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.

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

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.

Prevalence of olfactory and taste dysfunction in COVID-19 patients: a community care facility study.

PURPOSE: We aim to study the prevalence of olfactory and taste dysfunction (OTD) in subjects residing in a Community Care Facility (CCF), a center unique to Singapore that is dedicated to isolate foreign workers with COVID-19 infection who have mild disease with minimal or no symptoms. METHODS: This is a cross-sectional study analyzing data prospectively collected from COVID-19-positive subjects who were admitted into a single-center Singapore EXPO CCF from 1st May 2020 to 1st July 2020. The following variables were collected: age, gender, ethnicity, anosmia, ageusia and acute respiratory infection (ARI) symptoms. Symptoms of anosmia and ageusia were self-declared via a mandatory questionnaire administered on admission. RESULTS: A total of 1983 subjects were included. The overall prevalence of anosmia and ageusia is 3.0% and 2.6%, respectively. 58% of anosmic subjects have co-existent ageusia and 72.6% of anosmic subjects have no concurrent sinonasal symptoms. OTD is less likely to present in subjects who are asymptomatic for ARI, compared to those symptomatic for ARI (anosmia: 2.0% versus 4.4% p = 0.002; ageusia: 1.6% versus 4.2% p < 0.001). There is a difference in the prevalence of OTD between the different ethnic groups (Indian, Chinese, Bangladeshi and Others), with Chinese and Bangladeshi reporting a higher prevalence (p < 0.043) CONCLUSION: The true prevalence of OTD in COVID-19-positive subjects may be low with aggressive screening of all subjects, including those asymptomatic for ARI.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

The accuracy of healthcare worker versus self collected (2-in-1) Oropharyngeal and Bilateral Mid-Turbinate (OPMT) swabs and saliva samples for SARS-CoV-2.

BACKGROUND: Self-sampling for SARS-CoV-2 would significantly raise testing capacity and reduce healthcare worker (HCW) exposure to infectious droplets personal, and protective equipment (PPE) use. METHODS: We conducted a diagnostic accuracy study where subjects with a confirmed diagnosis of COVID-19 (n = 401) and healthy volunteers (n = 100) were asked to self-swab from their oropharynx and mid-turbinate (OPMT), and self-collect saliva. The results of these samples were compared to an OPMT performed by a HCW in the same patient at the same session. RESULTS: In subjects confirmed to have COVID-19, the sensitivities of the HCW-swab, self-swab, saliva, and combined self-swab plus saliva samples were 82.8%, 75.1%, 74.3% and 86.5% respectively. All samples obtained from healthy volunteers were tested negative. Compared to HCW-swab, the sensitivities of a self-swab sample and saliva sample were inferior by 8.7% (95%CI: 2.4% to 15.0%, p = 0.006) and 9.5% (95%CI: 3.1% to 15.8%, p = 0.003) respectively. The combined detection rate of self-swab and saliva had a sensitivity of 2.7% (95%CI: -2.6% to 8.0%, p = 0.321). The sensitivity of both the self-collection methods are higher when the Ct value of the HCW swab is less than 30. The specificity of both the self-swab and saliva testing was 100% (95% CI 96.4% to 100%). CONCLUSION: Our study provides evidence that sensitivities of self-collected OPMT swab and saliva samples were inferior to a HCW swab, but they could still be useful testing tools in the appropriate clinical settings.

Adaptations of a Tertiary Otorhinolaryngology Head and Neck Surgery Department in Singapore during the COVID-19 Outbreak.

PURPOSE: The novel coronavirus 2019 (COVID-19) outbreak which was first reported in Wuhan, China has been declared a pandemic by the World Health Organization on March 11, 2020. Otorhinolaryngologists deal intimately with pathologies of the head and neck region and upper respiratory tract and have been reported as a vulnerable group of healthcare workers who may be more susceptible to COVID-19 nosocomial infection. METHODS: In this article, we provide a comprehensive overview of the adaptations of Singapore's largest tertiary Otorhinolaryngology department during the COVID-19 outbreak. This was undertaken via an evidence-based approach. The relevant medical literature and evidence underlying our adaptations are highlighted. RESULTS: A four-pronged strategy including (1) personnel segregation, (2) triaging and decantment, (3) use of personal protective equipment and (4) changes in clinical practice was employed. The strategy was bolstered by drawing upon a collective learnt experience from the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. CONCLUSION: A rigorous framework which can preserve operationality while navigating the heightened risks during this outbreak is critical for every Otorhinolaryngology department. As the pandemic continues to evolve and more scientific reports of this disease are made available, approaches will need to be morphed.

Respiratory sampling for severe acute respiratory syndrome coronavirus 2: An Overview.

The novel coronavirus disease 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was declared a pandemic in March 2020. A plethora of respiratory sampling methods for SARS-CoV-2 viral detection has been used and in the current evolving situation, there is no international consensus on the recommended method of respiratory sampling for diagnosis. Otolaryngologists deal intimately with the upper respiratory tract and a clear understanding of the respiratory sampling methods is of paramount importance. This article aims to provide an overview of the various methods and their evidence till date.