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.

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.

The Systemic Inflammation Index on admission is independently associated with length of stay in hospitalized COVID-19 patients

BACKGROUND: The early detection of factors predicting hospital length of stay (LOS) in patients affected by severe acute respiratory syndrome in Coronavirus 2 (SARS-CoV-2) disease (COVID-19) might facilitate therapeutic decisions and patient flow management. METHODS: We collected routine clinical and laboratory parameters and derived inflammatory indexes on admission in 65 consecutive COVID-19 patients transferred to the Unit of Respiratory and Infectious Disease of the University Hospital of Sassari (North-Sardinia, Italy) who were alive on discharge. RESULTS: Patients with prolonged length of stay (LOS) (PLOS >= 26 days, N.=22) had significantly higher chest CT severity scores, neutrophils, neutrophil lymphocyte ratio (NLR), aggregate index of systemic inflammation, Systemic Inflammation Response Index, Systemic Inflammation Index (SII), aspartate aminotransferase, lactate dehydrogenase (LDH), and rates of obesity and respiratory support, than non-PLOS patients (N.=43). In univariate analysis, LOS was significantly and negatively correlated with lymphocytes and monocytes, and positively correlated with Body Mass Index (BMI), intensity of care, chest CT severity score, NLR, platelet lymphocyte ratio, SII and LDH. In multivariate regression analysis, only the SII was significantly associated with LOS (beta=0.506, P=0.002) after adjusting for BMI, intensity of care, chest CT severity score and LDH. CONCLUSIONS: SII values on admission were independently associated with LOS in COVID-19 patients. Prospective studies in larger cohorts are required to confirm our findings and to determine the role of the SII in clinical decision making.

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.

Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study.

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

Clinical features of patients who had two COVID-19 episodes: a European multicentre case series.

OBJECTIVE: To investigate the clinical features of patients who had two demonstrated coronavirus disease 2019 (COVID-19) episodes. METHODS: Data of patients with both COVID-19 episodes were recruited from 22 March to 27 December 2020. The following outcomes were studied: epidemiological, comorbidities, prevalence and severity of general and otolaryngological symptom, olfactory, aroma, and gustatory dysfunctions. A comparison between first and second episodes was performed. RESULTS: Forty-five patients reported having two confirmed COVID-19 episodes. The majority of patients had mild infections in both episodes. The second clinical episode was significantly similar to the first. The symptom duration of the second episode was shorter than the first. The occurrence of loss of smell was unpredictable from the first to the second episode. CONCLUSION: The recurrence of COVID-19 symptoms is associated with a similar clinical picture than the first episode in patients with initial mild-to-moderate COVID episode. The pathophysiological mechanisms underlying the development of second episode remain uncertain and may involve either true reinfection or virus reactivation from sanctuaries.

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.

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia.

BACKGROUND: Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. CASE REPORT: This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. CONCLUSION: The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study.

BACKGROUND: The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined. METHOD: A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days. RESULTS: Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204-733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278-1043.5, p = 0.005). CONCLUSION: Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.

Remote psychophysical evaluation of olfactory and gustatory functions in early-stage coronavirus disease 2019 patients: the Bologna experience of 300 cases.

BACKGROUND: An objective evaluation of coronavirus disease 2019 in the first days of infection is almost impossible, as affected individuals are generally in home quarantine, and there is limited accessibility for the operator who should perform the test. To overcome this limitation, a recently validated psychophysical self-administered test was used, which can be performed remotely in the assessment of early-stage coronavirus disease 2019 patients. METHODS: Olfactory and gustatory functions were objectively assessed in 300 patients in the first 7 days from coronavirus disease 2019 symptom onset. RESULTS: Seventy per cent of the patients presented olfactory and/or gustatory disorders. The dysfunctions detected were mainly complete anosmia (47 per cent) or ageusia (38 per cent). A significant correlation was found between taste dysfunction and female gender (odds ratio = 1.936, p = 0.014) and fever (odds ratio = 2.132, p = 0.003). CONCLUSION: The psychophysical evaluation protocol proposed is an effective tool for the fast and objective evaluation of patients in the early stages of coronavirus disease 2019. Chemosensitive disorders have been confirmed to be frequent and early symptoms of the coronavirus infection, and, in a significant number of cases, they are the first or only manifestation of coronavirus disease 2019.