POS0063 CELLULAR IMMUNE RESPONSE TO THE ANTI-SARS-CoV-2 BNT162b2 mRNA VACCINE IN PEDIATRIC AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASE PATIENTS AND CONTROLS
Authors: T. Eviatar, T. Freund, A. Pappo, Y. Friedlander, O. Elkayam, A. T. Hiralla, D. Hagin, M. Heshin-Bekenstein
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Children with autoimmune inflammatory rheumatic diseases (AIIRD) are recommended to receive anti-SARS-CoV-2 vaccines. The data regarding the cellular immune response to BNT162b2 mRNA vaccine in pediatric AIIRD patients is scarce. <h3>Objectives:</h3> To compare the cellular response to BNT162b2 vaccine of pediatric AIIRD patients and healthy control. <h3>Methods:</h3> A prospective longitudinal study was conducted between April 2021 to December 2022 at the Tel Aviv Medical Center, Israel. Children under the age of 18, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 mRNA vaccine, were included. Blood samples were collected 2-8 weeks after the second vaccine dose. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 spike receptor-binding domain (RBD) antibodies, (SARS-CoV-2 IgG II Quant assay, ARCHITECT, Abbott). Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T-cells following stimulation with SARS-CoV-2 Spike peptide mix. Cellular and humoral responses, as well as breakthrough COVID-19 infections, and the correlation between these variables were compared between pediatric AIIRD patients and healthy controls. Differences between variables were tested using the independent sample T-test, Chi-square or the Fisher exact test, as appropriate. Pearson correlation was used to measure correlations. Cox-regression was used for survival models. <h3>Results:</h3> The study included 20 pediatric AIIRD patients and 11 controls with similar age and sex distribution. The mean age of all participants was 12.6±2.94 years, and 58.1% (n=18) were females. The AIIRD patients' diagnoses included 8 (40%) with juvenile idiopathic arthritis, 3 (15%) each of lupus, scleroderma, and uveitis, and 1 (5% each) with either vasculitis, myositis or inflammatory bowel disease with arthritis. The cellular response to the BNT162b2 vaccine was statistically similar in both groups, but numerically higher in the AIIRD children compared with controls (figure 1), as measured by calculated absolute number of CD4s staining positive for TNFα (median (range) 660 (0-2140) vs. 600 (0-1890), p=0.36), IFNγ production (380 (0-1700) vs. 280 (0-840), p=0.27), or both TNFα and IFNγ (465 (0-2900) vs. 390 (0-920) p=0.22), respectively. However, the humoral response, as measured by anti-RBD antibody levels, was statistically higher in the control group compared with AIIRD children (median (range) 34,837.9 (3716.7-40,000) vs. 6789.6 (243-23,274.7), respectively, p&lt;0.001). There was no statistically significant correlation between the humoral response and cellular response: TNFα R=0.097 (p=0.65), IFNƔ R=0.275 (p=0.193), co-production R=0.328 (p=0.1175). Although most participants showed a positive cellular response in all three parameters measured (IFN, TNF or co-production), one healthy control showed no cellular response, and another control had only an IFNγ response. One patient with uveitis treated with adalimumab did not respond by any parameter, another uveitis patient treated with methotrexate had only a TNFα response, and a third patient, with lupus, treated with hydroxychloroquine and eltrombopag for chronic thrombocytopenia, had only an IFNγ response. During the study period, 7 out of 16 (43.75%) AIIRD children (4 patients had COVID-19 before the first blood sampling and were excluded from this analysis) and 8/11 (72.7%) controls had a breakthrough COVID-19 infection (p=0.48). Univariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect of these variables (table 1). <h3>Conclusion:</h3> Compared to healthy controls, pediatric patients with AIIRD demonstrate a comparable cellular response, while they differ in their ability to produce anti-RBD antibodies in response to anti-SARS-COV-2 BNT162b2 mRNA vaccine. Even though children with rheumatic inflammatory diseases are also being treated with immunomodulation and may have an underlying immune dysregulation, they did not show an increased breakthrough infection rate. This may support the importance of the cellular response in COVID-19 infections. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> David Hagin and Merav Heshin-Bekenstein are equal contributors to this abstract. <h3>Disclosure of Interests:</h3> <b>None declared.</b>