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. Systematic review registration PROSPERO CRD42021283922.

/pdf/prognosis-and-persistence-of-smell-and-taste-dysfunction-in-ikaksbj7.pdf

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

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% confidence interval: 35.34%-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, P = 0.45). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Olfactory loss has been identified as one of the common symptoms related to COVID-19 infection. Although olfactory loss is recognized, our understanding of both the extent of loss and time to olfactory recovery following infection is less well known. Similarly, knowledge of potential impactful patient factors and therapies that influence olfactory recovery is desirable but is not overtly clear in the literature. Our systematic review sought to fill this knowledge gap. We included studies that: involved either an observational or an interventional design that reported data on patients with olfactory dysfunction due to Reverse Transcription Polymerase Chain Reaction (RT-PCR) diagnosed COVID-19 infection; and reported data regarding olfactory recovery measured by an objective olfactory test, Likert scale and/or visual analog scale (VAS). The study methods were determined a priori and registered in PROSPERO (Registration Number CRD42020204354). An information specialist searched Medline, Embase, LitCovid and the Cochrane Register of Controlled Trials up to March 2021, and two reviewers were involved in all aspects of study selection and data collection. After screening 2788 citations, a total of 44 studies of assorted observational designs were included. Patients had undergone objective COVID-19 testing, and most were adult patients with mild to moderate COVID-19. Olfactory recovery was found to occur as early as 7 days, with most patients recovering olfaction within 30 days. Few studies included prolonged follow-up to 6 months or longer duration. Poor olfaction at initial presentation was associated with poor recovery rates. Only a small number of studies assessed olfactory retraining and steroid therapy. Additional trials are underway.

Olfactory recovery following infection with COVID-19: A systematic review.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19, taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 241 meeting all inclusion criteria. Additionally, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct prevalence measures of taste loss would be the most valid because they avoid the taste/smell confusion of self-report. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% CI: 35.34-43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, p = 0.45). Generally, males reported lower rates of taste loss than did females and taste loss was highest in middle-aged groups. Thus, taste loss is a bona fide symptom COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

/pdf/taste-loss-as-a-distinct-symptom-of-covid-19-a-systematic-2quo7x1162.pdf

Taste loss as a distinct symptom of COVID-19: A systematic review and meta-analysis

Background and purpose The coronavirus disease 2019 (COVID-19) has been associated with olfactory dysfunction. The persistent symptoms of anosmia or hyposmia were associated in previous studies with the development of memory impairment and mood disturbances. We aimed to investigate the association between the chronicity of reported olfactory dysfunction and subjective and objective cognitive performance in long-COVID patients and to explore whether their emotional symptoms are related to their cognition. Methods One hundred twenty-eight long-COVID participants were recruited. Reported symptomatology, subjective memory complaints, anxiety and depression symptomatology, and trait-anxiety were assessed. Subjective memory complaints and mood disturbances were compared among groups of participants with olfactory dysfunction as an acute (AOD), persistent (POD), or nonexistent (NOD) symptom. Seventy-six of the volunteers also participated in a face-to-face session to assess their objective performance on tests of general cognitive function and verbal declarative memory. Objective cognitive performance and mood disturbances were compared among the AOD, POD, and NOD groups. Results The subjective memory complaints and the anxiety and depression symptoms were similar among the groups, but the score in general cognitive function was lower in the participants with symptoms of acute olfactory dysfunction than in those with no olfactory symptoms at any time. Participants’ memory complaints were positively related to their emotional symptoms. The relationship between depressive symptomatology and memory complaints interacted with the olfactory dysfunction, as it only occurred in the participants without symptoms of olfactory dysfunction. Depressive symptomatology and acute olfactory symptoms were negatively associated with general cognitive function and delayed memory performance. The months elapsed from diagnosis to assessment also predicted delayed memory performance. Anxious symptomatology was negatively associated with the immediate ability to recall verbal information in participants who did not present olfactory dysfunction in the acute phase of the infection. Conclusion Olfactory dysfunction in the acute phase of the infection by COVID-19 is related to cognitive deficits in objective tests, and mood disturbances are associated with self-reported and objective memory. These findings may contribute to further understanding the neuropsychological and emotional aspects of long-COVID.

/pdf/association-between-olfactory-dysfunction-and-mood-1zvs9a8h.pdf

Association between olfactory dysfunction and mood disturbances with objective and subjective cognitive deficits in long-COVID

BackgroundAnosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear.ObjectiveTo examine factors associated with ...

https://journals.sagepub.com/doi/pdf/10.1177/19458924211004800

COVID-19-Induced Anosmia and Ageusia Are Associated With Younger Age and Lower Blood Eosinophil Counts.

ObjectiveTo characterize the relationship between severity of sleep apnea and coronavirus disease 2019 (COVID-19) hospitalization and severe illness.Study DesignRetrospective cohort study.SettingMo...

https://journals.sagepub.com/doi/pdf/10.1177/2473974X211016283

Severity of Sleep Apnea and COVID-19 Illness

Loss of sense of smells associated with sour taste is a possible diagnostic marker for COVID-19

Tonsillectomy and poliomyelitis: Development of causality.

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Papers

COVID-19-Induced Anosmia and Ageusia Are Associated With Younger Age and Lower Blood Eosinophil Counts.

Severity of Sleep Apnea and COVID-19 Illness

Loss of sense of smells associated with sour taste is a possible diagnostic marker for COVID-19

Tonsillectomy and poliomyelitis: Development of causality.