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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04384042
• Other study ID #: MCO-002
• Secondary ID: NMRR-20-934-5480
• Status: Recruiting
• Start date: June 6, 2020
• Est. completion date: March 31, 2021

Study information

• Verified date: February 2021
• Source: Hospital Sultanah Bahiyah
• Contact: Siti Sabzah Mohd Hashim, MD MS
• Phone: +604 740 7335
• Email: dr_ctsabzah[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anosmia
• Coronavirus Infections
• COVID-19
• Dysgeusia
• Infection
• Olfaction Disorders
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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.

Locations

Country	Name	City	State
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Penang Hospital	George Town	Penang
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Tuanku Fauziah	Kangar	Perlis
Malaysia	Hospital Enche' Besar Hajjah Khalsom	Kluang	Johor
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu	Sabah
Malaysia	Kuala Lumpur General Hospital	Kuala Lumpur
Malaysia	Hospital Sultanah Nur Zahirah	Kuala Terengganu	Terengganu
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Malaysia	Sarawak General Hospital	Kuching	Sarawak
Malaysia	Hospital Melaka	Melaka
Malaysia	Hospital Tuanku Jaafar	Seremban	Negeri Sembilan
Malaysia	Hospital Sungai Buloh	Sungai Buloh	Selangor

Sponsors (14)

Lead Sponsor

Collaborator

Hospital Sultanah Bahiyah

Hospital Enche Besar Hajjah Khalsom, Kluang, Johor, Hospital Melaka, Melaka, Hospital Queen Elizabeth, Malaysia, Hospital Raja Perempuan Zainab II, Kota Bahru, Kelantan, Hospital Raja Permaisuri Bainun, Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Hospital Sungai Buloh, Selangor, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Hospital Tuanku Fauziah, Kangar, Perlis, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Kuala Lumpur General Hospital, Penang Hospital, Malaysia, Sarawak General Hospital

Country where clinical trial is conducted

Malaysia, 

References & Publications (7)

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. — View Citation

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;:. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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