Role of the Oral Microbiome & Mucosal Immunity in COVID-19 Disease (MIMSA)

Role of the Oral Microbiome & Mucosal Immunity in COVID-19 Disease: Diagnostic/Prognostic Utility in South Asian Populations

Determining whether in the mouth there are differences between the participant groups in the nature and activity of mucosal innate immunity, in immune responses to SARS-COV2 antigens, or in the oral microbiome

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Periodontal Diseases; Microbial Colonization; Oral Disease; Mucosal Infection; Innate Inflammatory Response
• Intervention / Treatment: Biological: COVID vaccination; Diagnostic test: Oral examination; Biological: COVID infection

Detailed Description

Cross sectional with longitudinal component

• Stimulated whole mouth fluid (SWMF) and blood samples from South Asian and non-Asian populations
• Controls, and COVID-19 patients in both populations.
• Oral disease questionnaire and clinical examination
• Separation of SWMF into pellet for DNA extraction for microbiomics and supernatant for cell phenotype analysis, cytokines and antibodies to SARS-CoV2 antigens

• Study Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

• Study Contact: Name: Stephen J Challacombe, PhD; Phone Number: 02971887188; Email: stephen.challacombe@kcl.ac.uk
• Study Contact Backup: Name: Mark Ide, PhD; Phone Number: 01711887188; Email: mark.ide@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and St Thomas' NHS Trust / King's College London
    • Contact: Mark Ide, PhD; Email: mark.ide@kcl.ac.uk

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants, both South Asian and White British will be recruited by advertisement within KCL or social media, from non-COVID in-patients or outpatients or attending A&E at GSTT and at SARS-CoV2 antigen testing centres and vaccination centres and at PIC sites. Also patients either seen at GSTT or admitted as in-patients to GSTT or KCH and found to be SARS-CoV2 positive. Patients who have had COVID may be invited directly to participate by advertising at sites specified above or be attending either the post-COVID or ICU follow-up outpatient clinics

Description

Inclusion Criteria:

• • South Asian and White British persons and those diagnosed with symptomatic or asymptomatic COVID-19 infection.

  • Aged 18 or over. Able to understand and consent.
  • Uninfected subjects: no history of COVID-19; not vaccinated; (negative for anti-SARS-CoV2 nucleoprotein antibodies at lab)
  • For patient groups: Confirmed COVID-19 positivity, symptoms and symptom onset within the past 21 days; Be recently hospitalised with COVID-19 disease; Have COVID-19 disease proven by PCR testing for SARS-CoV-2 within the last 21 days; COVID disease severity graded as per NIH/WHO.
  • Recovered groups: Have had COVID-19 disease proven by PCR testing for SARS-CoV-2. COVID disease severity graded as per WHO or NIH equivalent criteria
  • Those willing to participate on a single occasion but unwilling to participate with longitudinal samples will not be excluded.
  • Smoking, obesity, diabetes, heart disease, antibiotics or treatment related to COVID is not excluded.

Exclusion Criteria:

• • Those patients unwilling to participate, those unable to understand sufficiently to give informed consent and those unable to participate due to the severity of COVID-19 disease. Those patients classified as not either South Asian or White British heritage.

  • Patients with malignancy, pregnancy, long term immune suppression, inability to give informed consent, not willing or able to have oral examination.
  • Diabetes not excluded but screening for diabetes will be performed: glucose will be assessed in blood/serum sample (150ul).

Exclusion criteria summary:

• Critically ill participants who cannot give informed consent
• Those who are not willing to have an oral examination, or donate blood or saliva samples.
• Those who cannot chew / drool to provide a SWMF sample due to severe/critical medical conditions
• Participants with known malignancies or who are pregnant
• Participants who are on long-term immunosuppressants (e.g. for autoimmune diseases)
• Participation in other current research that is designed to, or is expected to alter the immune response.
• Inability to communicate, understand or read English.

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vaccinated or unvaccinated uninfected South Asian ethnicity; Participants will have not experienced infection (positive test) - we will aim to recruit both vaccinated and unvaccinated individuals although the latter may be harder to recruit. They will identify as of South Asian ethnicity. Uninfected subjects, will be recruited by advertisement within KCL or social media, from non-COVID in-patients or outpatients or attending A&E at GSTT and at SARS-CoV2 antigen testing centres and vaccination centres and at PIC sites.	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status
Asymptomatic / mild infected South Asian ethnicity; Participants will have experienced asymptomatic or mild infection (positive test). They will identify as of South Asian ethnicity. Volunteers or subjects attending SARS-CoV2 testing centres who are found to be antigen positive or In-patients who have positive Covid tests and designated as asymptomatic/mild but admitted for non-covid reasons or those attending A&E with COVID but designated as mild/asymptomatic	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Symptomatic infected South Asian ethnicity; Participants will have experienced moderate or severe symptomatic infection (positive test, admission). They will identify as of South Asian ethnicity. Patients either seen at GSTT or admitted as in-patients to GSTT or KCH and found to be SARS-CoV2 positive by RT-PCR in nasopharyngeal samples and designated as moderate/severe on the NIH/NIMR COVID severity scale.	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Infected recovered South Asian ethnicity; Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of South Asian ethnicity.	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Vaccinated or unvaccinated uninfected Caucasian ethnicity; Participants will have not experienced infection (positive test) - we will aim to recruit both vaccinated and unvaccinated individuals although the latter may be harder to recruit. They will identify as of Caucasian ethnicity. Uninfected subjects, will be recruited by advertisement within KCL or social media, from non-COVID in-patients or outpatients or attending A&E at GSTT and at SARS-CoV2 antigen testing centres and vaccination centres and at PIC sites.	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Asymptomatic / mild infected Caucasian ethnicity; Participants will have experienced asymptomatic or mild infection (positive test). They will identify as of Caucasian ethnicity. Volunteers or subjects attending SARS-CoV2 testing centres who are found to be antigen positive or In-patients who have positive Covid tests and designated as asymptomatic/mild but admitted for non-covid reasons or those attending A&E with COVID but designated as mild/asymptomatic	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Symptomatic infected Caucasian ethnicity; Participants will have experienced moderate or severe symptomatic infection (positive test, admission). They will identify as of Caucasian ethnicity. Patients either seen at GSTT or admitted as in-patients to GSTT or KCH and found to be SARS-CoV2 positive by RT-PCR in nasopharyngeal samples and designated as moderate/severe on the NIH/NIMR COVID severity scale.	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19
Infected recovered Caucasian ethnicity; Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of Caucasian ethnicity	Biological: COVID vaccination; Vaccination against COVID 19; Diagnostic test: Oral examination; Assessment of oral and periodontal health status; Biological: COVID infection; Infections with COVID 19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between oral mucosal immunity and microbiome on COVID outcomes in different ethnic groups	Multiple assessments	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of immunity and oral microbiome	To determine whether the presence of pre-existing oral disease is related to susceptibility to SARS-CoV2 infection, to severity of COVID-19 disease or relates to the nature of mucosal immunity and to the composition and activity of the oral microbiome	16 weeks
Impact of pre-existing oral disease	To determine whether the presence of pre-existing oral disease is related to susceptibility to SARS-CoV2 infection, to severity of COVID-19 disease or relates to the nature of mucosal immunity and to the composition and activity of the oral microbiome	16 weeks

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Guy's and St Thomas' NHS Foundation Trust; UK Research and Innovation
• Investigators: Principal Investigator: Stephen J Challacombe, PhD, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Estimated): October 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; periodontal disease; oral health; mucosal immunity
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Stomatognathic Diseases; COVID-19; Inflammation; Infections; Communicable Diseases; Mouth Diseases; Periodontal Diseases
• Other Study ID Numbers: MIMSA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is likely that anonymised data may be shared with colleagues carrying out a linked study in India, although the exact nature of this yet to be confirmed

Drug and device information, study documents

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