Mucosal Immunity Against SARS-CoV-2 Infection in COVID-19 Patients (MuCo)

Mucosal Immunity in Patients Diagnosed With SARS-CoV-2 Infection and Their Household Contacts

In this study nasal fluid (mucosal lining fluid), nose and throat swabs and blood was collected from patients with a confirmed SARS-CoV-2 infection who remained in home isolation, as well as from their household contacts who remained in home quarantine. On the collected nose and throat swabs a coronavirus PCR was performed. Antibodies against SARS-CoV-2 were measured in the mucosal lining fluid and blood samples.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Procedure: nasopharyngeal and throat swab; Procedure: collection of mucosal lining fluid; Procedure: blood collection via fingerprick

Detailed Description

Objective:

Primary Objective: to analyse the development of mucosal immunity against SARS-CoV-2 in nasal fluid of Covid-19 patients and their household contacts

Secondary Objective(s):

• To descriptively analyse the correlation of mucosal antibodies with viral diagnostics and disease symptoms
• To determine the correlation between mucosal and serum antibody levels
• To study the functionality of serum and mucosal antibodies

Study design: A single-site, observational, prospective cohort study among COVID-19 patients and their household contacts Study population: The study will be conducted among COVID-19 patients with a laboratory-confirmed infection with SARS-CoV-2, as well as household contacts remaining in home quarantine at the same address, among secondary and tertiary hospital careworkers in the provinces of Gelderland and Noord-Brabant in The Netherlands.

Intervention (if applicable): N/A

Main study parameters/endpoints:

Mucosal antibodies: descriptive analysis of SARS-CoV-2 IgG, IgA, IgM and IgD concentrations in nasal fluid at the various collection moments.

Viral diagnostics: presence of SARS-CoV-2 in diagnostic specimens collected at inclusion visit.

Disease symptoms: presence of respiratory complaints in participants. Serum antibodies: descriptive analysis of SARS-CoV-antibody concentrations in serum at day 28 Antibody functionality: descriptive analysis of antibody functionality of serum and nasal fluid samples, including virus neutralization

• Study Type: Observational
• Enrollment (Actual): 187

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

laboratory confirmed Sars-Cov-2 cases and their household contacts.

Description

Inclusion Criteria:

• Index case:

  • Laboratory-confirmed case of SARS-CoV-2, with a positive indication for home isolation, and;
  • With at least 2 household contacts remaining in home quarantine at the same address
• Household contacts For each index case, the study will seek to recruit as many household contacts as possible in the same house as the index case. All household contacts of the index case remaining in home quarantine in the same house as the index case will be asked to participate.

Exclusion Criteria:

• Covid-19 patients with a negative indication for home isolation, or having less than 2 household contacts remaining in home quarantine at the same address. For fingerprick blood collection, participants who have a medical indication against fingerprick blood collection will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Index case and household contacts; nasophryngeal and throat swab at day 0.; collection of mucosal lining fluid: day 0, 7, 14, 28 for index case and day 0, 3, 6, 28 for household contacts.; fingerprick at day 28 (optional).; daily record of symptoms from day 0-28.

Procedure: nasopharyngeal and throat swab; diagnostic specimens via nasopharyngeal swab and throat swab were collected following the current standard operating procedures.; Procedure: collection of mucosal lining fluid; MLF will be collected via nasal absorption at the inclusion visit by study staff and four more time points by the parents or by the children themselves. Nasal absorption is performed by maneuvering a strip of synthetic absorptive matrices (SAM) into the lumen of the nostril, avoiding rubbing against the nasal mucosa. The outside of the nose is then pressed with a finger to cause apposition of the SAM against the mucosa.; Procedure: blood collection via fingerprick; Participants will be asked to wash their hands with soap and warm water. The procedure involves cleaning the ball of the fingertip with an alcohol swab, then using a sterile disposable lancet to pierce the skin (BD Microtainer Lancet or similar). The lancet is placed in a spring-loaded device, which propels the lancet a fixed distance (a few mm) into the skin when the trigger is pressed. Approximately 10-20 drops of blood (0.3 ml) will then be collected with a sterile capillary tube. The participant is given a cotton wool pad to mop up any extra blood, and an elastoplast-type bandage is placed over the finger if necessary. Fingerprick blood samples will only be collected from participants older than 6 months at 28-32 days after the first home visit (d0). Lancet length will be adjusted for age (2.0 mm for participants 8 years and older, 1.5 mm for participants older than 6 months and younger than 8 years).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucosal antibodies	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 0
Mucosal antibodies	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 3 (index cases)
Mucosal antibodies	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 6 (index cases)
Mucosal antibodies	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 7 (household contacts)
Mucosal antibodies	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 14 (household contacts)
Mucosal antibodies in all participants	Descriptive analysis of SARS-CoV-2 IgG, IgM and IgA concentrations in nasal fluid	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 infection	SARS-CoV-2 PCR on nasopharyngeal swab and throat swab	day 0
Serum antibodies	Descriptive analysis of SARS-CoV-2 antibody concentrations in serum at day 28.	day 28
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 0
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 3 (index cases)
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 6 (index cases)
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 7 (household contacts)
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 14 (household contacts)
Functional antibody assays	Descriptive analysis of the functionality of SARS-CoV-2 mucosal and serum antibodies	Day 28

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Dimitri Diavatopoulos, Dr, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2020
• Primary Completion (Actual): May 13, 2020
• Study Completion (Actual): May 13, 2020

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; antibodies; household contacts; mucosal immunitiy
• 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; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: 2020-6342; NL73418.091.20 (Registry Identifier: CCMO)

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