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Article ; Online: Olfactory function and viral recovery in COVID-19.

Mazzoli, Marco / Molinari, Maria Angela / Tondelli, Manuela / Giovannini, Giada / Ricceri, Riccardo / Ciolli, Ludovico / Picchetto, Livio / Meletti, Stefano

Brain and behavior

2021 Volume 11, Issue 3, Page(s) e02006

Abstract: ... olfactory function with viral recovery.: Methods: Between 15 and 30 April 2020, hospitalized patients ... 19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery ... Background: Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients ...

Abstract	Background: Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients. The purpose of our study was to objectively assess smell impairment in COVID-19 patients and to correlate olfactory function with viral recovery. Methods: Between 15 and 30 April 2020, hospitalized patients with confirmed SARS-CoV-2 infection underwent an objective assessment of olfactory function with the Smell Identification subtest of the Sniffin' Sticks Test (SI-SST). Association between viral recovery and SI-SST performance was evaluated. Results: 51 patients were enrolled (49% males, mean age 66.2 ± 14.6 years). At the time of test administration, 45% were clinically recovered and 39% were virus-free. Objective hyposmia/anosmia was found in 45% of the patients. Subjective olfactory disorders showed no association with the clinical or viral recovery status of the patients. On the contrary, none of the patients with anosmia and the 5% of hyposmic patients at test had viral recovery. The relative risk for hyposmic patients to be still positive at swab test was 10.323 (95% CI 1.483-71.869, p < .0001). Logistic regression analysis showed an independent and significant correlation between viral clearance and SI-SST scores (OR = 2.242; 95% CI 1.322-3.802, p < .003). ROC curve analysis confirmed that a SI-SST > 10.5 predicts viral clearance with 79% sensitivity and 87% specificity (AUC = 0.883). Conclusion: Hyposmia is part of COVID-19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery. SI-SST is an easy and safe instrument, and further large multicentric studies should assess its value to predict infection and recovery.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Anosmia/diagnosis ; Anosmia/epidemiology ; Anosmia/physiopathology ; Anosmia/virology ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/physiopathology ; COVID-19/virology ; Female ; Humans ; Male ; Middle Aged ; Olfaction Disorders/diagnosis ; Olfaction Disorders/epidemiology ; Olfaction Disorders/physiopathology ; Olfaction Disorders/virology ; SARS-CoV-2/pathogenicity ; Smell/physiology
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2623587-0
ISSN	2162-3279 ; 2162-3279
ISSN (online)	2162-3279
ISSN	2162-3279
DOI	10.1002/brb3.2006
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Article ; Online: Subjective Perception of Recovery and Measured Olfactory Function in COVID-19 Patients.

Cancellieri, Emilia / Hernandez, Anna Kristina / Degkwitz, Helena / Kahre, Elisabeth / Blankenburg, Judith / Horst, Theresa S / Czyborra, Paula / Boscolo-Rizzo, Paolo / Hummel, Thomas

Viruses

2023 Volume 15, Issue 7

Abstract: ... of COVID-19 infection were included. Visual analogue scale (VAS) ratings for olfactory function ... to measured olfactory function after partial or complete subjective recovery in individuals with a history ... were determined. Participants were assigned to four "age groups" and three "recovery classes ...

Abstract	This cross-sectional study aimed to investigate self-rated olfactory dysfunction in relation to measured olfactory function after partial or complete subjective recovery in individuals with a history of coronavirus disease 2019 (COVID-19) infection. A total of 186 individuals (aged 5-62 years) with a history of COVID-19 infection were included. Visual analogue scale (VAS) ratings for olfactory function (before, during, and after infection) and age-appropriate psychophysical olfactory test scores (odor threshold and odor identification: "Sniffin' Sticks" for adults and both "Sniffin' Sticks" and "U-Sniff" for children) were determined. Participants were assigned to four "age groups" and three "recovery classes" (incomplete recovery, complete recovery, no smell loss). Surprisingly, there were no significant differences in odor threshold and adult identification scores between the "recovery classes". However, children with "incomplete recovery" had lower identification scores than those with "complete recovery" (
MeSH term(s)	Adult ; Humans ; Child ; Cross-Sectional Studies ; COVID-19 ; Sensory Thresholds ; Smell ; Olfaction Disorders/diagnosis ; Anosmia
Language	English
Publishing date	2023-06-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15071418
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Article ; Online: COVID-19 and olfactory dysfunction: a looming wave of dementia?

Kay, Leslie M

Journal of neurophysiology

2022 Volume 128, Issue 2, Page(s) 436–444

Abstract: ... longitudinal studies including cognitive and olfactory function from patients who have recovered from even mild COVID ... term olfactory dysfunction coupled with cognitive and emotional disturbance from COVID-19 may be ... Olfactory dysfunction is a hallmark symptom of COVID-19 disease resulting from the SARS-CoV-2 virus ...

Abstract	Olfactory dysfunction is a hallmark symptom of COVID-19 disease resulting from the SARS-CoV-2 virus. The cause of the sudden and usually temporary anosmia that most people suffer from COVID-19 is likely entirely peripheral-inflammation and other damage caused by the virus in the sensory epithelium inside the upper recesses of the nasal cavity can damage or prevent chemicals from properly activating the olfactory sensory neurons. However, persistent olfactory dysfunction from COVID-19, in the form of hyposmia and parosmia (decreased or altered smell) may affect as many as 15 million people worldwide. This epidemic of olfactory dysfunction is thus a continuing public health concern. Mounting evidence suggests that the SARS-CoV-2 virus itself or inflammation from the immune response in the nasal sensory epithelium may invade the olfactory bulb, likely via non-neuronal transmission. COVID-19-related long-term olfactory dysfunction and early damage to olfactory and limbic brain regions suggest a pattern of degeneration similar to that seen in early stages of Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Thus, long-term olfactory dysfunction coupled with cognitive and emotional disturbance from COVID-19 may be the first signs of delayed onset dementia from neurodegeneration. Few treatments are known to be effective to prevent further degeneration, but the first line of defense against degeneration may be olfactory and environmental enrichment. There is a pressing need for more research on treatments for olfactory dysfunction and longitudinal studies including cognitive and olfactory function from patients who have recovered from even mild COVID-19.
MeSH term(s)	Alzheimer Disease/complications ; COVID-19/complications ; Humans ; Inflammation ; Olfaction Disorders/epidemiology ; Olfaction Disorders/etiology ; Olfactory Bulb ; SARS-CoV-2 ; Smell
Language	English
Publishing date	2022-07-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00255.2022
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Article ; Online: Olfactory and neurological outcomes of SARS-CoV-2 from acute infection to recovery.

Desai, Deesha D / Yu, Sophie E / Salvatore, Brock / Goldberg, Zoe / Bowers, Eve M R / Moore, John A / Phan, BaDoi / Lee, Stella E

Frontiers in allergy

2022 Volume 3, Page(s) 1019274

Abstract: ... for the recovered group. Self-reported olfactory function and overall health metrics were also collected.: Results ... fashion with significant impact despite recovery from active infection. Although olfactory function ... patients influence sinonasal quality of life, olfactory function, and cognition.: Study design ...

Abstract	Educational objective: To investigate the impact of SARS-CoV-2 on sinonasal quality of life, olfaction, and cognition at different stages of viral infection and evaluate the association between olfaction and cognition in this population cohort. Objectives: While olfactory dysfunction (OD) is a frequently reported symptom of COVID-19 (98% prevalence), neurocognitive symptoms are becoming more apparent as patients recover from infection. This study aims to address how different stages of infection [active infection (positive PCR test, symptomatic) vs. recovered (7 days post-symptoms)] compared to healthy control patients influence sinonasal quality of life, olfactory function, and cognition. Study design: Prospective, longitudinal, case-control. Methods: Participants completed the SNOT-22, University of Pennsylvania Smell Identification Test (UPSIT) and validated cognitive examinations to assess degree of smell loss and neurocognitive function at baseline and at 1 and 3 months for the active group and 3 months for the recovered group. Self-reported olfactory function and overall health metrics were also collected. Results: The recovered group had the lowest average UPSIT score of 27.6 compared to 32.7 (active) and 32.6 (healthy control). 80% ( Conclusion: SARS-CoV-2 infection was found to impact olfactory function in a delayed fashion with significant impact despite recovery from active infection. Although olfactory function improved, decrements in cognitive processing speed were detected in our cohort.
Language	English
Publishing date	2022-10-26
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-6101
ISSN (online)	2673-6101
DOI	10.3389/falgy.2022.1019274
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Article: SARS-Cov-2 Cycle Threshold Value and Olfactory Dysfunction in COVID-19 Patients.

Goljanian Tabrizi, Ali / Mohseni Ashjerdi, Maliheh / Ghazizadeh, Matin / Maleki, Majid

Iranian journal of otorhinolaryngology

2023 Volume 35, Issue 130, Page(s) 263–273

Abstract: ... and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease 2019 (COVID-19 ... a significant factor not only in predicting OD severity in COVID-19 patients but also in the OD recovery ... respectively based on the UPSIT. The severity of COVID-19 and the rate of hospitalization were higher ...

Abstract	Introduction: Considering the inconsistent results regarding the association between the severity and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease 2019 (COVID-19) patients, we aimed to conduct this study. Materials and methods: This is a prospective cohort study in which COVID-19 patients were evaluated for the initial cycle threshold value (Ct values) measured by the nasopharyngeal samples along with olfactory function measured by the University of Pennsylvania Smell Identification Test (UPSIT) within 2 months of COVID-19 onset. Results: Among 309 COVID-19 patients who were included in this study, 108 (34.9%), 112 (36.2%) and 89 (28.8%) were normosmic, hyposmic, and anosmic, respectively based on the UPSIT. The severity of COVID-19 and the rate of hospitalization were higher in anosmic patients (p<0.0001, and p<0.0001, respectively). Moreover, significant associations between the initial Ct value and the severity of OD at admission and follow-ups were detected (p<0.0001 and p<0.0001, respectively). Anosmic patients had higher Ct values in comparison with hyposmic (approx. 3-fold) and normosmic (approx. 12-fold) patients. The recovery rate after one- and two-month follow-ups was 47% and 84%, respectively. At the follow-ups, OD-recovered patients significantly had lower Ct values (mean Ct value: 27.79 ± 2 and 28.21 ± 2.08) in comparison with those who have not recovered yet (mean Ct value: 30.19 ± 3.36, and 33.6 ± 3.37) (p<0.0001, and p<0.0001, respectively). Conclusions: Ct value seems to be a significant factor not only in predicting OD severity in COVID-19 patients but also in the OD recovery duration. This finding may be helpful to investigate the underlying mechanisms of OD in COVID-19 patients.
Language	English
Publishing date	2023-12-11
Publishing country	Iran
Document type	Journal Article
ZDB-ID	3018470-8
ISSN	2251-726X ; 2251-7251
ISSN (online)	2251-726X
ISSN	2251-7251
DOI	10.22038/IJORL.2023.71462.3429
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Article: Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Di Stadio, Arianna / Bernitsas, Evanthia / La Mantia, Ignazio / Brenner, Michael J / Ralli, Massimo / Vaira, Luigi Angelo / Colizza, Andrea / Cavaliere, Carlo / Laudani, Matteo / Frohman, Teresa C / De Vincentiis, Marco / Frohman, Elliot M / Altieri, Marta

Life (Basel, Switzerland)

2023 Volume 13, Issue 1

Abstract: ... with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and ... achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying ... to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included ...

Abstract	Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13010226
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Article ; Online: Therapeutic Efficacy of Nasal Corticosteroids in COVID-19-Related Olfactory Dysfunction: A Comprehensive Systematic Review and Meta-analysis.

Chen, Ru-Dong / Yang, Cong-Wen / Chen, Xiao-Bin / Hu, Hai-Feng / Cui, Guan-Zheng / Zhu, Qing-Run / Kuang, Ming-Jie

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

2023 Volume 170, Issue 4, Page(s) 999–1008

Abstract: ... corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies ... treatment, and olfactory recovery time.: Results: Seven studies involving 930 patients were analyzed ... Objective: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19 ...

Abstract	Objective: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. Data sources: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. Review methods: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. Results: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. Conclusion: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.
MeSH term(s)	Humans ; Rhinitis/drug therapy ; COVID-19/complications ; Adrenal Cortex Hormones/therapeutic use ; Steroids ; Olfaction Disorders/drug therapy ; Olfaction Disorders/etiology
Chemical Substances	Adrenal Cortex Hormones ; Steroids
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	392085-9
ISSN	1097-6817 ; 0161-6439 ; 0194-5998
ISSN (online)	1097-6817
ISSN	0161-6439 ; 0194-5998
DOI	10.1002/ohn.621
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Article ; Online: Post-viral effects of COVID-19 in the olfactory system and their implications.

Xydakis, Michael S / Albers, Mark W / Holbrook, Eric H / Lyon, Dina M / Shih, Robert Y / Frasnelli, Johannes A / Pagenstecher, Axel / Kupke, Alexandra / Enquist, Lynn W / Perlman, Stanley

The Lancet. Neurology

2021 Volume 20, Issue 9, Page(s) 753–761

Abstract: ... chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after ... to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has ... The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate ...

Abstract	Background: The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. Recent developments: The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. WHERE NEXT?: The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.
MeSH term(s)	Brain/diagnostic imaging ; Brain/physiopathology ; Brain/virology ; COVID-19/complications ; COVID-19/diagnostic imaging ; COVID-19/physiopathology ; Humans ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/physiopathology ; Olfaction Disorders/diagnostic imaging ; Olfaction Disorders/etiology ; Olfaction Disorders/physiopathology ; Olfaction Disorders/virology ; Olfactory Mucosa/diagnostic imaging ; Olfactory Mucosa/physiopathology ; Olfactory Mucosa/virology ; Prospective Studies ; Smell/physiology
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2081241-3
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(21)00182-4
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Article ; Online: Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

O'Byrne, Lisa / Webster, Katie E / MacKeith, Samuel / Philpott, Carl / Hopkins, Claire / Burton, Martin J

The Cochrane database of systematic reviews

2021 Volume 7, Page(s) CD013876

Abstract: Background: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection ... on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection ... on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction ...

Abstract	Background: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). Objectives: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. Selection criteria: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. Data collection and analysis: We used standard Cochrane methodological procedures. 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 one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). 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 other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.
MeSH term(s)	Administration, Oral ; Ambroxol/administration & dosage ; Betamethasone/administration & dosage ; Bias ; COVID-19/complications ; Expectorants/administration & dosage ; Glucocorticoids/administration & dosage ; Humans ; Nasal Decongestants/administration & dosage ; Nasal Lavage/methods ; Olfaction Disorders/drug therapy ; Olfaction Disorders/etiology ; Prednisone/administration & dosage ; Prevalence ; Quality of Life ; Recovery of Function ; Smell/drug effects ; Time Factors
Chemical Substances	Expectorants ; Glucocorticoids ; Nasal Decongestants ; Ambroxol (200168S0CL) ; Betamethasone (9842X06Q6M) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2021-07-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	1469-493X
ISSN (online)	1469-493X
DOI	10.1002/14651858.CD013876.pub2
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Article ; Online: Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results.

D'Ascanio, L / Vitelli, F / Cingolani, C / Maranzano, M / Brenner, M J / Di Stadio, A

European review for medical and pharmacological sciences

2021 Volume 25, Issue 11, Page(s) 4156–4162

Abstract: ... to support recovery of olfaction in COVID-19 patients.: Patients and methods: We conducted a randomized ... with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after ... rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory ...

Abstract	Objective: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients. Patients and methods: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment. Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection. Results: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender. Conclusions: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.
MeSH term(s)	Adult ; Amides/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Antiviral Agents/administration & dosage ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/drug therapy ; Drug Therapy, Combination ; Ethanolamines/administration & dosage ; Female ; Humans ; Luteolin/administration & dosage ; Male ; Middle Aged ; Olfaction Disorders/diagnosis ; Olfaction Disorders/drug therapy ; Olfaction Disorders/etiology ; Palmitic Acids/administration & dosage ; Pilot Projects ; Single-Blind Method ; Smell/drug effects ; Smell/physiology
Chemical Substances	Amides ; Anti-Inflammatory Agents, Non-Steroidal ; Antiviral Agents ; Ethanolamines ; Palmitic Acids ; palmidrol (6R8T1UDM3V) ; Luteolin (KUX1ZNC9J2)
Language	English
Publishing date	2021-06-22
Publishing country	Italy
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	605550-3
ISSN	2284-0729 ; 1128-3602 ; 0392-291X
ISSN (online)	2284-0729
ISSN	1128-3602 ; 0392-291X
DOI	10.26355/eurrev_202106_26059
Database	MEDical Literature Analysis and Retrieval System OnLINE

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