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

Recruiting

• Conditions: COVID-19; Periodontal Diseases; Oral Disease; Microbial Colonization; Innate Inflammatory Response; Mucosal Infection
• Interventions: Biological: COVID infection; Diagnostic Test: Oral examination; Biological: COVID vaccination

• Registration Number: NCT05212766
• Lead Sponsor: King's College London

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-01-24
• Study First Submitted QC: 2022-01-26
• Study First Posted: 2022-01-28
• Study Start: 2022-04-07
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-05
• Last Update Posted: 2023-10-10
• Primary Completion: 2023-10-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 750

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Vaccinated or unvaccinated uninfected South Asian ethnicity	Oral examination	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.
Asymptomatic / mild infected South Asian ethnicity	Oral examination	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
Symptomatic infected South Asian ethnicity	COVID vaccination	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.
Vaccinated or unvaccinated uninfected Caucasian ethnicity	COVID vaccination	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.
Vaccinated or unvaccinated uninfected Caucasian ethnicity	Oral examination	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.
Infected recovered Caucasian ethnicity	COVID infection	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of Caucasian ethnicity
Infected recovered Caucasian ethnicity	COVID vaccination	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of Caucasian ethnicity
Infected recovered South Asian ethnicity	COVID vaccination	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of South Asian ethnicity.
Symptomatic infected South Asian ethnicity	Oral examination	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.
Infected recovered South Asian ethnicity	Oral examination	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of South Asian ethnicity.
Symptomatic infected Caucasian ethnicity	Oral examination	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.
Vaccinated or unvaccinated uninfected South Asian ethnicity	COVID vaccination	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.
Asymptomatic / mild infected South Asian ethnicity	COVID infection	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
Asymptomatic / mild infected Caucasian ethnicity	COVID infection	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
Asymptomatic / mild infected Caucasian ethnicity	COVID vaccination	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
Symptomatic infected Caucasian ethnicity	COVID infection	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.
Infected recovered Caucasian ethnicity	Oral examination	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of Caucasian ethnicity
Asymptomatic / mild infected South Asian ethnicity	COVID vaccination	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
Symptomatic infected South Asian ethnicity	COVID infection	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.
Infected recovered South Asian ethnicity	COVID infection	Participants will have experienced moderate or severe symptomatic infection (positive test, admission) and recovered. They will identify as of South Asian ethnicity.
Symptomatic infected Caucasian ethnicity	COVID vaccination	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.
Vaccinated or unvaccinated uninfected Caucasian ethnicity	COVID infection	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.
Asymptomatic / mild infected Caucasian ethnicity	Oral examination	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

Primary Outcome Measures

Name	Time	Method
Relationship between oral mucosal immunity and microbiome on COVID outcomes in different ethnic groups	16 weeks	Multiple assessments

Secondary Outcome Measures

Name	Time	Method
Impact of pre-existing oral disease	16 weeks	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
Impact of immunity and oral microbiome	16 weeks	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

Trial Locations

Locations (1)

Guy's and St Thomas' NHS Trust / King's College London; 🇬🇧 London, United Kingdom