Olfactory and gustatory disturbances as a clinical presentation of coronavirus disease 2019 (COVID-19) infection in Malaysia – A nationwide multicentre case-control study

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, diarrhea, 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 the 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), the 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 answer an online questionnaire to evaluate and characterize their olfactory and taste symptoms. This is the same questionnaire that is answered by the COVID-19 patients in case cohort.

Observational, Retrospective Case-Control

This study population will draw subjects from the cohort in Phase 1 of the Malaysian COVID-19 Anosmia Study (Nationwide Multicentre Cross-Sectional Study) as cases. These cases will comprise adult patients with laboratory-confirmed COVID-19 infection from participating Malaysian hospital sites in this study, since the arrival of COVID-19 infection in Malaysia (January 2020) until present time.

The control subjects will be age and sex-matched healthy volunteers recruited from participating hospital sites in this study.

Primary Outcome Measures  :

1. Presence or absence of olfactory and taste disturbances in study participants
2. Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection 
3. 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.

Secondary Outcome Measures  :

1. Clinical manifestations of study participants [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
2. Other symptoms when diagnosed with COVID-19/within the past 2 weeks of answering the questionnaire
3. Other pre-existing health conditions [ Time Frame: Baseline ]
4. Positive predictive value (PPV) of olfactory and taste disturbances
5. Negative predictive value (NPV) of olfactory and taste disturbances
6. Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
7. The percentage of true positives, i.e. the proportion of patients with olfactory and taste disorders with COVID-19 infection. 
8. Specificity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
9. The percentage of true negatives, i.e. the proportion of patients without olfactory and taste disorders who do not have COVID-19 infection.

Clinical Trial.gov details

Monitoring & Evaluation
Vulnerable Populations

May 2020 — Aug 2020

Malaysia

Clinical Epidemiology of COVID-19 in Malaria Settings