to be statistically significant (p = 0.005, p = 0.001 and p = 0.002, respectively). CONCLUSION: The patients with OTD had a lower Ct value at diagnosis, and hence, a higher viral load than those without OTD. The evaluation of Ct value and viral load in COVID-19 patients may help in further reducing the transmission of the virus in the community.

Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence.

BACKGROUND: Smell dysfunction has been recognized as an early symptom of SARS-CoV-2 infection, often occurring before the onset of core symptoms of the respiratory tract, fever or muscle pain. In most cases, olfactory dysfunction is accompanied by reduced sense of taste, is partial (microsmia) and seems to normalize after several weeks, however, especially in cases of virus-induced complete smell loss (anosmia), there are indications of persisting deficits even 2 months after recovery from the acute disease, pointing towards the possibility of chronic or even permanent smell reduction for a significant part of the patient population. To date, we have no knowledge on the specificity of anosmia towards specific odorants or chemicals and about the longer-term timeline of its persistence or reversal. METHODS: In this longitudinal study, 70 participants from a community in Lower Austria that had been tested positive for either IgG or IgM SARS-CoV-2 titers in June 2020 and a healthy control cohort (N = 348) underwent smell testing with a 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT). The test was performed in October 2020, i.e. 4 months after initial diagnosis via antibody testing. Results were analyzed using statistical tests for contingency for each smell individually in order to detect whether reacquisition of smell is dependent on specific odorant types. RESULTS: For all odorants tested, except the odor "smoke", even 4 months or more after acute SARS-CoV-2 infection, participants with a positive antibody titer had a reduced sense of smell when compared to the control group. On average, while the control cohort detected a set of 12 different smells with 88.0% accuracy, the antibody-positive group detected 80.0% of tested odorants. A reduction of accuracy of detection by 9.1% in the antibody-positive cohort was detected. Recovery of the ability to smell was particularly delayed for three odorants: strawberry (encoded by the aldehyde ethylmethylphenylglycidate), lemon (encoded by citronellal, a monoterpenoid aldehyde), and soap (alkali metal salts of the fatty acids plus odorous additives) exhibit a sensitivity of detection of an infection with SARS-CoV-2 of 31.0%, 41.0% and 40.0%, respectively. CONCLUSION: Four months or more after acute infection, smell performance of SARS-CoV-2 positive patients with mild or no symptoms is not fully recovered, whereby the ability to detect certain odors (strawberry, lemon and soap) is particularly affected, suggesting the possibility that these sensitivity to these smells may not only be lagging behind but may be more permanently affected.

Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

OBJECTIVE: The association between COVID-19 and chemosensory loss has garnered substantial attention, however to date little is known about the real-life consequences of impairment in this unique patient population. The aim of this study is to evaluate the quality of life (QOL) and personal safety deficits experienced by patients with COVID-19 infection. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 and/or a sudden change in smell and taste was launched April 10, 2020. Previously published questions on chemosensory-related QOL and safety events were asked at the 6-month follow-up survey. RESULTS: As of February 10, 2021, 480 eligible respondents took the 6-month questionnaire, of whom 322 were COVID-19 positive. Impact on QOL was substantial with 96% of subjects reporting at least one of the defined deficits, and over 75% reporting at least 3 of these. "Reduced enjoyment of food" was the most common complaint (87%), while 43% of subjects self-reported depression. The prevalence of safety-related issues was common in this population, with over 57% reporting at least one, and 36% reporting 2 or more events. Of the events asked, the inability to smell smoke that others could perceive was the most common at 45%. CONCLUSIONS: COVID-19 associated chemosensory losses have a real and substantial impact on both quality of life and safety, beyond mere inconvenience. The high prevalence of these issues despite a relatively short period of olfactory deficit should alert clinicians to the serious risks to an already vulnerable patient population.