Serological surveillance reveals a high exposure to SARS-CoV-2 and altered immune response among COVID-19 unvaccinated Cameroonian individuals (preprint)

Background Surveillance of COVID-19/SARS-CoV-2 dynamics is crucial to understanding natural history and providing insights into the populations exposure risk and specific susceptibilities. This study investigated the seroprevalence of SARS-CoV-2 antibodies, its predictors, and immunological status among unvaccinated patients in Cameroon. Materials and Methods A multicentre cross-sectional study was conducted between January and September 2022 in the town of Douala. Patients were consecutively recruited, and data of interest were collected using a questionnaire. Blood samples were collected to determine Immunoglobin titres (IgM and IgG) by ALFA, CD4+ cells by flow cytometry, and interferon gamma (IFN- {gamma}) and interleukin-6 (IL-6) by ELISA. Results A total of 342 patients aged 41.5 {+/-} 13.9 years were included. Most participants (75.8%) were asymptomatic. The overall prevalence of IgM and IgG was 49.1% and 88.9%, respectively. Ageusia and anosmia have displayed the highest positive predictive values (90.9% and 82.4%) and specificity (98.9% and 98.3%). The predictors of IgM seropositivity were being aged 60 - 70 years (aOR = 0.54, p = 0.02) and ageusia (aOR = 9.31, p = 0.01), whereas those of IgG seropositivity included health facility (aOR = 0.23, p = 0.02) and ageusia (aOR = 0.21, p = 0.04). CD4+, IFN-{gamma}, and IL-6 were impaired in seropositive individuals, with a confounding role of socio-demographic factors or comorbidities. Conclusion Although the WHO declared the end of COVID-19 as a public health emergency, the findings of this study indicate the need for continuous surveillance to adequately control the disease in Cameroon.

Dysosmia and dysgeusia as differential diagnostics for clinical triaging of COVID-19 cases (preprint)

Smell and taste disorders are recognized as frequent, and often the only, signs occurring in the early phase of SARS-Cov-2 infection and in many cases perdure as post-viral symptoms. This evidence raised a general reconsideration of chemosensory deficits, further suggesting that their appearance can be considered as a discriminative and predictive tool to detect COVID-19 cases. In this study, encompassing the first and second pandemic wave, participants estimated their olfactory and gustatory sensitivity, plus they were administered the validated Brief Smell Identification Test (BSIT). We observed that smell and taste impairments were mainly experienced by COVID-19-positive subjects with comparable severity of respiratory symptoms as non-COVID-19 patients. In addition, we noticed that the diagnostic power of subjective olfactory assessments upon SARS-Cov-2 infection is comparable to quantitative evaluation, suggesting that self-reporting could be adopted as the first line of intervention, anticipating more exhaustive procedures aimed at containing COVID-19 diffusion and consequently preserving general health. Overall, results from this work share similarity with other studies, therefore further underlying that olfactory and gustatory disbalance can be distinctive hallmarks in COVID-19 continuum.

Evaluating the Effect of Olfactory Training on Improving the Sense of Smell in Patients with COVID-19 with Olfactory Disorders: A Randomized Clinical Trial Study (preprint)

Background The COVID-19 disease is associated with many complications, including the disorder of the sense of smell, which is stable even months after the infection and negatively impacts the patient’s quality of life. Nursing interventions to solve this problem are among the nursing care priorities for these patients. Therefore, this study aimed to determine the effect of olfactory training on improving the sense of smell in patients suffering from olfactory disorders with COVID-19.Methods This randomized clinical trial was based on pre-test-post-test type on people who were referred with a positive polymerase chain reaction (PCR) test in Babol, Iran, under the supervision of Babol city health center with the disorder in the sense of smell. A total of 100 patients were selected by the available method and randomly assigned to two intervention and control groups. Both groups completed the Questionnaire of Olfactory Disorders - Negative Statements (QOD-NS) before the intervention. The olfactory training intervention group was exposed to four categories of main scents: phenylethyl alcohol (the smell of roses from rose geranium), eucalyptus (the smell of eucalyptus), citronol (the smell of lemon), and eugenol (the smell of cloves) twice a day, morning, and night for six weeks, rotating for 20 seconds each with a ten-second interval between each scent. After completing the olfactory training course, both groups answered the quality of life questionnaire about smell. Finally, the data were analyzed using SPSS version 21, independent paired t-tests.Results The average score of olfactory disorder in patients with COVID-19 before the intervention in the intervention and control groups was 24.32 ± 6.60 and 22.85 ± 8.04, respectively, which did not have a significant difference (P = 0.33). The values reached 19.60 ± 5.74 and 22.52 ± 7.39, statistically significant (P = 0.034).Conclusion Olfactory training effectively improved the sense of smell in patients with COVID-19 suffering from olfactory disorders. Therefore, this program should be taught by nurses to improve patients with COVID-19 with olfactory disorders after discharge.

[Interpretation of the 2021 American Academy of Allergy, Asthma and Immunology expert consensus on the treatment of postinfectious olfactory dysfunction].

Respiratory tract viruses are the second leading cause of olfactory dysfunction. Between 2019 to 2022, the world has been plagued by the problem of olfaction caused by the COVID-19. As we learn more about the impact of severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）, with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction（PIOD）. The Clinical Olfactory Working Group has proposed theconsensus on the roles of PIOD. This paper is the detailed interpretation of the consensus.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study.

OBJECTIVE: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection. METHODS: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. RESULTS: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). CONCLUSION: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations.

Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial.

INTRODUCTION: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss. METHODS: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale. RESULTS: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported. CONCLUSION: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

Unravelling anosmia, ageusia and clinical presentations in hospitalized Taiwanese patients with COVID-19: Insights and Implications (preprint)

Objectives The objective of this study was to investigate the clinical characteristics and outcomes of hospitalized COVID-19 patients presenting with anosmia and/or ageusia symptoms.Methods We conducted a retrospective observational study among 231 hospitalized patients with COVID-19 in Taiwan from April 2021 to July 2021. Detailed initial clinical symptoms, dyspnea grading, laboratory investigations, and admission outcomes were analyzed to elucidate the significance of anosmia and/or ageusia.Results Cough, fever, and dyspnea were the most common symptoms, while anosmia and/or ageusia accounted for only 8% of symptoms in hospitalized patients. Patients presenting with anosmia and/or ageusia had more severe initial clinical symptoms and comorbidities. A higher proportion of patients with anosmia and/or ageusia underwent initial endotracheal intubation and received emergency monoclonal antibody treatment for COVID-19 than those without these symptoms. However, there were no significant differences in the levels of inflammatory markers between the two groups.Conclusion Our study highlights the distinct clinical presentations of anosmia and/or ageusia in hospitalized COVID-19 patients. Anosmia and/or ageusia could be an important predictor of disease severity and may warrant early intervention in COVID-19 patients. Further studies are needed to confirm these findings

The Olfactory Dysfunction of COVID-19.

Until the coronavirus disease 2019 (COVID-19) pandemic, much of the scientific community and the general public lacked an appreciation of the impact of decreased smell function on everyday life, including the importance of this sensory system for safety, nutrition, and overall quality of life. It is now well established that the SARS-CoV-2 virus inflicts measurable but frequently reversible smell loss during its acute phase. Indeed, in many studies such loss is the most common symptom of COVID-19. Permanent or long-term deficits (i.e., deficits lasting over a year) may occur in up to 30% of those who have been infected, including the development of odor distortions (dysosmias; parosmias). This review presents up-to-date information on the epidemiology, severity, and pathophysiology of COVID-19-related smell dysfunction, including its association with psychological and neurological sequelae.

SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.

BACKGROUND: Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS). METHODS: Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice. RESULTS: Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1ß, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1ß, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein. CONCLUSIONS: Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

Diode laser in management of loss of taste sensation in patients with post-COVID syndrome: a randomized clinical trial.

OBJECTIVE: Loss of taste (ageusia) is a symptom observed following recovery from COVID-19 infection. The loss of taste and smell sensation may negatively affect patients' quality of life (QoL). The present study aimed to evaluate the effectiveness of the Diode Laser in managing loss of taste sensation in patients with post-COVID syndrome versus the placebo. MATERIAL AND METHOD: The study sample was 36 patients who complained of persistent loss of taste sensation following COVID-19. The patients were randomly assigned to one of the two groups according to the received treatment: Group I (laser treatment) and Group II (light treatment), with each patient receiving a diode laser treatment or placebo from the same operator. Taste sensation was subjectively measured after treatment for four weeks. RESULTS: The results demonstrated a significant difference between both groups regarding taste restoration after one month (p = 0.041), with Group II having a significantly higher percentage of cases 7 (38.9%) with partial taste restoration. In contrast, a significantly higher proportion of Group I 17 cases (94.4%) had complete taste restoration (p < 0.001). CONCLUSION: The present study concluded that using a Diode laser 810 nm aided in a more rapid recovery from loss of taste dysfunction.

Olfactory dysfunction in patients with Wilson's Disease.

INTRODUCTION: Many neurodegenerative disorders are associated with olfactory dysfunction (OD), but little is known about OD in Wilson's Disease (WD). We evaluated olfactory function in patients with WD. MATERIAL AND METHODS: OD was examined in 68 patients with WD and 70 sex- and age-matched healthy controls using subjective testing with 'Sniffin Sticks'. Threshold discrimination identification (TDI) score and its three components (odour detection threshold, discrimination, and identification) were assessed. RESULTS: Compared to controls, patients with WD had a significantly weaker sense of smell in terms of TDI (p < 0.01), odour discrimination (p < 0.01), and identification (p < 0.01), but not in terms of odour detection threshold (p = 0.27). Patients with predominantly neurological symptoms were characterised by greater OD by TDI (p < 0.01), odour detection threshold (p = 0.01), and discrimination (p = 0.03). The presence of pathological lesions (p = 0.04) in brain magnetic resonance imaging and generalised brain atrophy (p = 0.02) predisposed to worse TDI. In the WD group, weak inverse correlations between age and TDI score (r = -0.27), odour detection threshold (r = -0.3), and discrimination (r = -0.3) were found. Male gender was a risk factor for abnormal TDI in both WD and controls (both p = 0.02). CONCLUSIONS: Patients with WD, particularly older individuals, more frequently had OD than healthy volunteers. Predominantly neurological symptoms, and the presence of typical brain MRI changes, predisposed patients with WD to smell disorders.

Olfactory Function and Olfactory Disorders. / Riechen und Riechstörungen.

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.

Olfactory Dysfunction: Etiology, Diagnosis, and Treatment.

BACKGROUND: Disorders of the sense of smell have received greater attention because of the frequency with which they occur as a symptom of SARS-CoV-2 infection. Olfactory dysfunction can lead to profound reduction in quality of life and may arise from many different causes. METHODS: A selective literature review was conducted with consideration of the current version of the guideline issued by the Association of the Scientific Medical Societies in Germany. RESULTS: The cornerstones of diagnosis are the relevant medical history and psychophysical testing of olfactory function using standardized validated tests. Modern treatment strategies are oriented on the cause of the dysfunction. While treatment of the underlying inflammation takes precedence in patients with sinunasal dysosmia, olfactory training is the primary treatment option for other forms of the disorder. The prognosis is determined not only by the cause of the olfactory dysfunction and the patient's age, but also by the olfactory performance as measured at the time of diagnosis. CONCLUSION: Options for the treatment of olfactory dysfunction are available but limited, depending on the cause. It is therefore important to carry out a detailed diagnostic work-up and keep the patient informed of the expected course and prognosis.

Evaluation of subjective and tested olfactory dysfunction as a screening tool for COVID-19 in children.

INTRODUCTION: Olfactory dysfunction (OD) is an extremely frequent symptom of SARS-CoV-2 infection in adults. However, the symptomatology in the paediatric population remains understudied and heavily reliant on questionnaires. The aims of this study were to evaluate the prevalence of OD in children with SARS-CoV-2 infection and to assess the use of olfactory testing in predicting COVID-19 in children. Furthermore, we aimed to investigate the correlation between subjective and objective sense of smell in children. METHODS: Children aged 6-12 years presenting at Test Centre Aarhus for a reverse transcription PCR for SARS-CoV-2 were invited to participate during the study period (from 8 January to 22 February 2022). They underwent olfactory testing with Sniffin' Sticks 16 Identification Kit and they were asked about their subjective assessment of smell and any confounding factors. RESULTS: A total of 78 children completed inclusion of whom 51 had a positive SARS-CoV-2 PCR test. We found no correlation between either current SARS-CoV-2 status and Sniffin' Sticks Identification score (p = 0.500) or previous self-reported infection. We also found no correlation between subjective and objective sense of smell (p = 0. 109). CONCLUSION: The lack of correlation between SARS-CoV-2 infection and OD may indicate that OD is not a dominant symptom in children. Therefore, olfactory testing is not recommended as a screening method for SARS-CoV-2 as was suggested in adults. Likewise, subjective questioning is not a reliable tool in assessing olfactory function in children. FUNDING: Laura Danielsen received funding for salary from Forskningsfond Hospitalsenheden Vest (now Forskningsfond Regionshospitalet Gødstrup). Alexander Wieck Fjældstad wishes to acknowledge research salary funding for other projects from Velux Fonden. The sponsors had no say, roles or responsibilities in relation to the study, including (but not limited to) the study design, data collection, management, analysis or decision to publish. TRIAL REGISTRATION: Not relevant.