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

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.

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".

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.