Comparative Analysis of Anti-COVID-19 (Severe Acute Respiratory Syndrome) Humoral and Memory T Cell Responses in Children With Various Degrees of Immunosuppression: (PEDIMMCO)

March 2, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Comparative Analysis of Anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome) Humoral and Memory T Cell Responses in Children With Various Degrees of Immunosuppression: a Case-control Study

Adaptive immune responses are essential for clearing viral infections and retention of virus specific memory populations is required for long-term immunity. However, there is still uncertainty about whether adaptive immune responses to SARS-CoV-2 are protective. Such knowledge is of immediate relevance, as it will provide insights into immunity of SARS-CoV-2 infection and thus help define future immunization strategies. Because of the importance of asymptomatic cases in children, a specific study is needed in this population in order to determine their individual and collective protective capacity. This is even truer for immune compromised children that likely have severe forms of the disease with active and prolonged viral replication in whom it is therefore essential to determine the extent of sero conversion but also the quality and duration of the memory responses.

For this purpose, we plan to analyze the anti-SARS-CoV-2 humoral and memory T cell responses, in different groups of immuno-compromized children (i.e with different levels/type of immunosuppression; HIV, renal or stem cell transplantation, anti-TNF or methotrexate treatment) and healthy controls seen in 3 University Hospitals, in order to determine the proportion of children with SARS-CoV-2 specific humoral responses, their protective capacity, the magnitude and the quality of the SARS-Cov-2 memory T cells but also their long term persistence at 1 year.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Adaptive immune responses are essential for clearing viral infections and retention of virus specific memory populations is required for long-term immunity. However, there is still uncertainty about whether adaptive immune responses to SARS-CoV-2 are protective. Such knowledge is of immediate relevance, as it will provide insights into immunity of SARS-CoV-2 infection and thus help define future immunization strategies. Because of the importance of asymptomatic cases in children, a specific study is needed in this population in order to determine their individual and collective protective capacity. This is even truer for immuno-compromised children that likely have severe forms of the disease with active and prolonged viral replication in whom it is therefore essential to determine the extent of seroconversion but also the quality and duration of the memory responses.

For this purpose, we plan to analyze the anti-SARS-CoV-2 humoral and memory T cell responses, in different groups of immuno-compromized children (i.e with different levels/type of immunosuppression; HIV, renal or stem cell transplantation, anti-TNF or methotrexate treatment) and healthy controls seen in 3 University Hospitals, in order to determine the proportion of children with SARS-CoV-2 specific humoral responses, their protective capacity, the magnitude and the quality of the SARS-Cov-2 memory T cells but also their long term persistence at 1 year.

In this study, we will evaluate the proportion of children who developed anti-SARS-CoV-2 humoral and cellular memory immune responses and the protective capacity of these responses in different groups of immune-compromised children.

As explained above, clinical significance of SARS-CoV-2 varies among different immune-compromised populations, in relation to the individual degree and type of immunosuppression. It is therefore necessary to obtain data on post infection protective immunity in different groups of immunosuppressed children. The intervention added for this study, blood samples will be taken. The blood sample will consist of two to three (depending on weight) additional tubes (heparin-lithium, dry) between 5 ml and 15 ml each taken during a blood test necessary for the patient's standard care. A second blood sample will be taken one year later for those with a positive response to SARS-CoV-2 and for vaccinated children. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of drugs in the pediatric population".

Study Type

Observational

Enrollment (Actual)

205

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75019
        • Hopital Robert Debre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 15 years (Child)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

In this study, we will evaluate the proportion of children who developed anti-SARS-CoV-2 humoral and cellular memory immune responses and the protective capacity of these responses in different groups of immune-compromised children.

As explained above, clinical significance of SARS-CoV-2 varies among different immune-compromised populations, in relation to the individual degree and type of immunosuppression. It is therefore necessary to obtain data on post infection protective immunity in different groups of immunosuppressed children.

To these purpose, the study will benefit from a Network of Pediatric Physicians used to work or collaborating together, with experience of children's studies and strong adherence to the study.

Description

Inclusion Criteria:

  • Children over 0 days and under 16 years of age seen in consultation for the follow-up of their pathology or immunosuppressive treatment (see above, Groups of patients).
  • Several cases groups will be considered in this study, presented with immunocompromised state or immunosuppressive treatment (i. e. children with: HIV infection, Hematologic Malignancy treated by conventional chemotherapy, Hematologic pathology treated by allogenic stem cell transplantation, inflammatory bowel disease treated by anti-TNF, idiopathic juvenile arthritis treated by methotrexate, treated by renal transplantation; see above, paragraph groups of patients for details).

Children over 0 days and under 16 years of age considered as control will be non-immunosuppressed children without chronic inflammation, attending consultation for preoperative assessment or congenital abnormalities of the kidney and urinary tract, for Nephropathies without renal impairment (eDFG > 45mL/min/1.73m), for non-inflammatory intestinal (polyposis, Chronic intestinal pseudo-obstruction, short bowel syndrome) or pancreatic (hereditary pancreatitis) pathologies.For comparisons, healthy children will be age-matched with each case.

  • Informed consent of the holder (s) of the exercise of parental authority
  • Affiliation to a social security scheme

Exclusion Criteria:

  • Children who have a signs of a current infection.
  • Use of immunoglobulins or blood products within 3 months prior to enrolment.
  • Children who received one or more doses of SARS-Cov-2 vaccine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
children with controlled HIV
Children over 0 days and under 16 years old, with controlled HIV
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.
children with hematologic Malignancy treated by conventional chemotherapy
Children over 0 days and under 16 years old, with Hematologic Malignancy treated by conventional chemotherapy
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.
Children with inflammatory bowel disease treated by anti-TNF at least 6 weeks
Children over 0 days and under 16 years old, with inflammatory bowel disease treated by anti-TNF
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.
Children with idiopathic juvenile arthritis
Children over 0 days and under 16 years old, with idiopathic juvenile arthritis treated by methotrexate:
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.
Children treated by renal transplantation
Children over 0 days and under 16 years old, treated by renal transplantation from more than 3 months:
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.
Children attending consultation

Children over 0 days and under 16 years old, without immunodepression or chronic inflammation attending consultation for :

  • preoperative assessment
  • -congenital abnormalities of the kidney and urinary tract:
  • Nephropathies without renal impairment (eDFG > 45mL/min/1.73m2)
  • Non-inflammatory intestinal (polyposis, Chronic intestinal pseudo-obstruction, short bowel syndrome) or pancreatic (hereditary pancreatitis) pathologies This group of children will be a control group (age matched healthy children, non-immunosuppressed).
Other: blood collection

Depending on the weight of the child, between 5ml and 15ml of blood will be collected during a blood test necessary for the conventional care of the patient. A second blood sample will be taken one year later. The volume of blood taken does not exceed the volume allowed by the guideline "Ethical considerations for clinical trials of medicinal products conducted in the paediatric population".

We will analyse:

  1. Specific antibody responses (IgM, IgG, and immunoglobulin A (IgA) anti SARS-Cov-2) by quantitative chemiluminescence analysis.
  2. Protective neutralizing capacity of these antibodies (neutralizing antibodies against SARS-cOV-2) by neutralization test.
  3. SARS-Cov-2 specific memory T cell responses by multiparametric flow cytometry in order to characterize their maturation, differentiation, senescence, activation, secretion of interleukin (cytokines 2) , IFN-g, TNF) or Interferon-gamma (IFN-g) ELISPOT assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numbers of subjects with positive IgM
Time Frame: at baseline
Numbers of subjects with positive IgM titer levels against SARS-Cov-2 (according to the manufacturer) at baseline.
at baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numbers of subjects with positive IgG
Time Frame: at baseline and at 12 months
Numbers of subjects with positive immunoglobulin G (IgG) SARS-Cov-2 (according to the manufacturer)
at baseline and at 12 months
Numbers of subjects with positive titers
Time Frame: at baseline and at 12 months
Number of subjects with positive titers
at baseline and at 12 months
Percentage of SARS-CoV-2 memory T
Time Frame: at baseline ans at 12 months
Percentage and counts of SARS-CoV-2 memory T cells in lymphocytes
at baseline ans at 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Study Chair: Carcelain Guislaine, PhD, APHP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2021

Primary Completion (Actual)

December 7, 2022

Study Completion (Actual)

December 7, 2022

Study Registration Dates

First Submitted

May 27, 2021

First Submitted That Met QC Criteria

June 7, 2021

First Posted (Actual)

June 8, 2021

Study Record Updates

Last Update Posted (Estimate)

March 3, 2023

Last Update Submitted That Met QC Criteria

March 2, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APH210217

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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