Abstract

BackgroundWhile serological assays detecting antibodies in blood serum remain the standard exam for evaluating immunity against SARS-CoV-2 infection, the latest publications reveal certain limitations to this broadly used method. Recent studies showing the decline of antibodies titers in time, together with scientific reports which detect SARS-CoV-2-specific T-cells in seronegative individuals, evoke questions with regard to the reliability of the sole assessment of the humoral response to SARS-CoV-2. A novel T-cell-based Interferon-γ Release Assay (IGRA) is proposed to adapt our approach to the individual immunity to the new coronavirus.ObjectivesThe objectives of this study were to assess T-cells and antibodies responses to the SARS-CoV-2 virus among pediatric patients at different stages of juvenile idiopathic arthritis (JIA) undergoing diverse treatment regimes. In addition, the authors aimed to evaluate humoral and cellular responses to the Covid-19 mRNA vaccine in the cohort of immunocompromised patients.MethodsThis prospective study included 30 pediatric patients between the ages 2-16 at different stages of JIA. The cohort group consisted of vaccinated and unvaccinated individuals and children with both positive and negative history of past Covid-19 infection. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood, followed by anti-SARS-CoV-2 ELISA test measuring the presence and quantity of IgG, IgM and IgA antibodies in serum.ResultsThe magnitude of the SARS-CoV-2 specific T-cell response measured by the IGRA test correlated significantly with the levels of IgG (p<0.00005, R=0.653) and IgA antibodies (p<0.00001, R=0.675) in serum, while no correlation with IgM antibodies level in serum was found. All vaccinated patients developed a cellular response to the vaccine (p=0.0108), regardless of the number of administered doses. The T-cells response in children undergoing biological treatment (specifically: etanercept, adalimumab or tocilizumab) was recognizably weaker compared to the group not receiving such treatment. Nevertheless, the difference did not reach statistical significance (p=0.0715). Similar dependencies were found in children treated with hydroxychloroquine (n=6), however, due to the small study group, a statistical significance could not have been reached.ConclusionSuppression of cellular response observed in different drug protocols may prove to become a protective factor against SARS-CoV-2 infection. Additionally, the authors postulate that the strong correlation found between T-cell response and IgA antibodies titer can be related to SARS-CoV-2 strong affinity with mucosal membranes. Thus, the sole testing of IgG and IgM antibodies levels in serum with regard to Covid-19 may not be the most precise diagnostic method. The presented study group needs to be expanded with more patients, mainly children receiving biological agents or hydroxychloroquine to validate the demonstrated preliminary results.

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