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

• ClinicalTrials.gov Identifier: NCT04390165
• Recruitment Status: Completed
• First Posted: May 15, 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 cross-sectional study is described here (the case-control 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-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 Design

• Study Type: Observational
• Actual Enrollment: 498 participants
• Observational Model: Case-Only
• Time Perspective: Cross-Sectional
• Official Title: Olfactory and Gustatory Disturbances as a Clinical Presentation of Coronavirus Disease 2019 (COVID-19) Infection in Malaysia - A Nationwide Multicentre Cross-Sectional Study
• Actual Study Start Date: June 6, 2020
• Actual Primary Completion Date: November 30, 2020
• Actual Study Completion Date: November 30, 2020

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Presence or absence of olfactory and taste disturbances in COVID-19 patients [ Time Frame: Within 2 weeks preceding the 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. Prevalence of olfactory disturbances in COVID-19 patients [ Time Frame: Within 2 weeks preceding the diagnosis of COVID-19 infection ]
   Percentage of COVID-19 patients experiencing olfactory disturbances (anosmia or hyposmia)
3. Prevalence of taste disturbances in COVID-19 patients [ Time Frame: Within 2 weeks preceding the diagnosis of COVID-19 infection ]
   Percentage of COVID-19 patients experiencing taste disturbances

Secondary Outcome Measures :

1. Clinical manifestations of study participants [ Time Frame: Within 2 weeks preceding the 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 (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
2. Other pre-existing health conditions [ Time Frame: Prior to diagnosis of COVID-19 infection ]
   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. Rating of baseline sense of smell & taste in COVID-19 patients prior to diagnosis of their infection [ Time Frame: Prior to 2 weeks preceding the diagnosis of COVID-19 infection (Baseline) ]
   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
4. Rating of sense of smell & taste in COVID-19 patients at time of diagnosis of their infection [ Time Frame: Within 2 weeks preceding the diagnosis of COVID-19 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
5. Rating of sense of smell & taste in COVID-19 patients at time of answering questionnaire survey [ Time Frame: Up to 6 months ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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

Contacts and Locations

Locations

Malaysia

Hospital Enche' Besar Hajjah Khalsom

Kluang, Johor, Malaysia, 86000

Hospital Sultanah Bahiyah

Alor Setar, Kedah, Malaysia, 05400

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, Malaysia, 15200

Hospital Tuanku Jaafar

Seremban, Negeri Sembilan, Malaysia, 70300

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, Malaysia, 25100

Penang Hospital

George Town, Penang, Malaysia, 10990

Hospital Raja Permaisuri Bainun

Ipoh, Perak, Malaysia, 30450

Hospital Tuanku Fauziah

Kangar, Perlis, Malaysia, 01000

Hospital Queen Elizabeth

Kota Kinabalu, Sabah, Malaysia, 88200

Sarawak General Hospital

Kuching, Sarawak, Malaysia, 93586

Hospital Sungai Buloh

Sungai Buloh, Selangor, Malaysia, 47000

Hospital Sultanah Nur Zahirah

Kuala Terengganu, Terengganu, Malaysia, 20400

Kuala Lumpur General Hospital

Kuala Lumpur, Malaysia, 50586

Hospital Melaka

Melaka, Malaysia, 75400

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• 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: NCT04390165
• Other Study ID Numbers: MCO-001; NMRR-20-934-54803 ( Other Identifier: National Medical Research Register (NMRR), Malaysia )
• First Posted: May 15, 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