Responses to COVID19 Vaccination in Patients With a Treatment History of Rituximab.

Study Overview
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Brief Summary
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Patients with treatment history of rituximab since 01.01.2019 and immunocompetent volunteers will be contacted to give a blood sample after their COVID19 vaccination, and in a subset also before vaccination. Immune responses of antibodies and SARS-CoV2-specific T-cells to the vaccination will be quantified and the rituximab effect on COVID19 vaccine-induced immune responses is analyzed.

Official Title
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Registry Study for COVID19 Vaccination Efficacy in Patients With a Treatment History of Rituximab.

Conditions
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COVID19 Vaccination, Rituximab, Immunosuppression

Intervention / Treatment
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* Drug: History of exposure to anti-CD20 treatment since 01/01/2010
* Biological: Completion of COVID19 vaccine at least 4 weeks ago


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who were treated with anti-CD20 treatment since 01.01.2010 Patients who received a COVID19 vaccination (completion of all required doses) until target date (initial target: 30.05.21, but can be delayed to 30.06.21, 30.07.21 or 30.08.21 in case of insufficient enrollment) Volunteers without a history of anti-CD20 treatment exposure All: written informed consent. Exclusion Criteria: Exclusion criteria for patients (any of the following) Patients aged 18 years and younger at time of study enrollment and/or Pregnant or lactating women at time of study enrollment and/or Patients who do not provide written informed consent and/or Patients who have previously had a COVID19 infection (self-reported COVID19 disease, positive PCR or serology) Patients who are in a dependency relationship with the study personnel (hierarchical, social) Exclusion criteria for volunteers (any of the following) Volunteers aged 18 years and younger at time of study enrollment and/or Pregnant or lactating women at time of study enrollment and/or Volunteers who do not provide informed consent and/or Volunteers who suffer from an active autoimmune disease, active cancer, immunosuppressive therapy, history of anti-CD20 treatment and/or Volunteers who have previously had a COVID19 infection (self-reported COVID19 disease, positive PCR or serology) Volunteers who did not complete their COVID19 vaccination Volunteers who are in a dependency relationship with the study personnel (hierarchical, social)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Immunocompetent controls<br>Participants aged at least 18 years, no history of COVID19, no history of anti-CD20 treatment | Biological: Completion of COVID19 vaccine at least 4 weeks ago<br>* Completion of COVID19 vaccination course at least 4 weeks ago.<br>|
| Patients with a treatment history of rituximab<br>Participants aged at least 18 years, no history of COVID19, history of at least 1 dose of anti-CD20 treatment received since 01/01/2010 | Drug: History of exposure to anti-CD20 treatment since 01/01/2010<br>* Intravenous treatment history of anti-CD20 treatment since 01/01/2010<br>Biological: Completion of COVID19 vaccine at least 4 weeks ago<br>* Completion of COVID19 vaccination course at least 4 weeks ago.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response to SARS-CoV2 spike protein | Percentage of all patients developing IgG antibodies against SARS-CoV2 spike protein that is comparable to the immunological response in immunocompetent controls (-2 standard deviations of mean) | At least 4 weeks after completion of COVID19 vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of IgG antibodies against SARS-CoV2 with age, history, co-medication and biomarkers of immunocompetence | Multivariable regression models for IgG antibodies against SARS-CoV2 with age, history, co-medication and biomarkers of immunocompetence as confounding variables. | At least 4 weeks after completion of COVID19 vaccination | 
| Correlation of IgG antibodies against SARS-CoV2 with time interval since last dose of rituximab |  | At least 4 weeks after completion of COVID19 vaccination | 
| Correlation of IgG antibodies against SARS-CoV2 with cumulative dose of rituximab received. |  | At least 4 weeks after completion of COVID19 vaccination | 
| T cell anti-SARS-CoV2 response after COVID19 vaccination |  | At least 4 weeks after completion of COVID19 vaccination | 
| Correlation between IgG antibodies against SARS-CoV2 and B-cell counts, T-cell counts and total immunoglobulin levels | Multivariable regression models for IgG antibodies against SARS-CoV2 with B-cell counts, T-cell counts and total immunoglobulin levels as confounders. | At least 4 weeks after completion of COVID19 vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-cells, B-cells, COVID19 vaccine, SARS-CoV2, Rituximab