COVID-19 Anosmia: High Prevalence, Plural Neuropathogenic Mechanisms, and Scarce Neurotropism of SARS-CoV-2?

Liang, Fengyi; Wang, De Yun

doi:10.3390/v13112225

Cited by 32 publications

(57 citation statements)

References 131 publications

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“… 56 SARS-CoV-2 infects and eliminates most olfactory epithelial support (sustentacular) cells that express angiotensin converting enzyme-2, which leads to olfactory neuron deciliation and necrosis. 55 57 Varying regeneration speed of support cells and sensory neurons, influenced by the degree of inflammation, could explain the delayed smell recovery. Stem cell damage and severe inflammation may also prolong smell dysfunction by slowing the regeneration of olfactory epithelial.…”

Section: Discussionmentioning

confidence: 99%

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves

Tan

Han

Zhao

et al. 2022

BMJ

142

131

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ObjectiveTo 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.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.Review methodsTwo 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 synthesisTwo 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 measuresThe 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.Results18 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%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=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 (I2=0.0-77.2%, τ2=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 I2=0.0-72.1%, τ2=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, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell.ConclusionsA 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 registrationPROSPERO CRD42021283922.

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Section: Discussionmentioning

confidence: 99%

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves

Tan

Han

Zhao

et al. 2022

BMJ

142

131

View full text Add to dashboard Cite

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“…It has not yet been clarified what the frequency of persistent disturbances is in these groups of individuals, but if the prevalence recorded in cases of primary infection were confirmed, it would mean that this problem may not end with the immunization of the population. Second, the identification of the pathogenesis [54][55][56][57][58][59][60][61] and risk factors [2][3][4][5][6][7][8][9][10][11][12][62][63][64][65][66][67][68] for the development of persistent CD are in its infancy. For this reason, no effective therapies have yet been found for the prevention and treatment of COVID-19 related POD and PGD [69][70][71][72][73][74][75].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Persistent Olfactory and Gustatory Dysfunctions on Quality of Life in Long-COVID-19 Patients

Vaira

Gessa

Deiana

et al. 2022

Life

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(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

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“…At present, conductive mechanisms of olfactory loss in COVID‐19‐associated OD have largely been dismissed in favor of sensorineural mechanisms, 60 , 61 given the absence of significant sinonasal symptoms like nasal obstruction and mucosal congestion in COVID‐19 infection. 60 , 62 However, our findings suggest that conductive mechanisms may play a crucial role in mediating smell loss in 63% of patients.…”

Section: Discussionmentioning

confidence: 99%

Neuroradiological Basis of COVID‐19 Olfactory Dysfunction: A Systematic Review and Meta‐Analysis

Tan

et al. 2022

The Laryngoscope

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Objective Olfactory dysfunction (OD) is a common presenting symptom of COVID‐19 infection. Radiological imaging of the olfactory structures in patients with COVID‐19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention. Methods PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID‐19 infection and OD, following preferred reporting items for systematic reviews and meta‐analyses guidelines and a PROSPERO‐registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random‐effects meta‐analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID‐19‐associated OD. Results We included 7 case–control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID‐19 infection and OD (63%, 95% CI = 0.38–0.82) was significantly higher than that in controls (4%, 95% CI = 0.01–0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID‐19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes. Conclusion Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID‐19 patients. Laryngoscope, 132:1260–1274, 2022

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COVID-19 Anosmia: High Prevalence, Plural Neuropathogenic Mechanisms, and Scarce Neurotropism of SARS-CoV-2?

Cited by 32 publications

References 131 publications

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves

The Effects of Persistent Olfactory and Gustatory Dysfunctions on Quality of Life in Long-COVID-19 Patients

Neuroradiological Basis of COVID‐19 Olfactory Dysfunction: A Systematic Review and Meta‐Analysis

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