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

AbstractObjectiveTo 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, Coch...

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Veröffentlicht in:BMJ. British medical journal (Clinical research ed.) Jg. 378; S. e069503
Hauptverfasser: Tan, Benjamin Kye Jyn, Han, Ruobing, Zhao, Joseph J, Tan, Nicole Kye Wen, Quah, Emrick Sen Hui, Tan, Claire Jing-Wen, Chan, Yiong Huak, Teo, Neville Wei Yang, Charn, Tze Choong, See, Anna, Xu, Shuhui, Chapurin, Nikita, Chandra, Rakesh K, Chowdhury, Naweed, Butowt, Rafal, von Bartheld, Christopher S, Kumar, B Nirmal, Hopkins, Claire, Toh, Song Tar
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England British Medical Journal Publishing Group 27.07.2022
BMJ Publishing Group LTD
Schlagworte:
Bias
Confidence intervals
Coronaviruses
COVID-19
COVID-19 - complications
Female
Humans
Long COVID
Medical prognosis
Meta-analysis
Observational studies
Olfaction
Olfaction Disorders - etiology
Patients
Post-Acute COVID-19 Syndrome
Prognosis
Recovery (Medical)
Sensitivity analysis
Severe acute respiratory syndrome coronavirus 2
Smell
Survival
Taste
Taste Disorders - etiology
ISSN:1756-1833, 1756-1833
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Zusammenfassung:AbstractObjectiveTo 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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ISSN:1756-1833
1756-1833
DOI:10.1136/bmj-2021-069503