Diagnostic accuracy of the screenings Sniffin' Sticks Test (SST-12) in COVID-19 induced olfactory disorders.

Objective olfactory function can be assessed using validated olfactory tests like the Sniffin' Sticks Test (SST). However, their extensive nature makes them less suitable for clinical practice. To address this, shorter olfactory tests like the screenings Sniffin' Sticks Test (SST-12) can be used for screening purposes and reduce testing time. The SST-12 serves as a diagnostic tool for screening olfaction in cases unrelated to COVID-19. However, these screening tests are uncertain regarding their accuracy in detecting olfactory dysfunction in patients with COVID-19 as the plausible cause. We aim to determine the diagnostic accuracy of the SST-12 in adults with post-COVID-19 olfactory dysfunction. We performed a diagnostic accuracy study with data from 113 consecutive COVID-19 diagnosed patients who experienced objectified smell loss ever since. At approximately 6 months after their diagnosis, all participants underwent the SST (reference standard), part of the SST was the SST-12 (index test). Diagnostic accuracy of the SST-12 is measured as negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity. The SST-12 detected smell loss in 85 patients among 91 patients with smell loss and ruled out smell loss in 15 patients among the 22 patients without smell loss based on the reference standard. Making sensitivity 93.4% (CI 0.87-0.97), and specificity 68.2% (CI 0.48-0.85). Out of the 92 patients with a positive test result on SST-12, 85 patients had indeed smell loss (PPV 92.4% CI 0.86-0.97), and out of the 21 patients with a negative test result, 15 patients had no smell loss regarding the reference standard (NPV 71.4% CI 0.50-0.88). The findings suggest that the SST-12 holds promise as a useful tool for identifying individuals with smell loss, also in individuals with COVID-19 as cause, but it is important to have a good understanding of the interpretation of the results of the SST-12 when considering its implementation in clinical practice.

Squamous Cell Carcinoma Antigen in the Follow-up of Patients With Head and Neck Cancer.

OBJECTIVE: to determine if the tumor marker squamous cell carcinoma antigen (SCC-Ag) observed over time may contribute to the early detection of recurrence, metastasis, and second primary tumors in the follow-up of patients with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: A retrospective analysis of patients with HNSCC and at least one SCC-Ag measurement was conducted. Hazard ratios (HRs) were used to determine the correlation between SCC-Ag and an event. SETTING: patients with HNSCC, treated in the Antoni van Leeuwenhoek Hospital in The Netherlands between 2010 and 2020 were used for the analysis. METHODS: Data from 789 patients were used on event-free survival (EFS) with time-dependent Cox models. In addition to current (most recent) SCC-Ag (also dichotomized into high and low as done for clinical practice), average SCC-Ag and change between SCC-Ag measurements (delta SCC-Ag) were considered, using restricted cubic splines to explore nonlinear relationships. RESULTS: Dichotomized SCC-Ag values (HR = 3.01, 95% confidence interval [CI]: 2.17-4.18) and the delta SCC-Ag (HR = 1.15, 95% CI: 1.07-1.22) predicted EFS better than models using the cumulative average or current value of SCC-Ag, also after adjusting for tumor site, stage, age, and gender. A strong association was observed when using delta SCC-Ag as a linear predictor in the subgroup of oropharynx patients (HR = 4.88, 95% CI: 2.71-8.79). CONCLUSION: Dichotomized and delta SCC-Ag values can be important markers for EFS, during the follow-up of patients treated for HNSCC. These results were more evident in patients with oropharyngeal cancer.

One-year psychophysical evaluation of COVID-19-induced olfactory disorders: a prospective cohort study.

BACKGROUND: Olfactory disorders are common in COVID-19. While many patients recover within weeks, a notable number of patients suffer from prolonged olfactory disorders. Much research has focused on the acute phase of olfactory disorders in COVID-19; however, there is still inconsistency regarding the prognosis. We aim to assess both objective and subjective olfactory function in patients with persisting olfactory disorders following COVID-19, 1 year after diagnosis. METHODS: We objectively measured olfactory function in 77 patients who initially had COVID-19-induced smell disorders, 1 year after confirmed diagnosis. These patients previously underwent two objective measurements at approximately 3 and 6 months after COVID-19, in the context of the COCOS trial (COrticosteroids for COvid-19-induced loss of Smell). The main outcome measurement was TDI score (threshold-discrimination-identification) on Sniffin' Sticks Test (SST). Secondary outcomes included objective gustatory function on Taste Strip Test (TST), self-reported olfactory, gustatory and trigeminal function on a visual analogue scale (VAS) and outcomes on questionnaires about quality of life, and nasal symptoms. RESULTS: The findings of this study show that 1 year following COVID-19, the median TDI score increased to 30.75 (IQR 27.38-33.5), regarded as normosmia. The median TDI score started at 21.25 (IQR 18.25-24.75) at baseline and increased to 27.5 (IQR 23.63-30.0) at 6 months following COVID-19. The increase of 9.5 points on the TDI score between baseline and 1 year after COVID-19 marks a clinically relevant improvement. Regarding the self-reported VAS score (1-10) on sense of smell, it increased from 1.2 (IQR 0.4-3.0) at baseline to 3.2 (IQR 1.4-6.0) at 6 months and further improved up to 6.1 (IQR 2.7-7.5) after 1 year. Objective gustatory function increased with 2 points on TST a year after diagnosis. Self-reported olfactory, gustatory, and trigeminal functions also improved over time, as did quality of life. CONCLUSIONS: Objective and self-reported olfactory function continued to improve 1 year after COVID-19. The median TDI score of 30.75 (IQR 27.38-33.5) is regarded as normosmia, which is a favorable outcome. However, the rate of improvement on TDI score reduces over time.

A Comparative Analysis of the Incidence, Severity and Duration of Smell and Taste Loss in COVID-19 Cases Versus Non-COVID-19 Cases: A Longitudinal Cohort Study.

The COVID-19 pandemic has highlighted the relevance of olfactory and gustatory disorders. However, these symptoms can also be caused by various other factors. In this study we aimed to compare the incidence, severity and duration between COVID-19 related and non-COVID-19 related smell and taste disorders. We conducted a longitudinal cohort study using data from the Dutch biobank Lifelines, which includes over 167,000 participants. The data were collected using 27 questionnaires distributed between March 2020 and May 2022. Descriptive data and the incidence of smell and taste loss in both groups were calculated. To visualize the proportion of severity rates of symptoms, a heatmap was created. A survival analysis was conducted and presented in a reversed Kaplan-Meier curve to show the probability of having persistent smell loss in both groups. The study included 235,722 participants. The incidence of smell loss was higher in the COVID-19 positive group, when compared to the COVID-19 negative group. We found varying degrees of symptom severity in COVID-19 positive cases, ranging from mild to severe, while non-COVID-19 related cases mostly reported mild symptoms. The survival outcome for smell and taste loss was 0.12 (SE 0.03, 95% CI 0.07-0.21) in COVID-19 related cases, and was 0.17 (SE 0.03, 95% CI 0.12-0.24) in cases related to other causes. This study reveals a higher incidence and severity of smell and taste loss in individuals with COVID-19 compared to non-COVID-19 related cases. However, non-COVID-19 related smell and taste loss tend to have a longer duration.

Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. METHODS: We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin' Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed. RESULTS: Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment (n = 58) or placebo group (n = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. CONCLUSIONS: This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. TRIAL REGISTRATION: This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

COCOS trial: COrticosteroids for COVID-19-induced loss of Smell-protocol for a single-centred, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Hyposmia and anosmia are common in COVID-19. Most patients regain normal smell within 4 weeks, but severe loss of smell persists roughly in 20% after 2 months and may last up to a year or longer. These persistent smell disorders greatly influence daily life. It is hypothesised that COVID-19 induces inflammation around the olfactory nerve and in the olfactory pathway, leading to smell disorders. Corticosteroids might reduce this local inflammatory response and improve smell. METHODS AND ANALYSIS: We will conduct a single-centre, randomised, placebo-controlled trial to determine the efficacy of a short high-dose treatment of oral prednisolone for persistent loss of smell after COVID-19 in the early phase. We will include 116 patients with persistent (>4 weeks) loss of smell within 12 weeks of COVID-19 diagnosis, based on a positive PCR/antigen test. One group receives 40 mg of prednisolone for 10 days and the other group receives matching placebo treatment. In addition, all patients will perform smell training for 12 weeks. The primary outcome is objective olfactory function measured by means of sniffin' sticks test. Secondary outcomes are objective gustatory function by means of taste strips test and subjective taste and smell ability, trigeminal sensations, quality of life and nasal symptoms, measured by three questionnaires. These outcomes will be measured at inclusion before treatment and 12 weeks later. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Medical Center Utrecht approved the research protocol (21-635/G-D, October 2021). The trial results will be shared in peer-reviewed medical journals and scientific conferences. TRIAL REGISTRATION NUMBER: NL9635. EUCTR2021-004021-71-NL.