Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis..., 2022, Toh et al

Abstract

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%, 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.

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.

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What jumped out at me is that women were half as likely to recover their sense of smell as men and one third as likely to recover their sense of taste as men in this meta-analysis. Perhaps this points to a shared underlying mechanism between ME-type Long Covid and loss of sense or smell or taste.

 

Here professor Janszky (a neurologist) keeps hinting at that. The UK Biobank found changes in areas connected to the olfactory cortex in people who had caught covid and so did he and he thinks that the affected areas in the orbitofrontal cortex might play a role in long covid somehow.

 

I used to have a very acute sense of smell and taste. They started deteriorating slowly after I gave up smoking in 2009, and at the same time I lost almost all of my saliva production. I'm sure these things are all connected. Taste and smell still worked moderately well before I got Covid in November 2021 and before that I mostly blamed ageing for what I'd lost. I lost both senses of smell and taste completely during Covid, and although they have recovered to a small extent they are really not a patch on what they were before Covid.

 

Apart from the finding that women were less likely to recover their sense of smell, the very wide confidence intervals and/or high heterogeneities (I2) unfortunately preclude from deriving accurate enough estimates and thus from making definitive conclusions.