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.

Determinants of excess mortality during the COVID-19 pandemic in 18 countries of the CMOR consortium : Christiana Demetriou

Many countries suffered excess all-cause mortality during the COVID-19 pandemic. This study aims to identify factors associated with excess mortality rates (EMR) in partaking countries during 2020. Weekly all-cause death counts for 2015-2020 were extracted from national databases for Australia, Austria, Brazil, Cyprus, Denmark, Estonia, France, Georgia, Israel, Italy, Mauritius, Norway, Peru, Slovenia, Sweden, USA, Ukraine and UK. EMR per 100,000 population were gauged using a 5-year mean baseline. Separate OLS multiple linear regressions explored pre-pandemic country profiles including healthcare system, geographic, socio-economic and population factors. Feature selection methods detected the main factors contributing to 2020 EMR. The health system model showed that an extra nurse per 1,000 and a 1% increase in Healthcare Access and Quality Index reduces EMR by 41.7% (p = 0.019) and 0.48% (p = 0.034). The model was statistically significant (R

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction

Background Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added. Objectives 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection. 2) To keep the evidence up-to-date, using a living systematic review approach. Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Register;Central Register of Controlled Trials (CENTRAL);Ovid MEDLINE;Ovid Embase;Web of Science;ClinicalTrials.gov;ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. Selection criteria We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. Main results We included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin. Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intra nasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are Linable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very Low. We are unable to draw meaningful conclusions from the numerical results. Authors' conclusions There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Differential Functional Responses of Neutrophil Subsets in Severe COVID-19 Patients.

Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters in COVID-19, including the emergence of low density neutrophils (LDN) that are associated with severe disease. The functional capabilities of these neutrophil clusters and correlation with gene and protein expression are unknown. To define host defense and immunosuppressive functions of normal density neutrophils (NDN) and LDN from COVID-19 patients, we recruited 64 patients with severe COVID-19 and 26 healthy donors (HD). Phagocytosis, respiratory burst activity, degranulation, neutrophil extracellular trap (NET) formation, and T-cell suppression in those neutrophil subsets were measured. NDN from severe/critical COVID-19 patients showed evidence of priming with enhanced phagocytosis, respiratory burst activity, and degranulation of secretory vesicles and gelatinase and specific granules, while NET formation was similar to HD NDN. COVID LDN response was impaired except for enhanced NET formation. A subset of COVID LDN with intermediate CD16 expression (CD16Int LDN) promoted T cell proliferation to a level similar to HD NDN, while COVID NDN and the CD16Hi LDN failed to stimulate T-cell activation. All 3 COVID-19 neutrophil populations suppressed stimulation of IFN-γ production, compared to HD NDN. We conclude that NDN and LDN from COVID-19 patients possess complementary functional capabilities that may act cooperatively to determine disease severity. We predict that global neutrophil responses that induce COVID-19 ARDS will vary depending on the proportion of neutrophil subsets.

OLDER PERSON’S ASSESSMENT SERVICE (OPAS): DELIVERING COMPREHENSIVE GERIATRIC ASSESSMENT (CGA) IN THE EMERGENCY DEPARTMENT (ED)

Introduction Innovative models of service delivery are required to provide Comprehensive Geriatric Assessment for older patients presenting to the Emergency Department with frailty syndromes. Method In 2018, the Older Person’s Assessment Service began a liaison service to the ED, taking referrals from the medical and ED teams for patients who presented with frailty syndromes (falls, cognitive impairment, care dependence, polypharmacy). The service saw 437 patients April–August 2018. 76% of the patients assessed were discharged by utilising available community services, rapid access outpatient follow up and inpatient reablement off the acute site. The service was estimated to avoid 50–80 admissions per month to medicine (saving 17–23 beds a year) and was commissioned as a permanent service. Phase 2 In 2020, a dedicated unit within ED was allocated to OPAS, enabling the acceptance of patients directly from triage and from the Ambulance Service by direct referral. This provided rapid access to specialist assessment, continued access to Elderly Care services, avoided exposure to coronavirus related admissions and the risks of nosocomial infection associated with admission. The service operates from 8 am-4 pm on weekdays. Results Between June 2020 and October 2021, the service saw 1,173 new patients. 988 patients (84.5%) were discharged off the acute site on the day of assessment. 68 (5.79%) patients were admitted to other facilities run by the Health Board (e.g Inpatient Reablement). The average age of an OPAS patient was 83 yrs and had a CFS > 5. Readmission rate at 14 days was 4% (47).Of the 253 patients who were admitted to an inpatient setting, 13.5% (35) contracted nosocomial covid-19. Conclusion The service has been supported and funded to expand into extended weekday hours as a result of this success and there are plans for future 7 day working.

Rhinology in review: from COVID-19 to biologicals.

We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

The UK national registry of ENT surgeons with coronavirus disease 2019: one year on.

OBJECTIVES: To report the one-year findings of the UK national registry of ENT surgeons with suspected or confirmed coronavirus disease 2019, and the results of a survey on the coronavirus disease 2019 experience of UK ENT trainees. METHOD: An online registry was created in April 2020. A separate survey was circulated electronically to all members of the Association of Otolaryngologists in Training. RESULTS: The registry recorded 98 clinicians with confirmed or suspected coronavirus disease 2019. The majority of infections were reported in the first wave of spring 2020. Two ENT surgeons were hospitalised and one died. The majority suspected workplace exposure, with a significant proportion attributing this to a lack of personal protective equipment at a time before formal guidance had been introduced. Of the ENT trainees surveyed, almost one-third believed that they had contracted coronavirus disease 2019. CONCLUSION: This highlights the importance of ongoing risk-reduction measures, including optimal personal protective equipment and vaccination.

High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: a matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation.

BACKGROUND: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. METHODOLOGY: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. RESULTS: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. CONCLUSION: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation?

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.

The outcome of olfactory impairment in patients with otherwise paucisymptomatic coronavirus disease 2019 during the pandemic.

OBJECTIVE: This study aimed to measure the duration and recovery rate of olfactory loss in patients complaining of recent smell loss as their prominent symptom during the coronavirus disease 2019 outbreak. METHOD: This was a prospective telephone follow-up observational study of 243 participants who completed an online survey that started on 12 March 2020. RESULTS: After a mean of 5.5 months from the loss of smell onset, 98.3 per cent of participants reported improvement with a 71.2 per cent complete recovery rate after a median of 21 days. The chance of complete recovery significantly decreased after 131 days from the onset of loss of smell (100 per cent sensitive and 97.7 per cent specific). Younger age and isolated smell loss were associated with a rapid recovery, whereas accompanying rhinological and gastrointestinal symptoms were associated with longer loss of smell duration. CONCLUSION: Smell loss, occurring as a prominent symptom during the coronavirus disease 2019 pandemic, showed a favourable outcome. However, after 5.5 months from the onset, around 10 per cent of participants still complained of moderate or severe hyposmia.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects (benefits and harms) of interventions to treat olfactory dysfunction in people with COVID-19 infection. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Six month follow-up of self-reported loss of smell during the COVID-19 pandemic.

INTRODUCTION: Loss of smell and taste is now recognised as amongst the most common symptoms of COVID-19 and the best predictor of COVID-19 positivity. Long term outcomes are unknown. This study aims to investigate recovery of loss of smell and the prevalence of parosmia. METHODOLOGY: 6-month follow-up of respondents to an online surgery who self-reported loss of smell at the onset of the CO- VID-19 pandemic in the UK. Information of additional symptoms, recovery of loss of smell and the development of parosmia was collected. RESULTS: 44% of respondents reported at least one other ongoing symptom at 6 months, of which fatigue (n=106) was the most prevalent. There was a significant improvement in self-rating of severity of olfactory loss where 177 patients stated they had a normal smell of smell while 12 patients reported complete loss of smell. The prevalence of parosmia is 43.1% with median interval of 2.5 months (range 0-6) from the onset of loss of smell. CONCLUSIONS: While many patients recover quickly, some experience long-term deficits with no self-reported improvement at 6 months. Furthermore, there is a high prevalence of parosmia even in those who report at least some recovery of olfactory func- tion. Longer term evaluation of recovery is required.

Efficacy of corticosteroid therapy in the treatment of long- lasting olfactory disorders in COVID-19 patients.

BACKGROUND: The growing number of COVID-19 patients with long-lasting olfactory disorders makes it necessary to identify ef- fective treatments that enhance the spontaneous recovery of olfactory function. METHODS: Multicentre randomised case-control study that involved 18 patients with COVID-19 related anosmia or severe hyposmia for more than 30 days. Nine patients were prescribed systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days. The other 9, untreated, patients were used as controls. The olfactory function was evaluated with CCCRC test at 20 and 40 days from the first evaluation. RESULTS: In the control group, a median olfactory score of 20 (IQR 30) was detected at baseline. At the 20-day control there was no significant improvement in olfactory function. The improvement in olfactory performance became significant at the 40-day follow-up compared to baseline scores [60 (IQR 60) versus 20 (IQR 30)]. In the treatment group, patients had a mean olfactory score of 10 (IQR 15) at initial control. At the 20-day control, a significant im-provement in the olfactory scores, compared to the baseline, was detected [70 (IQR 40) versus 10 (IQR 15)]. Olfactory function further improved at 40 days [median score 90 (IQR 50)]. Patients in the treatment group reported significantly higher improvements of the olfactory scores than the controls at both the 20-day [40 (IQR 45) versus 10 (IQR 15)] and 40-day [60 (IQR 40) versus 30 (IQR 25)] evaluations. CONCLUSIONS: Based on the results of this study, the mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity.