Relationship Between Oral Findings and Salivary Factors in Sars-Cov-2 Patients

Evaluation of Oral Health Status and Cytokine Levels in Sars-Cov-2 Hospitalized Patients: A Randomized Clinical Trial

Two hundred individuals will be formed according to the study and control groups: Group-1: coronavirus 2 (Covid-19) (+) patients (n=100) and Group-2: Healthy individuals (in which the volunteers will be included due to group-1) (n=100). Oral examinations including DMFT scores, salivary flow rate, visible gingival index scores and radiographs (OPG) will be performed on both groups on the 1st appointment. Oral swap samples will be collected with sterile swap brushes (Six sample for each person) on the 1st, 7th and 30th days to evaluate the salivary immunoglobulins (Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM)) and cytokine (IL-1, IL-6, IL-10) levels. Blood samples will be collected to validate the oral swap test results.

Study Overview

• Status: Completed
• Conditions: COVID-19; Cytokine Storm; Missing Teeth; Decay, Dental
• Intervention / Treatment: Diagnostic test: ELISA test for Cytokines

Detailed Description

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the virus responsible for coronavirus disease 2019 (COVID-19) which also affects all systems of the body including the oral environment. Recent studies have demonstrated the association between oral health status and systemic diseases. including systemic infections and respiratory diseases. Aim of this study is to analyze the immunoglobulin and cytokine levels of SARS-CoV-2 patients and correlate the oral health status of these patients. Our hypotheses are, 1) Covid-19 affects individuals with low oral hygiene (high DMFT score) more severely, 2) Oral cytokine levels will increase similarly to blood levels in patients with Covid-19, 3) Oral immunoglobulin levels in patients with Covid-19 decreased similarly to those in blood. Oral examination of 100 Covid (+) patients which were hospitalized due to acute respiratory failure will be performed in the dental department of each faculty hospital. Decay-Missing-Filled Tooth (DMFT) scores, visible gingival plaque index (Löe-Silness), Bleeding on Probing (BoP) scores, and orthopantomographs (OPG) will be collected for each participant. Oral swap specimens will be collected (6 sample for each person) to evaluate the levels of salivary immunoglobulins (IgA, IgG, IgM) and cytokines (IL-1, IL-6, IL-10) on 1st, 7th, and 30th days. ELISA test will be performed for immunological analysis with ready-made kits (SunRed Biotech. Co, Shanghai, China). Full blood analyses will be performed to validate and correlate the actual cytokine and immunoglobulin levels.

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cem Peskersoy; Phone Number: +905326362659; Email: cem.peskersoy@ege.edu.tr
• Study Contact Backup: Name: Erdinc Kamer; Phone Number: +905323525261; Email: erdinc.kamer@gmail.com

Study Locations

• Turkey
  • Ankara, Turkey, 06500
    • Gazi University
  • Izmir, Turkey, 35100
    • Ege University
  • Izmir, Turkey, 35400
    • Izmir Katip Celebi University
  • İzmir, Turkey, 35600
    • Dokuz Eylul University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Covid (+) patients,
• Patients who were hospitalized due to Acute Respiratory Deficiency,
• Conscious patients in ICU (intensive care unit) or IDMC (Infectious Diseases and Microbiology Clinic).

Exclusion Criteria:

• Patients with Cancer,
• Patients with Autoimmune System diseases,
• Pregnant women,
• Patients with Immune Deficiency diseases (Acquired immune deficiency syndrome - AIDS, Autoimmune lymphoproliferative syndrome - ALPS , Chronic granulomatous disease - CGD, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Covid-19 (+) Patients; Oral Examination, Radiography, oral (salivary) swap sample collection will be performed.	Diagnostic test: ELISA test for Cytokines; ELISA tests specific for cytokines (IL-1, IL-6, IL-10) and immunoglobulins (IgA, IgG, IgM) will be performed by a biochemistry lab, both for blood samples and oral swap samples.
Active Comparator: Healthy Individuals; Oral Examination, Radiography, oral (salivary) swap sample collection will be performed.	Diagnostic test: ELISA test for Cytokines; ELISA tests specific for cytokines (IL-1, IL-6, IL-10) and immunoglobulins (IgA, IgG, IgM) will be performed by a biochemistry lab, both for blood samples and oral swap samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DMF Index	Decay, Missing, Filled teeth scores will be recorded and evaluated for both study groups.	Baseline (1st appointment)
Dental Plaque Status - GI	Gingival Index scores (visible dental plaque) will be evaluated for both study groups.	Baseline (1st appointment), 7th day (2nd appointment), 30th day (3rd appointment)
Periodontal Bleeding Status - BoP	Bleeding volume (ml/sec) on probing will be evaluated for both study groups.	Baseline (1st appointment), 7th day (2nd appointment), 30th day (3rd appointment)
Salivary Flow Rate	Salivary flow rate of each participant is calculated by measuring the unstimulated saliva volume (ml/min).	Baseline (1st appointment), 7th day (2nd appointment), 30th day (3rd appointment)
Oral Cytokine Levels	Oral cytokine levels will be evaluated for both study groups three times, due to the half-life of specific markers (IL-1, IL-6, IL-10).	Baseline (1st appointment), 7th day (2nd appointment), 30th day (3rd appointment)
Oral Immunoglobulin Levels	and immunoglobulin levels will be evaluated for both study groups three times, due to the half-life of specific markers (IgA, IgG, IgM).	Baseline (1st appointment), 7th day (2nd appointment), 30th day (3rd appointment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age Range of the Participants	The age distributions of the participants in the study will be recorded, so that it will be examined which age group is affected the most from Covid-19 disease (min age: 18, max age 80).	Baseline (1st appointment)
Gender Distribution	The gender distributions of the participants in the study will be recorded, so that it will be examined which gender group is affected the most from Covid-19 disease.	Baseline (1st appointment)
Systemical Diseases	The systemic diseases of the participants in the study will be recorded so that it will be examined with which systemic disease the Covid-19 disease can be most associated.	Baseline (1st appointment)

Collaborators and Investigators

• Sponsor: Ege University
• Collaborators: Gazi University; Izmir Katip Celebi University; Dokuz Eylul University; Istanbul Saglik Bilimleri University
• Investigators: Principal Investigator: Cem Peskersoy, Ege University Faculty of Dentistry

Publications and helpful links

General Publications

• Peskersoy C, Oguzhan A, Gurlek O. The Effect of Flowable Composite Resins on Periodontal Health, Cytokine Levels, and Immunoglobulins. Biomed Res Int. 2022 Apr 23;2022:6476597. doi: 10.1155/2022/6476597. eCollection 2022.
• Peskersoy C, Peker S, Kaya A, Unalp A, Gokay N. Evaluation of the relationship between migraine disorder andoral comorbidities: multicenter randomized clinical trial. Turk J Med Sci. 2016 Apr 19;46(3):712-8. doi: 10.3906/sag-1412-71.
• Alfaifi A, Sultan AS, Montelongo-Jauregui D, Meiller TF, Jabra-Rizk MA. Long-Term Post-COVID-19 Associated Oral Inflammatory Sequelae. Front Cell Infect Microbiol. 2022 Mar 2;12:831744. doi: 10.3389/fcimb.2022.831744. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): August 10, 2023

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Congenital Abnormalities; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Shock; Tooth Demineralization; Tooth Diseases; Stomatognathic System Abnormalities; Tooth Abnormalities; Dental Caries; Tooth Loss; Cytokine Release Syndrome; Anodontia
• Other Study ID Numbers: 21-6.1T/70

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