Intranasal insulin for COVID-19-related smell loss.

BACKGROUND: 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®. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Associations between underlying diseases with COVID-19 and its symptoms among adults: a cross-sectional study.

Background: Specific underlying diseases were reported to be associated with severe COVID-19 outcomes, but little is known about their combined associations. The study was aimed to assess the relations of number of and specific underlying diseases to COVID-19, severe symptoms, loss of smell, and loss of taste. Methods: A total of 28,204 adult participants in the National Health Interview Survey 2021 were included. Underlying diseases (including cardiovascular diseases, cancer, endocrine diseases, respiratory diseases, neuropsychiatric diseases, liver and kidney diseases, fatigue syndrome, and sensory impairments), the history of COVID-19, and its symptoms were self-reported by structured questionnaires. Multivariable logistic regression models were used to assess the combined relation of total number of underlying diseases to COVID-19 and its symptoms, while mutually adjusted logistic models were used to examine their independent associations. Results: Among the 28,204 participants (mean ± standard deviation: 48.2 ± 18.5 years), each additional underlying disease was related to 33, 20, 37, and 39% higher odds of COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.29-1.37), severe symptoms (OR: 1.20, 95% CI: 1.12-1.29), loss of smell (OR: 1.37, 95% CI: 1.29-1.46), and loss of taste (OR: 1.39, 95% CI: 1.31-1.49). In addition, independent associations of sensory impairments with COVID-19 (OR: 3.73, 95% CI: 3.44-4.05), severe symptoms (OR: 1.37, 95% CI: 1.13-1.67), loss of smell (OR: 8.17, 95% CI: 6.86-9.76), and loss of taste (OR: 6.13, 95% CI: 5.19-7.25), cardiovascular diseases with COVID-19 (OR: 1.13, 95% CI: 1.03-1.24), neuropsychiatric diseases with severe symptoms (OR: 1.41, 95% CI: 1.15-1.74), and endocrine diseases with loss of taste (OR: 1.28, 95% CI: 1.05-1.56) were observed. Conclusion: A larger number of underlying diseases were related to higher odds of COVID-19, severe symptoms, loss of smell, and loss of taste in a dose-response manner. Specific underlying diseases might be individually associated with COVID-19 and its symptoms.

Mechanisms of SARS-CoV-2-associated anosmia.

Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.

Analysis of Interaction Between Odorant Receptors and Flexible Spike of SARS CoV-2- Key to Loss of Smell.

BACKGROUND: The development of a vaccine for SARS-CoV-2 is primarily focused on the structure of the spike (S) protein. The heavy glycosylation of S with flexible hinges at the stalk shields from antibody attachment. OBJECTIVE: This study deciphers the flexible nature of hinges responsible for binding the odorant receptor on neurons responsible for the loss of smell in COVID-19 patients. METHODS: The 3D structure via EPIK in Maestro, protein docking with ligands via Maestro protein analysis tool, and molecular dynamic simulation at 30 ns run using DESMOND was prepared. RESULTS: The data of the study strongly suggest that strong and stable bond formation results from the reaction between R:14: Trp and Phe at the residue, targeting the flexible hinges of SARS-CoV-2. The difference in the conformational structure of the S protein and its binding with the odorant receptor in COVID-19 is the prime factor for the loss of smell and taste in patients, as supported by the concept of Antigen (epitope) Antibody interaction by the stable formation of a hydrogen bond among odorant receptor and the S protein. The flexibility of structural proteins determines the binding potential of antibodies or other defense proteins produced to participate in the antigen-antibody reaction. CONCLUSION: Molecular and atomic details potentiate the design and screening of small molecules that can inhibit the fusion at entry level or odorant receptors and potentially be used in the prevention and treatment of infection, particularly when formulated as nasal drops, paving a new approach for pharmacologists in the treatment of COVID-19 infection.

Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2.

Since 2020, SARS-CoV-2 has caused a pandemic virus that has posed many challenges worldwide. Infection with this virus can result in a number of symptoms, one of which is anosmia. Olfactory dysfunction can be a temporary or long-term viral complication caused by a disorder of the olfactory neuroepithelium. Processes such as inflammation, apoptosis, and neuronal damage are involved in the development of SARS-CoV-2-induced anosmia. One of the receptors that play a key role in the entry of SARS-CoV-2 into the host cell is the transmembrane serine protease TMPRSS2, which facilitates this process by cleaving the viral S protein. The gene encoding TMPRSS2 is located on chromosome 21. It contains 15 exons and has many genetic variations, some of which increase the risk of disease. Delta strains have been shown to be more dependent on TMPRSS2 for cell entry than Omicron strains. Blockade of this receptor by serine protease inhibitors such as camostat and nafamostat can be helpful for treating SARS-CoV-2 symptoms, including anosmia. Proper understanding of the different functional aspects of this serine protease can help to overcome the therapeutic challenges of SARS-CoV-2 symptoms, including anosmia. In this review, we describe the cellular and molecular events involved in anosmia induced by SARS-CoV-2 with a focus on the function of the TMPRSS2 receptor.

Revealing the mystery of persistent smell loss in Long COVID patients.

COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.

Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Evaluation of olfactory dysfunction persistence after COVID-19: a prospective study.

OBJECTIVE: Alterations of the olfactory function in patients affected by COVID-19 often have an early onset and a variable duration ranging from a few weeks to months. The aim of this study was to evaluate olfactory dysfunction persistence after recovery from COVID-19, and potential related clinical-demographic conditions. PATIENTS AND METHODS: A total of 76 patients recovered from COVID-19 from at least 20 days with olfactory dysfunction during the infection were included in the study. For the subjective evaluation of olfactory function, a visual analogic scale (VAS) was used. The objective evaluation was performed with the use of the Sniffin' Sticks test. RESULTS: Objective assessment of olfactory function revealed that 48 (63.16%) patients were found to be normosmic (TDI ≥ 30.5), 26 (34.21%) were hyposmic (TDI from 30.5 to 16.5) and two (2.63%) were anosmic (TDI ≤ 16.5) at the time of the evaluation. These results did not show a significant difference between subjective and objective tests (p = 0.45). Most patients recovered their sense of smell within the first two months after recovery while a portion (22.2%) still experienced olfactory alterations 4-6 months after SARS-CoV-2 infection. Patients who had not recovered their sense of smell had a significantly longer period of SARS-CoV-2 positivity compared to patients that fully recovered (36.07 ± 7.78 days vs. 29 ± 7.89 days; p = 0.04). CONCLUSIONS: Our results suggest that the duration of the infection negatively correlates with the recovery of olfactory function.

Investigation on the Factors Associated with the Persistence of Anosmia and Ageusia in Saudi COVID-19 Patients.

The Coronavirus Disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in a worldwide pandemic of a highly infectious disease. The difficulty of dealing with COVID-19 is the broad spectrum of clinical manifestations that involves various pathophysiological mechanisms, severities, duration, and complications. This study aims to help emphasize the factors related to the persistence and duration of anosmia (loss of smell) and ageusia (loss of taste) as part of post-acute COVID-19 syndrome in Saudi COVID-19 patients via a retrospective cross-sectional design. Eight hundred and eighty-one participants were recruited between March and April 2021. Those participants were 18 years or older, recovered from the COVID-19 infection, and completed 14 days after the onset of the acute phase of the disease. Among the 881 recruited participants, 808 have submitted eligible responses and were included in data analyses. The most common persistent symptoms in post-acute COVID-19 syndrome were anosmia (33.8%) and ageusia (26.4%). The data also showed a significant association between female sex and the incidence and the persistence of anosmia and ageusia. In multivariable analysis, anosmia during the acute phase was associated with BMI, asthma and shortness of breath, while anosmia during the post-acute phase was associated with sex. Ageusia during the acute phase was associated with sex, myalgia and arthralgia, while ageusia in the post-acute phase was associated with sex.

Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting billions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.

Delayed recovery from severe acute respiratory syndrome coronavirus-2 related anosmia predicts incomplete olfactory restoration.

OBJECTIVE: This study aimed to assess the olfactory recovery rates and patterns in a cohort of coronavirus disease 2019 positive patients, and to investigate the clinical predictors of poor long-term olfactory restoration. METHODS: An observational retrospective study was conducted on 146 patients between September 2020 and January 2021 at a tertiary referral hospital. Coronavirus disease 2019 positive patients with olfactory dysfunction were sent a modified version of the COVID-19 Anosmia Reporting Tool for Clinicians via e-mail. RESULTS: The difference in median recovery time between complete recovery and incomplete or no recovery was statistically significant. On multivariate analysis, the only significant factor associated with incomplete or no recovery was anosmia duration. CONCLUSION: After a mean time of 5.6 months from severe acute respiratory syndrome coronavirus-2 infection, persistent olfactory disorders were self-reported in 36.7 per cent of patients. Complete recovery was more likely to occur within 15 days. Given the high prevalence of coronavirus disease 2019, a large number of patients are expected to suffer from long-term olfactory morbidity.

New Onset of Smell and Taste Loss Are Common Findings Also in Patients With Symptomatic COVID-19 After Complete Vaccination.

The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID-19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient-reported outcome questionnaire from patients who developed symptomatic SARS-CoV-2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID-19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:419-421, 2022.

Frequency of olfactory dysfunction in pregnant women with SARS-CoV-2 infection.

INTRODUCTION: In patients with COVID-19, olfactory dysfunction and anosmia have been reported, which in pregnant women occur in up to 24.2 %. OBJECTIVE: To know the frequency at which pregnant women with SARS-CoV-2 infection have olfactory dysfunction. METHODS: Age, gestational age, temperature, presence of nasal constipation or rhinorrhea, myalgia, headache, cough or chest pain were asked. Whether patients perceived and identified the scent of grape juice, coffee powder and menthol was evaluated. Central tendency and dispersion measures, frequencies and percentages were used. Sensitivity, specificity, positive and negative predictive value were calculated. Mann-Whitney's U-test and contrast of proportions were used for comparisons between groups. RESULTS: There was a higher proportion of women with cough, headache, dyspnea, myalgia, odynophagia, rhinorrhea, chest pain, and anosmia in SARS-CoV-2-positive women. In patients without COVID-19, 88.9 % detected each one of the scents; only 31.8 % of the positive group detected grapes scent, 47.7 % coffee and 59.1 % menthol, which had the highest percentages of sensitivity (40 %), specificity (21 %), positive predictive value (59 %) and negative predictive value (11 %). CONCLUSION: Olfactory dysfunction occurs in a significant percentage of pregnant women with COVID-19.

INTRODUCCIÓN: En pacientes con COVID-19 se ha reportado disfunción olfatoria y anosmia; en la mujer embarazada se presenta hasta en 24.2 %. OBJETIVO: Conocer la frecuencia con la que las mujeres embarazadas e infección por SARS-CoV-2 tienen disfunción olfatoria. MÉTODOS: Se preguntó edad, edad gestacional, temperatura, presencia de constipación nasal o rinorrea, mialgias, cefalea, tos o dolor torácico, además de evaluar si las mujeres percibían e identificaban el aroma de jugo de uva, café en polvo y mentol. Se utilizaron medidas de tendencia central y dispersión, frecuencias y porcentajes. Se calculó sensibilidad, especificidad, valor predictivo positivo y negativo. La U de Mann-Whitney y el contraste de proporciones sirvieron para las comparaciones entre los grupos. RESULTADOS: Hubo mayor proporción de mujeres con tos, cefalea, disnea, mialgias, odinofagia, rinorrea, dolor torácico y anosmia en mujeres positivas a SARS-CoV-2. De las pacientes sin COVID-19, 88.9 % detectó cada uno de los aromas; solo 31.8 % del grupo positivo detectó el aroma a uva, 47.7 % el de café y 59.1 % el de mentol, el cual tuvo los porcentajes más altos en sensibilidad (40 %), especificidad (21 %), valores predictivos positivo (59 %) y negativo (11 %). CONCLUSIÓN: la disfunción olfatoria se presenta en un porcentaje importante de las mujeres embarazadas con COVID-19.

COVID-19 and its effects on neurological functions.

Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.

[Clinical manifestations of COVID-19 in children]. / Nevrologicheskie proyavleniya COVID-19 u detei.

The neurological symptoms of COVID-19 in children (in Dyurtyuli area, Republic of Bashkortostan) are analyzed and brief review of the literature is undertaken in the paper. 137 children underwent swab test for COVID-19. The disease was diagnosed in 9 of them. Only respiratory symptoms were observed in 3 children, a combination of respiratory with anosmia or/and headache - in 3, asymptomatic form - in another 3. A case of a 7-years old girl suffering from COVID-19 with respiratory symptoms as well as anosmia and headache is presented. According to the review of the literature, COVID - 19 in children is usually milder than in adults, but in some cases may lead to neurological consequences. Multisystem inflammatory syndrome may lead to the development symptoms of encephalopathy (altered mental status, headache) and stroke. Autoimmune complications such as Gillian-Barre syndrome develop simultaneously or after resolving of the infectious process. The development of viral meningoencephalitis in COVID-19 is questionable.

Implementing a COVID-19 specialist smell clinic: experience at the Wrightington, Wigan and Leigh Teaching Hospitals (WWL), NHS Foundation Trust, United Kingdom.

INTRODUCTION: It is clear that a proportion of patients continue to suffer long-lasting symptoms following acute infection with coronavirus disease 2019 (COVID-19). Persistent olfactory dysfunction is one of the commonest complaints reported in the condition colloquially known as long COVID (now known as post-acute sequelae of SARS-CoV-2 infection (PASC)). The prevalence, risk factors and clinical course of long COVID olfactory dysfunction are not yet well understood. At present, the main stay of treatment is olfactory training. Quantitative olfactory testing and impacts on patient quality of life have not been widely studied. This study describes our experiences at Wrightington, Wigan and Leigh Teaching Hospitals, UK (WWL) of establishing a COVID-19 smell clinic, along with preliminary data on patient demographics, baseline smell test scores and quality of life questionnaire scores before olfactory training. METHODS: We piloted a COVID-19 smell clinic. We recorded patient demographics and clinical characteristics then performed clinical assessment of each patient. Quantitative measurements of olfactory dysfunction were recorded using the University of Pennsylvania Smell Identification Test (UPSIT). We measured the impact of olfactory dysfunction on patient quality of life using the validated English Olfactory Disorders Questionnaire (eODQ). RESULTS: 20 patients participated in the clinic. 4 patients were excluded from analysis due to missing data. Median age was 35 years. 81% (n=13) of the participants were female. 50% (n=8) of patients suffered with a combination of anosmia/ageusia and parosmia, whilst 43% (n=7) of patients suffered with anosmia/ageusia without parosmia. Almost all the patients registered UPSIT scores in keeping with impaired olfaction. Patient scores ranged from 22 to 35, with the median score at 30. All patients reported that their olfactory dysfunction had an impact on their quality of life. The median eODQ score reported was 90, with scores ranging from 42 to 169 out of a maximum of 180. CONCLUSION: We have demonstrated that it is simple and feasible to set up a COVID-19 smell clinic. The materials are inexpensive, but supervised completion of the UPSIT and eODQ is time-consuming. Patients demonstrate reduced olfaction on quantitative testing and experience significant impacts on their quality of life as a result. More research is needed to demonstrate if olfactory training results in measurable improvements in smell test scores and quality of life.

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

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

Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.

BACKGROUND: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. METHODS AND FINDINGS: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. CONCLUSIONS: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.