Malaysian COVID-19 Anosmia Study (Phase 2) - A Nationwide Multicentre Case-Control Study

Study Overview
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Brief Summary
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The Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection. This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The case-control study is described here (the cross-sectional study is described in a separate ClinicalTrials.gov record).

Detailed Description
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The world is currently in the midst of the Coronavirus 2019 (COVID-19) pandemic that is caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). According to published cohort studies on COVID-29 infected patients, the most prevalent symptoms consist of fever, dry cough, dyspnoea, sputum production, myalgia, arthralgia, headache, diarrhoea, and sore throat. Recently, there have been concerns of significant viral transmission through asymptomatic, pre-symptomatic or even mildly symptomatic patients. There is increasing anecdotal evidence from patients and healthcare professionals highlighting isolated loss of sense of smell (anosmia) and taste disturbances (dysgeusia) as atypical symptoms of COVID-19 infection in otherwise asymptomatic patients. In parallel, expert statements from the British Association of Otorhinolaryngology-Head & Neck Surgery (ENT UK), British Rhinological Society, and the American Association of Otolaryngology-Head & Neck Surgery (AAO-HNS) have suggested that olfactory and taste disturbances could be a clinical feature of COVID-19 infection. Rapidly emerging evidence from Europe, the United Kingdom and the United States have found olfactory and taste disturbances to be highly prevalent in patients diagnosed with COVID-19. In contrast, there is currently limited evidence from Asia on the prevalence of these symptoms in COVID-19 infection. Additionally, there is also limited evidence on the predictive value of screening for olfactory and taste disturbance in COVID-19 patients with subclinical symptoms. The aim of this case-control study is to study the predictive value of screening for olfactory and taste disturbance in patients with COVID-19 infection in Malaysia. The cases will be selected from the cohort of COVID-19 positive patients recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country (from Phase 1 of the Malaysian COVID-19 Anosmia Study). Controls will be recruited from healthy volunteers who will will answer the an online questionnaire to evaluate and characterise their olfactory and taste symptoms. This is the same questionnaire that is answered by the COVID-19 patients in case cohort.

Official Title
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Olfactory and Gustatory Disturbances as a Clinical Presentation of Coronavirus Disease 2019 (COVID-19) Infection in Malaysia - A Nationwide Multicentre Case-Control Study

Conditions
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SARS-CoV Infection, COVID-19, Anosmia, Dysgeusia

Intervention / Treatment
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* Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at least 18 years old For Cases: Laboratory confirmed COVID-19 infection [Reverse Transcription Polymerase Chain Reaction (RT-PCR)] Patients clinically able to answer the questionnaire Exclusion Criteria: Patients with olfactory or taste/gustatory disorders before the COVID-19 epidemic For Cases: Patients without a laboratory-confirmed COVID-19 diagnosis For Cases: Patients in intensive care unit at the time of study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Malaysian COVID-19 Cohort (Cases)<br>A cohort of COVID-19 positive patients will be recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country. | Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances<br>* This is an online patient-reported questionnaire that examines the presence or absence of olfactory and taste disturbances, the onset of olfactory and taste disturbances in relation to other COVID-19 symptoms, and the temporal evolution of the severity of olfactory and taste disturbances. The occurrence of ear symptoms in COVID-19 infection will also be evaluated in this questionnaire as a secondary outcome. The questionnaire will also have questions relating to the patient's underlying health conditions, risk factors for COVID-19 infection, and demographics.<br>|
| Healthy Volunteers (Controls)<br>A cohort of age and sex-matched healthy volunteers will be recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country. | Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances<br>* This is an online patient-reported questionnaire that examines the presence or absence of olfactory and taste disturbances, the onset of olfactory and taste disturbances in relation to other COVID-19 symptoms, and the temporal evolution of the severity of olfactory and taste disturbances. The occurrence of ear symptoms in COVID-19 infection will also be evaluated in this questionnaire as a secondary outcome. The questionnaire will also have questions relating to the patient's underlying health conditions, risk factors for COVID-19 infection, and demographics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or absence of olfactory and taste disturbances in study participants | In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances | 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection | 
| Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection | The relationship between case & control status and each exposure variable will be estimated by odds ratios and their 95% confidence intervals using conditional logistic regression models. | 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical manifestations of study participants | In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19/within the past 2 weeks of answering the questionnaire (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms) | 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection | 
| Other pre-existing health conditions | In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.) | Baseline | 
| Positive predictive value (PPV) of olfactory and taste disturbances in predicting diagnosis of COVID-19 infection | PPV reflects the probability that the presence of olfactory and taste disturbances will have a positive diagnosis of COVID-19. This is derived from dividing the number of patients with olfactory & taste disturbances with COVID-19 infection over the total number of patients with olfactory and taste disturbances, and multiplying by 100% | Baseline | 
| Negative predictive value (NPV) of olfactory and taste disturbances in predicting absence of COVID-19 infection | NPV reflects the probability that the absence of olfactory and taste disturbances will have a negative diagnosis of COVID-19. This is derived from dividing the number of patients without olfactory & taste disturbances and without COVID-19 infection over the total number of patients with no olfactory and taste disturbances, and multiplying by 100% | Baseline | 
| Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection | The percentage of true positives, i.e. the proportion of patients with olfactory and taste disorders with COVID-19 infection. This can be calculated by dividing the number of subjects with olfactory & taste disturbances who have COVID-19 infection with the number of patients with olfactory & taste disturbances, and multiplying by 100% | Baseline | 
| Specificity of olfactory and taste disturbances in predicting COVID-19 infection | The percentage of true negatives, i.e. the proportion of patients without olfactory and taste disorders who do not have COVID-19 infection. This can be calculated by dividing the number of subjects without olfactory & taste disturbances who do not have COVID-19 infection with the number of patients without olfactory & taste disturbances, and multiplying by 100% | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cross-sectional study, Prevalence, Otorhinolaryngology, Infectious Diseases, Anosmia, Dysgeusia, Olfactory Disorders, Taste Disorders, COVID-19, SARS-CoV-2, Coronavirus 2019