Heterogenous antibody and T‐cell responses to SARS‐CoV‐2 mRNA vaccines among immunocompromised young people

Abstract

Introduction: This study aimed to evaluate the humoral and cellular responses to SARS-CoV-2 mRNA vaccines in immunocompromised young people with kidney disease as their response is largely uncharacterized and vaccination recommendations have been extrapolated from adult practice. Methods: Immunocompromised patients (on corticosteroids, antimetabolites, calcineurin inhibitors, or with end-stage kidney disease) between 12-25 years old with kidney transplant, kidney failure, idiopathic nephrotic syndrome, IgA nephropathy/vasculitis, or systemic lupus erythematosus, were prospectively recruited with controls. Antibodies and T-cell responses (via interferon-gamma release assay) against the SARS-CoV-2 spike protein were quantified after 2 standard doses of SARS-CoV-2 mRNA vaccines. Results: 54 immunocompromised patients and 20 controls were recruited. 32 (59%) patients had anti-spike protein titers >250U/ml, compared to 20 (100%) controls (p=0.0003). Patients had reduced pan T-cell [-0.14±0.11 vs 0.24±0.09 logIU/ml, p=0.044] and CD4+ T-cell responses [-0.55±0.15 vs -0.003±0.09 logIU/ml, p=0.038] to spike protein compared to controls. There were differences in the proportion of antibody (p=0.014) and CD4+ T-cell responders (p=0.002) between disease categories (Table 1). On multivariable analysis, corticosteroids were associated with reduced humoral [OR=0.064 (95% CI:0.008-0.533), p=0.01] and to a lesser extent cellular responses, while calcineurin inhibitors were associated with reduced pan T-cell [-0.563 (95% CI: -1.106- -0.021) logIU/ml, p=0.042] and CD4+ T-cell responses [-0.903 (95% CI: -1.653-0.153) logIU/ml, p=0.019]. Interestingly, even after adjusting for immunosuppression through stratified analysis of patients on anti-metabolite monotherapy (n=28), there remained differences in pan T-cell (p=0.042) and CD4+ T-cells (p=0.045) responses between disease categories. Conclusions: Immunocompromised young people with kidney disease display attenuated responses to vaccination but there are significant differences between disease subgroups. This is partially due to differing immunosuppressant use, but is likely contributed by immune dysregulation inherent in these conditions. Patients with certain immune-mediated kidney diseases not on immunosuppression, e.g. IgA nephropathy, may benefit from a third primary mRNA vaccine dose.