Background and research question:
Primary immune deficiencies (PIDs), also known as Inborn Errors of Immunity (IEI), are clinically characterized by an increased risk of severe infections. Therefore, these patients may also have an increased risk of adverse outcome of COVID-19 or may experience protracted course of disease. Effective SARS-CoV-2 vaccination would therefore be of great clinical importance in PIDs. However, until now not much is known about the efficacy and safety of SARS-CoV-2 vaccination in these vulnerable patients. In PID patients, the underlying disease may have a significant impact on the ability to develop an effective immune response after SARS-CoV-2 vaccination. Therefore this study aims to assess efficacy and safety of SARS-CoV-2 vaccination in patients with various forms of PID
PID patients show diminished B and T cell response after SARS-CoV-2 vaccination and these patients require intensified vaccination regimens
Prospective, controlled multicenter study
350 patients with an isolated antibody deficiency (175 patients with IgG subclass deficiency and 175 patients with SADNI),150 patients with either CVID, CID, CGD or XLA and 200 controls (partners or siblings of patients).
At baseline and after SARS-CoV-2 vaccination blood will be drawn at 4 different time points (baseline, at day 28, and 6 and 12 months post-vaccination). Nasal and oral swabs will be collected at baseline and in case of clinical signs suggestive for COVID-19 infection after vaccination. Questionnaires will be used to monitor for COVID-19 infection and disease outcome despite SARS-CoV-2 vaccination.
Primary endpoint is the antibody response in patients with an isolated antibody deficiency on day 28 after vaccination. Secondary endpoints include safety, monitoring of occurrence of infection despite vaccination, development of vaccine escape variants of the virus, durability of the immune response at 6 and 12 months and levels of SARS-CoV-2 specific T and B cell responses.
Patients with IgG subclass deficiency or SADNI versus controls: Due to underlying PID we expect a lower vaccination efficacy in patients with PADs than in controls. However, we consider a vaccination efficacy of 65% as clinically relevant, and therefore this is taken as the boundary for non-inferiority. Assuming an efficacy of 90% in controls and 65% in PID patients with a non-inferiority limit of 25%, with alpha 0.05 and beta 0.2, two groups including 172 participants per group are required to demonstrate non-inferiority.
Patients with CVID, CID, CGD and XLA: CVID, CID, CGD and XLA constitute of a heterogeneous group of clinical pictures. However, it is of utmost importance to better understand the response to SARS-CoV-2 vaccination in this vulnerable patient group. Therefore for these patients an explorative analysis will be performed to evaluate efficacy of SARS-CoV-2 vaccination in this patient cohort, to gain more insights in the per-patient response after vaccination. No power calculation can therefore be provided for this patient cohort.
A description of the participant population will be included in a statistical output report.
Participants who are seropositive to SARS-CoV-2 at baseline and participants who have not received at least one dose of the vaccine will be excluded from the immune response
analyses, including the primary analysis. All subjects who received at least one
administration of the vaccine will be included in the analyses of AEs.
Baseline characteristics of study participants will be reported for each patient cohort and control group. Continuous variables will be presented as mean ± standard deviation in case of a normal distribution or median (interquartile interval) in case of non-normal distribution. Categorical variables will be presented as numbers (percentage). Characteristics of each patient cohort will be compared with control groups using t-test or Mann-Whitney U-test (whichever appropriate based on variable di