Senescent Lymphocyte Subsets Exhibit an Unexpected Advantageous Effect in the Response Against SARS-CoV-2 Vaccination in Dialysis Patients

ABSTRACT

Background: Vaccination against SARS-CoV-2 is a potent preventive tool against Covid-19. However, response to vaccination vary depending on comorbidities. This study evaluates clinical and immunological factors affecting humoral response of End-Stage Renal Disease(ESRD) patients to BNT162b2 Vaccine. Method(s) Humoral immunity was evaluated in 54 ESRD patients, by serum levels of anti-receptor-binding-domain (RBD) and neutralizing antibodies (Nab), measured by CLIA, 30 (T1), 60 (T2) and 120 (T3) days, after the second vaccine dose. Results were correlated to baseline patients' T and B-lymphocyte subpopulations as determined by flow cytometry. Result(s) Proportion of seroconverted patients based on Nab titer was diminished from 83.3%(T1) to 53.7%(T3), in three months. Age was negatively correlated to Nab at T1 and T2 (T1R=-0.334, p=0.027, T2R=-0.344, p=0.022). Patients on hemodiafiltration had higher Nab titers at T3. Presence of diabetes was associated with lower response rate, as 9/11 diabetics compared to 16/43 non-diabetics lost seroconversion at T3. Univariate analysis revealed a strong positive correlation of naive CD4 T-lymphocyte population with RBD at T1(R2=0.199, p=0.015) and with Nab titer at T3(R2=0.645, p<0.001), while no association was shown with naive CD8 T-lymphocytes. Nab titers at T3 were significantly correlated with late differentiated CD4 T-lymphocytes(R2=0.56, p<0.001) and EMRA CD8 T-lymphocytes(R2=0.156, p=0.017). Finally, RBD levels had a significant positive correlation with naive, and negative with memory B-lymphocyte count at T3(R2=0.147, p=0.031, R2=0.159, p=0.039, respectively). Conclusion(s) Age, diabetes mellitus and hemodialysis prescription have a strong impact to response to vaccination. T and B-lymphocytes phenotype are major determinants of humoral response potency to COVID vaccination with BNT162b2, in ESRD patients.