Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.
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ABSTRACT:
SUBMITTER: Webster KE
PROVIDER: S-EPMC8406518 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.
Webster Katie E KE O'Byrne Lisa L MacKeith Samuel S Philpott Carl C Hopkins Claire C Burton Martin J MJ
The Cochrane database of systematic reviews 20210722
<h4>Background</h4>Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected 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 prom ...[more]
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Project description:BackgroundOlfactory 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Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials.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 resultsWe 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' conclusionsThere 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.
| S-EPMC9443431 | biostudies-literature
Project description:BackgroundMagnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.MethodsThe main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.ResultsAll patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).ConclusionSystematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.
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Project description:ObjectiveThis research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19).MethodsCOVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores.ResultsForty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected).InterpretationThere is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients.
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| S-EPMC9707023 | biostudies-literature
Project description:Quantifying olfactory impairments can facilitate early detection of Coronavirus disease 2019 (COVID-19). Despite being a debated topic, many reports provide evidence for the neurotropism of SARS-CoV-2. However, a sensitive, specific, and accurate non-invasive method for quantifying persistent neurological impairments is missing to date. To quantify olfactory detectabilities and neurocognitive impairments in symptomatic COVID-19 patients during and post-infection periods, we used a custom-built olfactory-action meter (OAM) providing accurate behavioral readouts. Ten monomolecular odors were used for quantifying olfactory detectabilities and two pairs of odors were employed for olfactory matching tests. We followed cohorts of healthy subjects, symptomatic patients, and recovered subjects for probing olfactory learning deficits, before the Coronavirus Omicron variant was reported in India. Our method identifies severe and persistent olfactory dysfunctions in symptomatic patients during COVID-19 infection. Symptomatic patients and recovered subjects showed significant olfactory learning deficits during and post-infection periods, 4-18 months, in comparison to healthy subjects. On comparing olfactory fitness, we found differential odor detectabilities and olfactory function scores in symptomatic patients and asymptomatic carriers. Our results indicate probable long-term neurocognitive deficits in COVID-19 patients imploring the necessity of long-term tracking during post-infection period. Differential olfactory fitness observed in symptomatic patients and asymptomatic carriers demand probing mechanisms of potentially distinct infection routes.
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Project description:Persistent olfactory dysfunction (OD) is one of the most complaining and worrying complications of long COVID-19 because of the potential long-term neurological consequences. While causes of OD in the acute phases of the SARS-CoV-2 infection have been figured out, reasons for persistent OD are still unclear. Here we investigated the activity of two inflammatory pathways tightly linked with olfaction pathophysiology, namely Substance P (SP) and Prokineticin-2 (PK2), directly within the olfactory neurons (ONs) of patients to understand mechanisms of persistent post-COVID-19 OD. ONs were collected by non-invasive brushing from ten patients with persistent post-COVID-19 OD and ten healthy controls. Gene expression levels of SP, Neurokinin receptor 1, Interleukin-1β (IL-1β), PK2, PK2 receptors type 1 and 2, and Prokineticin-2-long peptide were measured in ONs by Real Time-PCR in both the groups, and correlated with residual olfaction. Immunofluorescence staining was also performed to quantify SP and PK2 proteins. OD patients, compared to controls, exhibited increased levels of both SP and PK2 in ONs, the latter proportional to residual olfaction. This work provided unprecedented, preliminary evidence that both SP and PK2 pathways may have a role in persistent post-COVID-19 OD. Namely, if the sustained activation of SP, lasting months after infection's resolution, might foster chronic inflammation and contribute to hyposmia, the PK2 expression could instead support the smell recovery.
| S-EPMC9760596 | biostudies-literature
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Project description:(1) Background: Persistent post-viral olfactory disorders (PPVOD) are estimated at 30% of patients one year after COVID-19 infection. No treatment is, to date, significantly effective on PPVOD with the exception of olfactory training (OT). The main objective of this work was to evaluate OT efficiency on post-COVID-19 PPVOD. (2) Methods: Consecutive patients consulting to the ENT department with post-COVID-19 PPVOD were included after completing clinical examination, the complete Sniffin’ Stick Test (TDI), the short version of the Questionnaire of olfactory disorders and the SF-36. Patients were trained to practice a self-olfactory training with a dedicated olfactory training kit twice a day for 6 months before returning to undergo the same assessments. (3) Results: Forty-three patients were included and performed 3.5 months of OT in average. We observed a significant TDI score improvement, increasing from 24.7 (±8.9) before the OT to 30.9 (±9.8) (p < 0.001). Based on normative data, a significant increase in the number of normosmic participants was observed only for the threshold values (p < 0.001). Specific and general olfaction-related quality of life improved after the OT. (4) Conclusions: Olfactory function appeared to improve only in peripheral aspects of post-COVID-19 PPVOD after OT. Future controlled studies must be performed to confirm the OT role and justify new therapeutic strategies that may focus on the central aspects of post-COVID-19 PPVOD.
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