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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Procedure: nasopharyngeal and throat swab
* Procedure: collection of mucosal lining fluid
* Procedure: blood collection via fingerprick


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Index case and household contacts<br>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<br>* diagnostic specimens via nasopharyngeal swab and throat swab were collected following the current standard operating procedures.<br>Procedure: collection of mucosal lining fluid<br>* 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.<br>Procedure: blood collection via fingerprick<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, household contacts, mucosal immunitiy, antibodies