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

• ClinicalTrials.gov Identifier: NCT04384042
• Recruitment Status: Unknown
• First Posted: May 12, 2020
• Last Update Posted: February 25, 2021
• Sponsor: Hospital Sultanah Bahiyah
• Collaborators: Hospital Tuanku Fauziah, Kangar, Perlis; Penang Hospital, Malaysia; Hospital Raja Permaisuri Bainun; Hospital Sungai Buloh, Selangor; Kuala Lumpur General Hospital; Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Hospital Melaka, Melaka; Hospital Enche Besar Hajjah Khalsom, Kluang, Johor; Hospital Raja Perempuan Zainab II, Kota Bahru, Kelantan; Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu; Hospital Tengku Ampuan Afzan, Kuantan, Pahang; Sarawak General Hospital; Hospital Queen Elizabeth, Malaysia
• Information provided by (Responsible Party): Siti Sabzah bt Mohd Hashim, MD, MS (ORL-HNS), Hospital Sultanah Bahiyah

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment
SARS-CoV Infection; COVID-19; Anosmia; Dysgeusia	Other: Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances

Detailed Description:

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 60 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Olfactory and Gustatory Disturbances as a Clinical Presentation of Coronavirus Disease 2019 (COVID-19) Infection in Malaysia - A Nationwide Multicentre Case-Control Study
• Actual Study Start Date: June 6, 2020
• Estimated Primary Completion Date: March 31, 2021
• Estimated Study Completion Date: March 31, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Malaysian COVID-19 Cohort (Cases); 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; 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.
Healthy Volunteers (Controls); 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Presence or absence of olfactory and taste disturbances in study participants [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
   In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
2. Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of 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.

Secondary Outcome Measures :

1. Clinical manifestations of study participants [ Time Frame: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infection ]
   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. Other pre-existing health conditions [ Time Frame: Baseline ]
   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.)
3. Positive predictive value (PPV) of olfactory and taste disturbances in predicting diagnosis of COVID-19 infection [ Time Frame: Baseline ]
   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%
4. Negative predictive value (NPV) of olfactory and taste disturbances in predicting absence of COVID-19 infection [ Time Frame: Baseline ]
   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%
5. Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
   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%
6. Specificity of olfactory and taste disturbances in predicting COVID-19 infection [ Time Frame: Baseline ]
   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%

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

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.

Criteria

Inclusion Criteria:

1. Age at least 18 years old
2. For Cases: Laboratory confirmed COVID-19 infection [Reverse Transcription Polymerase Chain Reaction (RT-PCR)]
3. Patients clinically able to answer the questionnaire

Exclusion Criteria:

1. Patients with olfactory or taste/gustatory disorders before the COVID-19 epidemic
2. For Cases: Patients without a laboratory-confirmed COVID-19 diagnosis
3. For Cases: Patients in intensive care unit at the time of study

Contacts and Locations

Contacts

Contact: Siti Sabzah Mohd Hashim, MD MS; +604 740 7335; dr_ctsabzah@yahoo.com

Contact: Shen-Han Lee, MB PhD MRCS; +6016 474 0088; shen-han.lee@cantab.net

Locations

Malaysia

Hospital Enche' Besar Hajjah Khalsom; Recruiting

Kluang, Johor, Malaysia, 86000

Contact: Jothi Shanmuganathan, MBBS MMed

Principal Investigator: Jothi Shanmuganathan, MBBS MMed

Sub-Investigator: Masliza Zaid, MBBS MMed

Principal Investigator: Tengku Mohamed Izam Tengku Kamalden, MD MS FRCS

Hospital Sultanah Bahiyah; Recruiting

Alor Setar, Kedah, Malaysia, 05400

Contact: Siti Sabzah Mohd Hashim, MD MS

Contact: Shen-Han Lee, MB PhD MRCS

Principal Investigator: Siti Sabzah Mohd Hashim, MD MS

Sub-Investigator: Norzi Gazali, MBBS MMed

Sub-Investigator: Ida Sadja'ah Sachlin, MBBS MMed

Sub-Investigator: Zhi Xiang Yeoh, MBBS MS MRCS

Sub-Investigator: Shen-Han Lee, MB PhD MRCS

Sub-Investigator: Lee Lee Low, MD MRCP

Sub-Investigator: Sharifah Baizura Syed Alwi, MD MRCPI

Sub-Investigator: Shahrul Aiman Soelar, B Ind Stats

Sub-Investigator: Ibtisam Ismail, BSc

Hospital Raja Perempuan Zainab II; Recruiting

Kota Bharu, Kelantan, Malaysia, 15200

Contact: Zulkiflee Salahuddin, MD MS

Principal Investigator: Zulkiflee Salahuddin, MD MS

Sub-Investigator: Rosdi Ramli, MBBS MMed

Sub-Investigator: Mahiran Mustafa, MBBCh MMed

Sub-Investigator: Anilawati Mat Jelani, MD MMed

Sub-Investigator: Rosli Mohd Noor, MD MMed

Hospital Tuanku Jaafar; Recruiting

Seremban, Negeri Sembilan, Malaysia, 70300

Contact: Jeyasakthy Saniasiaya, MMed FEBORL

Principal Investigator: Jeyasakthy Saniasiaya, MMed FEBORL

Sub-Investigator: Tiang Koi Ng, MBBS MRCP

Hospital Tengku Ampuan Afzan; Recruiting

Kuantan, Pahang, Malaysia, 25100

Contact: Suhaimi Yusuf, MBBS MMed

Principal Investigator: Suhaimi Yusof, MBBS MMed

Sub-Investigator: Dzawani Muhamad, MD MMed

Penang Hospital; Recruiting

George Town, Penang, Malaysia, 10990

Contact: Chenthilnathan Periasamy, MBBS MMed

Principal Investigator: Chenthilnathan Periasamy, MBBS MMed

Sub-Investigator: Ting Soo Chow, MD MRCP

Hospital Raja Permaisuri Bainun; Recruiting

Ipoh, Perak, Malaysia, 30450

Contact: Philip Rajan Devesahayam, MMed FRCS

Principal Investigator: Philip Rajan Devesahayam, MMed FRCS

Sub-Investigator: Hong Bee Ker, MD MRCP

Hospital Tuanku Fauziah; Recruiting

Kangar, Perlis, Malaysia, 01000

Contact: Mohd Zambri Ibrahim, MD MMed

Principal Investigator: Mohd Zambri Ibrahim, MD MMed

Sub-Investigator: Suhaila Abd Wahab, MBBS MMed

Hospital Queen Elizabeth; Recruiting

Kota Kinabalu, Sabah, Malaysia, 88200

Contact: Halimuddin Sawali, MBBS MS

Principal Investigator: Halimuddin Sawali, MBBS MS

Sub-Investigator: Heng Gee Lee, MBChB MRCP

Sarawak General Hospital; Recruiting

Kuching, Sarawak, Malaysia, 93586

Contact: Chun Yiing Wong, MBBS MMed

Principal Investigator: Chun Yiing Wong, MBBS MMed

Sub-Investigator: Hock Hin Chua, MD MRCP

Hospital Sungai Buloh; Recruiting

Sungai Buloh, Selangor, Malaysia, 47000

Contact: Sobani Din, MD MS

Principal Investigator: Sobani Din, MD MS

Sub-Investigator: Carren Sui Lin Teh, MD MS

Sub-Investigator: Kuldip Kaur Prem Kaur, MBBS MPH

Sub-Investigator: Nor Arisah Misnan, MBBS MMed

Hospital Sultanah Nur Zahirah; Recruiting

Kuala Terengganu, Terengganu, Malaysia, 20400

Contact: Amran Mohamad, MD MS

Principal Investigator: Amran Mohamad, MD MS

Sub-Investigator: Mohd Noor Ismail, MD MRCP

Kuala Lumpur General Hospital; Recruiting

Kuala Lumpur, Malaysia, 50586

Contact: Elang Kumaran Krishnan, MBBS MS

Principal Investigator: Elang Kumaran Krishnan, MBBS MS

Sub-Investigator: Chee Loon Leong, MBBS MMed

Hospital Melaka; Recruiting

Melaka, Malaysia, 75400

Contact: Linda Pei Fang Lim, MD MS

Principal Investigator: Linda Pei Fang Lim, MD MS

Sub-Investigator: Nor Zaila Zaidan, MD MMed

Sponsors and Collaborators

Hospital Sultanah Bahiyah

Hospital Tuanku Fauziah, Kangar, Perlis

Penang Hospital, Malaysia

Hospital Raja Permaisuri Bainun

Hospital Sungai Buloh, Selangor

Kuala Lumpur General Hospital

Hospital Tuanku Jaafar, Seremban, Negeri Sembilan

Hospital Melaka, Melaka

Hospital Enche Besar Hajjah Khalsom, Kluang, Johor

Hospital Raja Perempuan Zainab II, Kota Bahru, Kelantan

Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu

Hospital Tengku Ampuan Afzan, Kuantan, Pahang

Sarawak General Hospital

Hospital Queen Elizabeth, Malaysia

Investigators

• Study Chair: Siti Sabzah Mohd Hashim, MD MS; Hospital Sultanah Bahiyah

More Information

Additional Information:

AAO-HNS: Anosmia, Hyposmia, and Dysgeusia Symptoms of Coronavirus Disease | American Academy of Otolaryngology-Head and Neck Surgery 

Publications:

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:

Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020 Jul 28;71(15):889-890. doi: 10.1093/cid/ciaa330. No abstract available.

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127.

Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.

Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC 3rd. COVID-19 Anosmia Reporting Tool: Initial Findings. Otolaryngol Head Neck Surg. 2020 Jul;163(1):132-134. doi: 10.1177/0194599820922992. Epub 2020 Apr 28.

Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol. 2020 Jul;10(7):806-813. doi: 10.1002/alr.22579. Epub 2020 Jun 1.

Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, Boscolo-Rizzo P. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 May 26;323(20):2089-2090. doi: 10.1001/jama.2020.6771.

• Responsible Party: Siti Sabzah bt Mohd Hashim, MD, MS (ORL-HNS), Head of Otorhinolaryngology Service, Ministry of Health, Malaysia & Senior Consultant Otorhinolaryngologist, Hospital Sultanah Bahiyah
• ClinicalTrials.gov Identifier: NCT04384042
• Other Study ID Numbers: MCO-002; NMRR-20-934-54803 ( Other Identifier: National Medical Research Register (NMRR), Malaysia )
• First Posted: May 12, 2020
• Last Update Posted: February 25, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Siti Sabzah bt Mohd Hashim, MD, MS (ORL-HNS), Hospital Sultanah Bahiyah:

Cross-sectional study; Prevalence; Otorhinolaryngology; Infectious Diseases; Anosmia; Dysgeusia; Olfactory Disorders; Taste Disorders; COVID-19; SARS-CoV-2; Coronavirus 2019

Additional relevant MeSH terms:

Infections; COVID-19; Severe Acute Respiratory Syndrome; Anosmia; Dysgeusia; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Taste Disorders