Oral and Olfactory Complications of Recovered COVID-19 Patients

Oral and Olfactory Complications of Recovered COVID-19 Patients: A Prospective Cohort Study

This cohort study aims to investigate the long-standing chemosensory disorders and oral manifestation after recovery of the COVID-19 illness. A correlation between the long-standing symptoms and the COVID-19 severity grade will be very important to understand and clarify the aetiology of these symptoms.

Study Overview

• Status: Recruiting
• Conditions: Dysgeusia; Olfactory Disorder; Oral Complication
• Intervention / Treatment: Diagnostic test: Gustatory and olfactory function test; Diagnostic test: Molecular assessment of saliva

Detailed Description

This prospective cohort study aims to investigate the long-standing chemosensory disorders and oral manifestation after recovery of the COVID-19 illness. A correlation between the long-standing symptoms and the COVID-19 severity grade will be very important to understand and clarify the aetiology of these symptoms.

Study objectives:

1. To describe the frequency and severity of oral signs and chemosensory disorders that persist after the recovery of COVID-19 and to examine whether "taste disorders" can be discriminated into an- or hypogeusia and an- or hyposmia.
2. To report any correlation between the severity grade of COVID-19 and the resulting standing symptoms.
3. To describe the oral microbiome after infection with COVID-19 and to describe possible changes in comparison to normal healthy individuals.

Clinical and -if indicated- radiological examination to assess the long-term oral and chemosensory impairment and complaints of COVID-19 patients after their recovery shall be performed in an interdisciplinary setting of Maxillofacial Surgery, ENT and Medical Microbiology.

The study subjects will be divided into three groups according to the severity grade of illness: non-hospitalized, hospitalized, and intensive care patients. All adult COVID-19 recovery patients (exceeding the age of 18) will be included in the study. The time between illness and study recruitment shall be at least 3 months. Exclusion criteria are psychiatric or neurological diseases, previous trauma, surgery or radiotherapy in the oral or nasal cavities, pre-existing taste or smell dysfunctions or chronic rhinosinusitis.

The study variables include age, sex, co-morbidities, possible causes of exclusion from the study. The oral health assessment will be performed by examination of: periodontal status, assessment of oral lesions, a radiological examination by using panoramic x-ray if clinically indicated, photo documentation, objective evaluation of the olfactory and gustatory functions with psychophysical tests. The gustatory and olfactory function will be tested by using the combined Burghart Screening 12 test containing smelling sticks and taste strips (Fa. MediSense, Groningen, Netherlands). Evaluation of taste and smell is performed by offering the sticks/strips and demand a forced multiple choice.

• Study Type: Observational
• Enrollment (Estimated): 402

Contacts and Locations

• Study Contact: Name: Sameh Attia, MSc; Phone Number: 00496419946110; Email: Sameh.Attia@dentist.med.uni-giessen.de

Study Locations

• Germany
  • Hesse
    • Gießen, Hesse, Germany, 35392
      • Recruiting
      • Justus-Liebig University
      • Contact: Sameh Attia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Study subjects will be divided into three groups according to the severity grade of illness: non-hospitalized, hospitalized, and intensive care patients.

Description

Inclusion Criteria:

• All adult COVID-19 recovery patients (exceeding the age of 18) will be included in the study. The time between illness and study recruitment shall be at least 3 months.

Exclusion Criteria:

• Exclusion criteria are psychiatric or neurological diseases, previous trauma, surgery or radiotherapy in the oral or nasal cavities, pre-existing taste or smell dysfunctions or chronic rhinosinusitis.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mild Illness; Recovered COVID-19 patients who experienced a mild clinical course	Diagnostic test: Gustatory and olfactory function test; The gustatory and olfactory function will be tested by using the combined Burghart Screening 12 test containing smelling sticks and taste strips (Fa. MediSense, Groningen, Netherlands). Evaluation of taste and smell is performed by offering the sticks/strips and demand a forced multiple choice.; Diagnostic test: Molecular assessment of saliva; Saliva samples will be taken for molecular biological determination of the oral microbiome. The microbiome is determined at the Institute for Medical Microbiology by 16s-rRNA gene analysis with Next Generation Sequencing and bioinformatics.
Moderate Illness; Recovered COVID-19 patients who experienced a moderate clinical course	Diagnostic test: Gustatory and olfactory function test; The gustatory and olfactory function will be tested by using the combined Burghart Screening 12 test containing smelling sticks and taste strips (Fa. MediSense, Groningen, Netherlands). Evaluation of taste and smell is performed by offering the sticks/strips and demand a forced multiple choice.; Diagnostic test: Molecular assessment of saliva; Saliva samples will be taken for molecular biological determination of the oral microbiome. The microbiome is determined at the Institute for Medical Microbiology by 16s-rRNA gene analysis with Next Generation Sequencing and bioinformatics.
Severe Illness; Recovered COVID-19 patients who experienced a severe clinical course	Diagnostic test: Gustatory and olfactory function test; The gustatory and olfactory function will be tested by using the combined Burghart Screening 12 test containing smelling sticks and taste strips (Fa. MediSense, Groningen, Netherlands). Evaluation of taste and smell is performed by offering the sticks/strips and demand a forced multiple choice.; Diagnostic test: Molecular assessment of saliva; Saliva samples will be taken for molecular biological determination of the oral microbiome. The microbiome is determined at the Institute for Medical Microbiology by 16s-rRNA gene analysis with Next Generation Sequencing and bioinformatics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periodontal health	Community Periodontal Index (CPI) of the World Health Organization (WHO) will be used to assess periodontal health (continuous variable)	At least 3 months after recovery of COVID-19
Oral mucocutaneous lesions	An intraoral examination will be carried out to assess the presence of any mucocutaneous lesions (dichotomous variable)	At least 3 months after recovery of COVID-19
Gustatory function	Burghart Sniffin' Sticks "Screening 12 Test" will be used to assess gustatory function (continuous variable)	At least 3 months after recovery of COVID-19
Olfactory function	Burghart Sniffin' Sticks "Screening 12 Test" will be used to assess olfactory function (continuous variable)	At least 3 months after recovery of COVID-19

Collaborators and Investigators

• Sponsor: University of Giessen
• Collaborators: University of Kiel; Masaryk University

Publications and helpful links

General Publications

• Attia S, Howaldt HP. Impact of COVID-19 on the Dental Community: Part I before Vaccine (BV). J Clin Med. 2021 Jan 14;10(2):288. doi: 10.3390/jcm10020288.
• Bottger S, Zechel-Gran S, Streckbein P, Knitschke M, Hain T, Weigel M, Wilbrand JF, Domann E, Howaldt HP, Attia S. A New Type of Chronic Wound Infection after Wisdom Tooth Extraction: A Diagnostic Approach with 16S-rRNA Gene Analysis, Next-Generation Sequencing, and Bioinformatics. Pathogens. 2020 Sep 28;9(10):798. doi: 10.3390/pathogens9100798.
• Ammar N, Aly NM, Folayan MO, Mohebbi SZ, Attia S, Howaldt HP, Boettger S, Khader Y, Maharani DA, Rahardjo A, Khan I, Madi M, Shamala A, Al-Batayneh OB, Rashwan M, Pavlic V, Cicmil S, Galluccio G, Polimeni A, Mancino D, Arheiam A, Dama MA, Nyan M, Phantumvanit P, Kim JB, Choi YH, Castillo JL, Joury E, Abdelsalam MM, Alkeshan MM, Hussein I, Vukovic AP, Iandolo A, Kemoli AM, El Tantawi M. Knowledge of dental academics about the COVID-19 pandemic: a multi-country online survey. BMC Med Educ. 2020 Nov 2;20(1):399. doi: 10.1186/s12909-020-02308-w.
• Ammar N, Aly NM, Folayan MO, Khader Y, Virtanen JI, Al-Batayneh OB, Mohebbi SZ, Attia S, Howaldt HP, Boettger S, Maharani DA, Rahardjo A, Khan I, Madi M, Rashwan M, Pavlic V, Cicmil S, Choi YH, Joury E, Castillo JL, Noritake K, Shamala A, Galluccio G, Polimeni A, Phantumvanit P, Mancino D, Kim JB, Abdelsalam MM, Arheiam A, Dama MA, Nyan M, Hussein I, Alkeshan MM, Vukovic AP, Iandolo A, Kemoli AM, El Tantawi M. Behavior change due to COVID-19 among dental academics-The theory of planned behavior: Stresses, worries, training, and pandemic severity. PLoS One. 2020 Sep 29;15(9):e0239961. doi: 10.1371/journal.pone.0239961. eCollection 2020.

Helpful Links

• Impact of COVID-19 on The Dental Community

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): May 28, 2025

Study Registration Dates

• First Submitted: March 7, 2021
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Oral Manifestations; Olfactory Manifestations
• Additional Relevant MeSH Terms: Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Sensation Disorders; Taste Disorders; COVID-19; Dysgeusia
• Other Study ID Numbers: OORCV

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