Recovery from COVID-19 related olfactory and gustatory dysfunction following omicron BA.1 subvariant infection: a six-month prospective study (preprint)

PurposeThe aim of the present study was to estimate the prevalence and the recovery rate of self-reported chemosensory dysfunction 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant.MethodsProspective study based on the sino-nasal outcome tool 22 (SNOT-22), item "sense of smell or taste" and additional outcomes. Results. Of 338 patients with mild-to-moderate COVID-19 completing the baseline survey, 294 (87.0%) responded to the 6-month follow-up interview. Among them, 101 (34.4 %) and 4 (1.4 %) reported an altered sense of smell or taste at baseline and at 6 months, respectively. Among the 101 patients with COVID-19-associated smell or taste dysfunction during the acute phase of the disease, 97 (96.0%) reported complete resolution at 6 months. The duration of smell or taste impairment was significantly shorter in vaccinated patients (p=0.007).ConclusionsCompared with that observed in subjects infected during the first wave of the pandemic, the recovery rate from chemosensory dysfunctions reported in the present series of patients infected during the predominance of the Omicron BA.1 subvariant was more favourable with a shorter duration being positively influenced by vaccination.

Safety of day-case endoscopic sinus surgery in England: An observational study using an administrative dataset (preprint)

Background: As elective surgical services recover from the COVID-19 pandemic a movement towards day-case surgery may reduce waiting lists. However, evidence is needed to show that day-case surgery is safe for many ENT operations including endoscopic sinus surgery (ESS). We aimed to investigate the safety of ESS in England. Methods: This was an observational, secondary analysis of administrative data. Participants were all patients in England undergoing elective ESS procedure aged ≥ 17 years during for the five years from 1st April 2014 to 31st March 2019. The exposure variable was day-case or overnight stay. The primary outcome was emergency readmission within 30 days post-discharge. Results: Data were available for 49,223 patients operated on across 129 NHS hospital trusts. In trusts operating on more than 50 patients in the study period, rates of day-case surgery varied from 100% to 20.6%. Rates of day-case surgery increased from 64.0% in 2014/15 to 78.7% in 2018/19. Day-case patients had lower rates of 30-day emergency readmission (odds ratio 0.71, 95% confidence interval 0.62 to 0.81). For secondary outcomes measures, there was no evidence of poorer outcomes for day-case patients. Outcomes for patients operated on in trusts with ≥80% day-case rates compared to patients operated on in trusts with <50% rates of day-case surgery were similar. Conclusions: ESS can safely be performed as day-case surgery at current rates. There is a potential to increase rates of day-case ESS in England, especially in departments that currently have low rates of day-case ESS.

COVID-19-related Smell and Taste Impairment with Widespread Diffusion of SARS-CoV-2 Omicron Variant (preprint)

Background. The aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate COVID-19 in the period from January 17, 2022 to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients tested positive for SARS-CoV-2 infection between March and April, 2020 (comparator period). Methods. Prospective study based on the sinonasal outcome tool 22 (SNOT-22), item sense of smell or taste and additional outcomes. Results. Patients characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%; 95% CI, 27.6-37.8) was significantly lower from that during the comparator period (66.9%; 95% CI, 62.3-71.3) (p

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge (preprint)

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.

Patient perspectives about participation in a chronic rhinosinusitis trial during the COVID pandemic: a qualitative study. (preprint)

• Telephone interviews were conducted with 19 MACRO trial participants from 5 ENT sites across the UK. • Trial participants experienced mixed levels of communication during the COVID period and some felt uninformed about the trial status and their clinical situation. • Participants were most concerned about getting COVID through interactions with other patients in hospital settings. Conversely, there was a high level of trust in healthcare professionals. • Pre-visit COVID-safety information, minimising contact with other patients, and strict waiting room management can facilitate the restart of the MACRO trial from the patient perspective. • Patient confidence in trial participation is likely to continue improving with COVID vaccination roll out.

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study. (preprint)

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19)Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7 – 18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs=0.182) and not significant (p=0.12).Conclusions: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions

Self-reported smell and taste recovery in COVID-19 patients: a one-year prospective study (preprint)

Purpose The aim of the present study was to estimate the one-year prevalence and recovery rate of self-reported chemosensory dysfunction in a series of subjects with previous mild-to-moderate symptomatic COVID-19. Methods Prospective study based on the SNOT-22 (item sense of smell or taste) and additional outcomes. Results 268/315 patients (85.1%) completing the survey at baseline also completed the follow-up interview. The 12-months prevalence of self-reported COVID-19 associated chemosensory dysfunction was 21.3% (95% CI: 16.5-26.7%). Of the 187 patients who complained of COVID-19 associated chemosensory dysfunction at baseline, 130 (69.5%; 95% CI 62.4-76.0%) reported complete resolution of smell or taste impairment, 41 (21.9%) reported a decrease in the severity, and 16 (8.6%) reported the symptom was unchanged or worse one year after onset. The risk of persistence was higher for patients reporting a baseline SNOT-22 score > o = 4 (OR=3.32; 95% CI: 1.32-8.36) as well as for those requiring > o = 22 days for a negative swab (OR=2.18; 95% CI: 1.12-4.27). Conclusion A substantial proportion of patients with previous mild-to-moderate symptomatic COVID-19 characterized by new onset of chemosensory dysfunction still complained on altered sense of smell or taste one-year after the onset.

High prevalence of long-term psychophysical olfactory dysfunction in patients with COVID-19 (preprint)

This study prospectively assessed the long-term prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 54 (37.2) being mildly microsmic, 16 (11.0%) moderately microsmic, 7 (4.8%) severely microsmic, and 10 patients (6.9%) being anosmic. At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearmans r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-CoV-2 infection.

An analysis of patients’ perspectives on qualitative olfactory dysfunction using social media (preprint)

SUMMARY Background The impact of qualitative olfactory disorders is underestimated. Parosmia is the triggered perception of distorted odours whereas phantosmia is the perception of odours in the absence of a trigger. Both can arise from post-infectious anosmia and have increased substantially since the outbreak of COVID-19. Methodology/Principal Thematic analysis of a social media support group for parosmia and phantosmia was used to articulate the perspectives and concerns of those affected by these debilitating olfactory disorders. Results A novel symptom (olfactory perseveration) was identified where a triggered, identifiable, and usually unpleasant olfactory percept persisted in the absence of an ongoing stimulus. Fluctuations in intensity and duration of perseveration, parosmia and phantosmia were observed. Coffee, meat, onion, and toothpaste were identified as common triggers of these disorders, but people struggled to describe the distortions, using words associated with disgust and revulsion. Common strategies to avoid triggers may result in a diet lacking in both nutrition and reward. The emotional aspect of living with qualitative olfactory dysfunction was evident and highlighted the detrimental impact on mental health. Conclusions The data acquired can inform rehabilitation strategies and drive our ongoing research into understanding the molecular triggers associated with parosmia, and research into patient benefit.

Altered Smell and Taste: anosmia, parosmia and the long impact of Covid-19 (preprint)

Abstract Background: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact on quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell. Methods: We conducted passive and active thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020. Results: Participants reported difficulty understanding, explaining and managing altered taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others. Conclusions: Our findings suggest altered taste and smell with Covid-19 lead to a severe disruption to daily living that impacts on psychological well-being and health. Moreover, this impact is broad, spanning flavour perception; desire and ability to eat and prepare food; weight gain, loss and nutritional sufficiency; emotional wellbeing; professional practice; intimacy; social bonding and erosion of peoples very sense of reality. Our findings should inform the training, assessment and treatment practices of health care professionals working with long Covid.

Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study (preprint)

Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. Methods: This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. Results: Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean{+/-}SD, C19+: -82.5{+/-}27.2 points; C19-: -59.8{+/-}37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset. Conclusions: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings [≤]2 indicate high odds of symptomatic COVID-19 (10

Clinical and Radiological Evaluations of COVID-19 Patients with Anosmia: Preliminary Report. (preprint)

Objective: To investigate clinical and radiological features of olfactory clefts of patients with mild coronavirus disease 2019 (COVID-19). Methods: Sixteen COVID-19 patients were recruited. The epidemiological and clinical data were extracted. Nasal complaints were assessed through the sino-nasal outcome test 22 (SNOT-22). Patients underwent psychophysical olfactory testing, olfactory cleft examination and CT-scan. Results: Sixteen anosmic patients were included. The mean Sniffin Sticks score was 4.6+/-1.7. The majority of patients had no endoscopical abnormality, with a mean olfactory cleft endoscopy score of 0.6+/-0.9. The olfactory clefts were opacified in 3 patients on the CT-scan. The mean radiological olfactory cleft score was 0.7+/-0.8. There were no significant correlations between clinical, radiological and psychophysical olfactory testing. Conclusion: The olfactory cleft of anosmic COVID-19 patients is free regarding endoscopic examination and imaging. The anosmia etiology would be not related to edema of the olfactory cleft.

New onset of loss of smell or taste in household contacts of home-isolated SARS-CoV-2 positive subjects (preprint)

Purpose To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients.Methods Cross sectional study based on ad hoc questions.Results Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p<0.001).Conclusion Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.

Objective olfactory testing in patients presenting with sudden onset olfactory dysfunction as the first manifestation of confirmed COVID-19 infection (preprint)

Abstract Background: The aims of this study are to investigate the COVID-19 status of patients with initial sudden olfactory anosmia (ISOA) using nasopharyngeal swabs for RT-PCR analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. Methodology: This prospective study included 78 ISOA patients who fulfilled a patient-reported outcome questionnaire and underwent a nasopharyngeal swabs. Among these, 46 patients performed psychophysical olfactory evaluation using sniffing tests. Based on the duration of the ISOA, two groups of patients were compared: patients with anosmia duration [≤]12 days (group 1) and those with duration >12 days (group 2). Results: Among group 1, 42 patients (87.5%) had a positive viral load regarding RT-PCR while 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. Among the 46 patients having performed a psychophysical olfactory evaluation, we observed anosmia in 52% (N=24), hyposmia in 24% (N=11) and normosmia in 24% (N=11) of patients. The viral load significantly decreased throughout the 14-days following the onset of the olfactory disorder. Conclusions: Our results support that a high proportion of ISOA patients are Covid+. Our study supports the need to add anosmia to the list of symptoms used in screening tools for possible COVID-19 infection.