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Inflammopharmacology Dec 2022There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying biological mechanisms and the role of inflammatory markers are still poorly understood.
AIM
To investigate the inflammatory biomarkers levels in patients with COVID-19 presenting chemosensory dysfunctions.
METHODS
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was performed from January 1, 2020, to May 12, 2022. Observational studies that provided data on hematological, biochemical, infection-related indices and cellular immunity, and coagulation function in patients with COVID-19 experiencing smell and/or taste disorders were considered eligible. Effect sizes were reported as standardized mean difference (SMD) with 95% confidence intervals (CI). A negative effect size indicated that the inflammatory biomarker levels were lower among patients with chemosensory dysfunctions.
RESULTS
Eleven studies were included. Patients with chemosensory disturbances had lower levels of leukocytes (SMD - 0.18, 95% CI - 0.35 to - 0.01, p = 0.04), lactate dehydrogenase (SMD - 0.45, 95% CI - 0.82 to - 0.09, p = 0.01), IL-6 (SMD - 0.25, 95% CI - 0.44 to - 0.06, p < 0.01), and C-reactive protein (SMD - 0.33, 95% CI - 0.58 to - 0.08, p < 0.01) than patients without chemosensory disturbances.
CONCLUSION
Patients with SARS-CoV-2 infection who have olfactory and gustatory disorders have a lower inflammatory response than patients who do not have chemosensory alterations. The presence of these symptoms may indicate a more favorable clinical course for COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Olfaction Disorders; Taste Disorders; Skin Diseases; Biomarkers
PubMed: 36097300
DOI: 10.1007/s10787-022-01066-z -
Frontiers in Medicine 2022Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the...
UNLABELLED
Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total 4,707; median per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7-16.6%), hyposmia 29.9% (95% CI 19.9-40%), ageusia 11.7% (95% CI 6.1-17.3%), and hypogeusia 31.2% (95% 16.4-46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms.
SYSTEMATIC REVIEW REGISTRATION
[www.crd.york.ac.uk/prospero], identifier [CRD42021292804].
PubMed: 36091707
DOI: 10.3389/fmed.2022.980253 -
Neuropsychology Review Dec 2023Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) were reviewed for studies investigating olfactory dysfunction in persons with moderate to severe TBI. Of the 5,223 studies reviewed, 19 met our inclusion criteria for the systematic review and 11 met inclusion criteria for meta-analysis. We calculated effect sizes (Hedges' g) to characterize the degree of olfactory dysfunction between patients with moderate to severe TBI and controls.
RESULTS
A total of 951 moderate-severe TBI patients from 19 studies were included in the systematic review, which largely demonstrated poorer olfactory psychophysical performances in this patient population. Meta-analysis demonstrated a large effect size for olfactory dysfunction in moderate-severe TBI relative to healthy controls (g=-2.43, 95%CI: -3.16 < δ<-1.69). The magnitude of the effect was moderated by age and patient sex, with larger effect sizes associated with older age (following exclusion of a pediatric population) and larger compositions of women in the patient group.
CONCLUSION
Moderate to severe TBI is associated with prominent olfactory dysfunction. Significant research gaps remain regarding the mechanism, recovery and natural history of olfactory dysfunction following moderate to severe TBI, which has significant clinical implications for the identification and treatment for those with post-traumatic olfactory dysfunction.
Topics: Humans; Child; Female; Olfaction Disorders; Brain Injuries, Traumatic; Smell
PubMed: 36070126
DOI: 10.1007/s11065-022-09563-2 -
The Cochrane Database of Systematic... Sep 2022Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in... (Review)
Review
BACKGROUND
Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. This is an update of the 2021 review with four studies added.
OBJECTIVES
1) To evaluate the benefits and harms of any intervention versus no treatment for people with acute 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, which had been present for less than 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 presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life 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 five studies with 691 participants. The studies evaluated the following interventions: intranasal corticosteroid sprays, intranasal corticosteroid drops, intranasal hypertonic saline and zinc sulphate. Intranasal corticosteroid spray compared to no intervention/placebo We included three studies with 288 participants who had olfactory dysfunction for less than four weeks following COVID-19. Presence of normal olfactory function The evidence is very uncertain about the effect of intranasal corticosteroid spray on both self-rated recovery of olfactory function and recovery of olfactory function using psychophysical tests at up to four weeks follow-up (self-rated: risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; psychophysical testing: RR 2.3, 95% CI 1.16 to 4.63; 1 study; 77 participants; very low-certainty evidence). Change in sense of smell The evidence is also very uncertain about the effect of intranasal corticosteroid spray on self-rated change in the sense of smell (at less than 4 weeks: mean difference (MD) 0.5 points lower, 95% CI 1.38 lower to 0.38 higher; 1 study; 77 participants; at > 4 weeks to 3 months: MD 2.4 points higher, 95% CI 1.32 higher to 3.48 higher; 1 study; 100 participants; very low-certainty evidence, rated on a scale of 1 to 10, higher scores mean better olfactory function). Intranasal corticosteroids may make little or no difference to the change in sense of smell when assessed with psychophysical testing (MD 0.2 points, 95% CI 2.06 points lower to 2.06 points higher; 1 study; 77 participants; low-certainty evidence, 0- to 24-point scale, higher scores mean better olfactory function). Serious adverse effects The authors of one study reported no adverse effects, but their intention to collect these data was not pre-specified so we are uncertain if these were systematically sought and identified. The remaining two studies did not report on adverse effects. Intranasal corticosteroid drops compared to no intervention/placebo We included one study with 248 participants who had olfactory dysfunction for ≤ 15 days following COVID-19. Presence of normal olfactory function Intranasal corticosteroid drops may make little or no difference to self-rated recovery at > 4 weeks to 3 months (RR 1.00, 95% CI 0.89 to 1.11; 1 study; 248 participants; low-certainty evidence). No other outcomes were assessed by this study. Data on the use of hypertonic saline nasal irrigation and the use of zinc sulphate to prevent persistent olfactory dysfunction are included in the full text of the review.
AUTHORS' CONCLUSIONS
There is very limited evidence available on the efficacy and harms of treatments for preventing 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.
Topics: Adrenal Cortex Hormones; COVID-19; Chronic Disease; Humans; Olfaction Disorders; Randomized Controlled Trials as Topic; Rhinitis; Smell; Zinc Sulfate
PubMed: 36063364
DOI: 10.1002/14651858.CD013877.pub3 -
The Cochrane Database of Systematic... Sep 2022Olfactory 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... (Review)
Review
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 intranasal 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 unable 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.
Topics: Adrenal Cortex Hormones; Anosmia; COVID-19; Expectorants; Humans; Luteolin; Nasal Decongestants; Randomized Controlled Trials as Topic; Smell
PubMed: 36062970
DOI: 10.1002/14651858.CD013876.pub3 -
American Journal of Rhinology & Allergy Jan 2023Nearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based... (Review)
Review
BACKGROUND
Nearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based review summarizes the evolving literature and offers recommendations for the clinician on the management of patients experiencing parosmia associated with COVID-19.
METHODS
We performed a systematic search using independent queries in PubMed, Embase, Ovid, and Cochrane databases, then categorized articles according to themes that emerged regarding epidemiology, effect on quality of life, disease progression, prognosis, pathophysiology, diagnosis, and treatment of parosmia.
RESULTS
We identified 123 unique references meeting eligibility and performed title and abstract review with 2 independent reviewers, with 74 articles undergoing full-text review. An inductive approach to thematic development provided 7 central themes regarding qualitative olfactory dysfunction following COVID-19.
CONCLUSIONS
While other respiratory viruses are known to cause qualitative olfactory disturbances, the incidence of parosmia following COVID-19 is notable, and correlates negatively with age. The presence of parosmia predicts persistent quantitative olfactory dysfunction. Onset can occur months after infection, and symptoms may persist for well over 7 months. Affected patients report increased anxiety and decreased quality of life. Structured olfactory training with essential oils is the preferred treatment, where parosmia predicts recovery of aspects of quantitative smell loss when undergoing training. There is limited evidence that nasal corticosteroids may accelerate recovery of olfactory function. Patients should be prepared for the possibility that symptoms may persist for years, and providers should guide them to resources for coping with their psychosocial burden.
Topics: Humans; Anosmia; COVID-19; Olfaction Disorders; Quality of Life; SARS-CoV-2; Smell
PubMed: 35957578
DOI: 10.1177/19458924221120117 -
BMJ (Clinical Research Ed.) Jul 2022To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.
REVIEW METHODS
Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery.
MAIN OUTCOME MEASURES
The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste.
RESULTS
18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I=70%, τ=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I=67%, τ=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I=0.0-77.2%, τ=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I=0.0-72.1%, τ=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I=20%, τ=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I=78%, τ=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I=10%, τ<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I=0%, τ<0.001) were less likely to recover their sense of smell.
CONCLUSIONS
A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021283922.
Topics: COVID-19; Female; Humans; Olfaction Disorders; Prognosis; Smell; Taste; Taste Disorders; Post-Acute COVID-19 Syndrome
PubMed: 35896188
DOI: 10.1136/bmj-2021-069503 -
Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
European Review For Medical and... Jun 2022The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, a viral outbreak that started in December 2019, eventually lead to a worldwide...
OBJECTIVE
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, a viral outbreak that started in December 2019, eventually lead to a worldwide pandemic. COVID-19 usually presents with flu-like symptoms, such as headaches, dry cough, fever, fatigue, myalgia, shortness of breath, diarrhea and loss of smell or taste. However, it can also have major effects on the cardiovascular system. Based on the available relevant literature, we aimed to elaborate the possible mechanisms influencing cardiovascular damage, myocardial injury and thromboembolic disease process in particular.
MATERIALS AND METHODS
After considering our inclusion and exclusion criteria, the systematic review included 8 studies in total.
RESULTS
In general, underlying cardiovascular diseases were associated with poorer clinical outcomes. This may be due to immunological dysregulation. The disease outcomes were also positively correlated with the severity of the disease, especially with myocardial injury. Thus, cardiac biomarkers, such as Troponin T, CK-MB and myoglobin could be utilized in prediction algorithms for deciphering the clinical outcome in COVID-19 patients.
CONCLUSIONS
Venous thromboembolisms were commonly encountered complications despite the administration of thromboprophylaxis, and they mostly presented as pulmonary embolisms, warranting the need for relevant investigations in hemodynamically unstable patients. However, more studies need to be conducted to better understand the mechanisms at play and the ensuing complications, to better treat COVID-19 patients.
Topics: Anticoagulants; COVID-19; Humans; SARS-CoV-2; Troponin T; Venous Thromboembolism
PubMed: 35776052
DOI: 10.26355/eurrev_202206_29090 -
Acta Otorhinolaryngologica Italica :... Apr 2022The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging...
OBJECTIVE
The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID".
METHODS
The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2.
RESULTS
1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021.
CONCLUSIONS
The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.
Topics: COVID-19; Hearing Disorders; Humans; Olfaction Disorders; SARS-CoV-2; Taste Disorders; Vertigo; Post-Acute COVID-19 Syndrome
PubMed: 35763279
DOI: 10.14639/0392-100X-suppl.1-42-2022-10