Malaysian COVID-19 Anosmia Study (Phase 1) - A Nationwide Multicentre Cross-Sectional Study

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

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 cross-sectional study is described here (the case-control study is described in a separate ClinicalTrials.gov record).

Study Overview

• Status: Completed
• Conditions: COVID-19; Anosmia; SARS-CoV Infection; Dysgeusia
• Intervention / Treatment: 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-19 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.

The aim of this cross-sectional study is to study the prevalence and characteristics of olfactory and taste disturbance in patients with COVID-19 infection in Malaysia. COVID-19 positive patients will be recruited from participating Malaysian Ministry of Health-designated COVID-19 treating hospitals across the country. Participants will answer an online questionnaire to evaluate and characterise these symptoms.

• Study Type: Observational
• Enrollment (Actual): 498

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Kuala Lumpur General Hospital
  • Melaka, Malaysia, 75400
    • Hospital Melaka
  • Johor
    • Kluang, Johor, Malaysia, 86000
      • Hospital Enche' Besar Hajjah Khalsom
  • Kedah
    • Alor Setar, Kedah, Malaysia, 05400
      • Hospital Sultanah Bahiyah
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15200
      • Hospital Raja Perempuan Zainab II
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Hospital TuanKu Jaafar
  • Pahang
    • Kuantan, Pahang, Malaysia, 25100
      • Hospital Tengku Ampuan Afzan
  • Penang
    • George Town, Penang, Malaysia, 10990
      • Penang Hospital
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun
  • Perlis
    • Kangar, Perlis, Malaysia, 01000
      • Hospital Tuanku Fauziah
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88200
      • Hospital Queen Elizabeth
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
  • Selangor
    • Sungai Buloh, Selangor, Malaysia, 47000
      • Hospital Sungai Buloh
  • Terengganu
    • Kuala Terengganu, Terengganu, Malaysia, 20400
      • Hospital Sultanah Nur Zahirah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population are 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.

These patients comprise those who either currently inpatient or already discharged into the community. For patients already discharged into the community, they will be invited to participate by phone call from the hospital treating team. Once verbal consent has been obtained, they a QR code or internet URL link to the online questionnaire website will be sent to these patients.

Description

Inclusion Criteria:

1. Age at least 18 years old
2. 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. Patients without a laboratory-confirmed COVID-19 diagnosis
3. Patients in intensive care unit at the time of study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Malaysian COVID-19 Cohort; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of olfactory and taste disturbances in COVID-19 patients	In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances	Within 2 weeks preceding the diagnosis of COVID-19 infection
Prevalence of olfactory disturbances in COVID-19 patients	Percentage of COVID-19 patients experiencing olfactory disturbances (anosmia or hyposmia)	Within 2 weeks preceding the diagnosis of COVID-19 infection
Prevalence of taste disturbances in COVID-19 patients	Percentage of COVID-19 patients experiencing taste disturbances	Within 2 weeks preceding the 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 (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)	Within 2 weeks preceding the 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.)	Prior to diagnosis of COVID-19 infection
Rating of baseline sense of smell & taste in COVID-19 patients prior to diagnosis of their infection	In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste before their diagnosis of COVID-19 infection	Prior to 2 weeks preceding the diagnosis of COVID-19 infection (Baseline)
Rating of sense of smell & taste in COVID-19 patients at time of diagnosis of their infection	In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of diagnosis of COVID-19 infection	Within 2 weeks preceding the diagnosis of COVID-19 infection
Rating of sense of smell & taste in COVID-19 patients at time of answering questionnaire survey	In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of answering questionnaire survey	Up to 6 months

Collaborators and Investigators

• Sponsor: Hospital Sultanah Bahiyah
• Collaborators: Sarawak General Hospital; Penang Hospital, Malaysia; Hospital Queen Elizabeth, Malaysia; Kuala Lumpur General Hospital; Hospital Raja Permaisuri Bainun; Hospital Tuanku Fauziah, Kangar, Perlis; Hospital Sungai Buloh, Selangor; 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
• Investigators: Study Chair: Siti Sabzah Mohd Hashim, MD MS, Hospital Sultanah Bahiyah

Publications and helpful links

General 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;:
• 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.
• 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.
• Lee SH, Yeoh ZX, Sachlin IS, Gazali N, Soelar SA, Foo CY, Low LL, Syed Alwi SB, Tengku Kamalden TMI, Shanmuganathan J, Zaid M, Wong CY, Chua HH, Yusuf S, Muhamad D, Devesahayam PR, Ker HB, Salahuddin Z, Mustafa M, Sawali H, Lee HG, Din S, Misnan NA, Mohamad A, Ismail MN, Periasamy C, Chow TS, Krishnan EK, Leong CL, Lim LPF, Zaidan NZ, Ibrahim MZ, Abd Wahab S, Mohd Hashim SS; Malaysian COVID-19 Anosmia Research Group. Self-reported symptom study of COVID-19 chemosensory dysfunction in Malaysia. Sci Rep. 2022 Feb 8;12(1):2111. doi: 10.1038/s41598-022-06029-6.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2020
• Primary Completion (ACTUAL): November 30, 2020
• Study Completion (ACTUAL): November 30, 2020

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (ACTUAL): May 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Prevalence; COVID-19; Infectious Diseases; Otorhinolaryngology; Cross-sectional study; Anosmia; Coronavirus 2019; Dysgeusia; Olfactory Disorders; Taste Disorders
• Additional Relevant MeSH Terms: Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Sensation Disorders; Olfaction Disorders; Taste Disorders; Severe Acute Respiratory Syndrome; COVID-19; Infections; Dysgeusia; Anosmia
• Other Study ID Numbers: MCO-001; NMRR-20-934-54803 (OTHER: National Medical Research Register (NMRR), Malaysia)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No