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

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.

Loss of smell and taste: a new marker of COVID-19? Tracking reduced sense of smell during the coronavirus pandemic using search trends.

OBJECTIVES: It has been demonstrated that reduction in smell and/or taste is the most predictive symptom in SARS-CoV-2/Covid-19 infection. We used Google Trends to analyze regional searches relating to loss of smell and taste across Italy, Spain, France, Brazil, and the United States of America and determined the association with reported Covid-19 cases. METHODS: In order to retrieve the data, we built a Python software program that provides access to Google Trends data via an application program interface. Daily COVID-19 case data for subregions of the five countries selected were retrieved from respective national health authorities. We sought to assess the association between raw search interest data and COVID-19 new daily cases per million for all regions individually. RESULTS: In total, we yielded 2188 sets of Google Trends data which included 548 time series of 4 anosmia and ageusia search concepts over the study period for 137 regions. These data indicated that differences in search interest for terms relating to anosmia and ageusia, between regions, is associated with geographical trends in new Covid-19 cases. CONCLUSIONS: We feel that Google search trends relating to loss of smell can be utilized to identify potential Covid-19 outbreaks on a national and regional basis.

Early recovery following new onset anosmia during the COVID-19 pandemic - an observational cohort study.

BACKGROUND: A rapidly evolving evidence suggests that smell and taste disturbance are common symptoms in COVID-19 infection. As yet there are no reports on duration and recovery rates. We set out to characterise patients reporting new onset smell and taste disturbance during the COVID-19 pandemic and report on early recovery rates. METHODS: Online Survey of patients reporting self-diagnosed new onset smell and taste disturbance during the COVID-19 pandemic, with 1 week follow-up. RESULTS: Three hundred eighty-two patents completed bot an initial and follow-up survey. 86.4% reported complete anosmia and a further 11.5% a very severe loss of smell at the time of completing the first survey. At follow-up 1 week later, there is already significant improvement in self-rating of severity of olfactory loss. 80.1% report lower severity scores at follow-up, 17.6% are unchanged and 1.9% are worse. 11.5% already report compete resolution at follow up, while 17.3% report persistent complete loss of smell, with reported duration being 1 to over 4 weeks. This is reflected in the overall cumulative improvement rate of 79% patients overall in the interval between surveys. CONCLUSIONS: A review of the growing evidence base supports the likelihood that out cohort have suffered olfactory loss as part of COVID-19 infection. While early recovery rates are encouraging, long term rates will need to be further investigated and there may be an increase in patients with persistent post-viral loss as a result of the pandemic. We further call for loss of sense of smell to be formerly recognised as a marker of COVID-19 infection.