AB0065 A LONGITUDINAL STUDY OF SARS-CoV-2 INDUCED HUMORAL AND CELLULAR IMMUNE RESPONSE IN IMMUNOCOMPROMISED PATIENTS AND HEALTHY CONTROLS

Background: Immunocompromised patients are particularly susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and previous findings indicate that the potency of the immune response triggered by either SARS-CoV-2 infection or vaccination against Coronavirus Disease-19 (COVID-19) diminishes over time. Objectives: Our main goal was to assess the SARS-CoV-2-specific immune response in immunocompromised patients and a cohort of healthy controls over more than one year. Methods: In this prospective longitudinal study, 84 rheumatoid arthritis (RA) patients and 43 healthy controls were recruited. Following peripheral blood collection, plasma samples were isolated. The SARS-CoV-2-specific serological response was evaluated by Elecsys Anti-SARS-CoV-2 Spike (S) immunoassay, and antibodies against SARS-CoV-2 nucleocapsid protein (NCP) were also measured by Euroimmun enzyme-linked immunosorbent assay (ELISA) test. The SARS-CoV-2-specific T-cell response was detected through an interferon-gamma (IFN-γ) release assay. Results: Our findings confirm the results of our initial report [1], revealing that individuals with RA show a markedly reduced anti-S antibody response and attenuated SARS-CoV-2-specific T-cell response compared to healthy controls even after a period exceeding one year. Moreover, our data demonstrate a significant augmentation in the SARS-CoV-2-specific humoral immune response during the follow-up period (p<0.05 for healthy volunteers, p<0.0001 for RA patients, rank-sum test), with anti-S concentrations several times higher than those measured during the initial period. Participants who received vaccination against COVID-19 in the interim period exhibited anti-S levels 2.72 times higher (CI 95%: 1.25-5.95, p<0.05) compared to those who remained unvaccinated. Individuals with confirmed SARS-CoV-2 infection showed 2.1 times higher anti-S levels (CI 95%: 1.31-3.37, p<0.01) than their non-infected counterparts during the interim period. Remarkably, patients treated with targeted therapy demonstrated approximately 52% lower anti-S levels (CI 95%: 0.25-0.94, p<0.05) compared to matched subjects who did not receive targeted therapy. Our analysis revealed that older individuals exhibited lower levels of anti-S antibodies (p=0.004). SARS-CoV-2-specific T-cell response levels did not change substantially in the study groups. However, SARS-CoV-2 infection during the interim period significantly enhanced the whole COVID virus-stimulated COVID-specific CD4+ and CD8+ (CW4-8) T-cell response by a factor of 2.09 (95% CI: 1.30 - 3.36, p<0.01) in RA patients. Conclusion: In contrast to initial expectations, our investigations revealed an increase in the magnitude of the SARS-CoV-2-specific humoral immune response over an extended period. Remarkably, the SARS-CoV-2-specific T-cell response exhibited relative stability in both study cohorts. This heightened humoral response, and the nearly permanent SARS-CoV-2-specific T-cell response might contribute to the reduction in severe COVID-19 cases in the population (Figure 1A, 1B). REFERENCES: [1] Nemeth, D. et al. (2022). Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis. Frontiers in immunology, 13, 960001. https://doi.org/10.3389/fimmu.2022.960001. Acknowledgements: This project was financed by the National Research, Development and Innovation Office Fund in Hungary (2020- 2.1.1-ED-2022-00198), the Thematic Excellence Programme (Tématerületi Kiválósági Program, TKP2021-EGA-29) of the Ministry for Innovation and Technology in Hungary, OTKA Grant (K 131479). This study was supported by the National Research, Development and Innovation Office of Hungary under the Investement in the Future funding scheme (2020-1.1.6-JÖVŐ-2021-00013) and by the grant of European Union RRF-2.3.1-21-2022-00003. TKP2021-EGA-23 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. Disclosure of Interests: None declared.