Long-Term Immunological Memory of SARS-CoV-2 Is Present in Patients with Primary Antibody Deficiencies for up to a Year after Vaccination

Abstract

Some studies have found increased coronavirus disease-19 (COVID-19)-related morbidity and mortality in patients with primary antibody deficiencies. Immunization against COVID-19 may, therefore, be particularly important in these patients. However, the durability of the immune response remains unclear in such patients. In this study, we evaluated the cellular and humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in a cross-sectional study of 32 patients with primary antibody deficiency (n = 17 with common variable immunodeficiency (CVID) and n = 15 with selective IgA deficiency) and 15 healthy controls. Serological and cellular responses were determined using enzyme-linked immunosorbent assay and interferon-gamma release assays. The subsets of B and T lymphocytes were measured using flow cytometry. Of the 32 patients, 28 had completed the vaccination regimen with a median time after vaccination of 173 days (IQR = 142): 27 patients showed a positive spike-peptide-specific antibody response, and 26 patients showed a positive spike-peptide-specific T-cell response. The median level of antibody response in CVID patients (5.47 ratio (IQR = 4.08)) was lower compared to healthy controls (9.43 ratio (IQR = 2.13)). No difference in anti-spike T-cell response was found between the groups. The results of this study indicate that markers of the sustained SARS-CoV-2 spike-specific immune response are detectable several months after vaccination in patients with primary antibody deficiencies comparable to controls.

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies

“…A peripheral blood sample for SARS-CoV-2 anti-spike IgG was collected in a serum collection tube, centrifuged after 30 min, and frozen at −20 °C until the day of measurement. A sample for peripheral blood mononuclear cell (PBMC) isolation and phenotyping of B and T lymphocyte subsets was collected in a lithium heparin-coated tube, and PBMCs were isolated as described previously [ 25 ]. Samples for the assessment of CD4+ and CD8+ cell cytokine responses to SARS-CoV-2 peptide stimulation and cytokine determination before/after SARS-CoV-2 peptide stimulation were collected in heparinized whole-blood QuantiFERON SARS-CoV-2 blood collection tubes (Qiagen, Hilden, Germany), incubated at 37 °C for 20 h, centrifuged according to the manufacturer’s protocol, and frozen at −20 °C for subsequent analysis.…”

“…T and B cell subpopulations from freshly isolated PBMCs were determined by flow cytometry as described previously [ 25 ]. B cells were subdivided into the following subpopulations: naïve B cells (CD19+CD27−IgM+IgD+), marginal zone-like B cells (CD19+CD27+IgM++IgD+), switched memory B cells (CD19+CD27+IgM−IgD−), IgM-only memory B cells (CD19+CD27+IgM++IgD−), transitional B cells (CD19+IgD+CD27-IgM++CD38++), CD21low B cell (CD19+ IgM+,CD21-CD38-), plasmablasts (CD19+CD21+CD38+++IgM−), and atypical memory B cells (CD19+CD21−CD27−IgD−).…”

“…When the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic broke out in late 2019 [ 8 ], initial reports indicated increased disease-related morbidity and mortality in immunocompromised patients [ 9 , 10 , 11 , 12 , 13 ], including those with PAD [ 14 , 15 , 16 ]. After vaccines became available, several studies have investigated both the reactogenicity and immunogenicity of SARS-CoV-2 vaccines in PAD patients, and most studies concluded that the immune response in PAD patients was inferior to that in healthy vaccine recipients [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

“…Several studies with immunocompetent individuals have examined the correlates of SARS-CoV-2-specific humoral response and found changes in levels of M-CSF, IL-1α, IFN-γ, IL-1β, IL-10, IL-12p70, IL-6, IL-17A, IL-15, and IFN signaling-related cytokines (CXCL10, MCP-1, MCP-2, and MCP-3) to be correlated with SARS-CoV-2-specific antibody response in healthy volunteers [ 45 , 62 , 63 , 64 , 65 ]. Regarding PAD patients, several studies have examined the T cell response role in protection against SARS-CoV-2, showing IL-2 and/or IFN-γ secretion in response to pooled SARS-CoV-2 antigens [ 18 , 24 , 25 , 26 , 27 , 28 ]. Nonetheless, the understanding of the wider range of cytokines produced following SARS-CoV-2 antigen stimulation in individuals with predominantly antibody deficiencies is currently limited.…”

An Overview of the Immune Response to COVID-19 Vaccination and Strategies to Boost SARS-CoV-2 Immunity in People with Inborn Errors of Immunity

“…This is important because otherwise, known age-related changes in the immune system would confound the results of each study. The published study designs varied from observational [71,77,[83][84][85][86][87][88][89][90][91][92][93][94][95][96] to interventional studies and clinical trials [80,82,83,97,98]. Furthermore, humoral responses were reported by seroconversion, antibody concentration/titers, and, in some cases, virus neutralization/pseudo-neutralization capacity (Figure 3 and Table 2).…”