ABSTRACT
BACKGROUND AND AIMS Mortality due to SARS-COV-2 infection in hemodialysis (HD) patients and kidney transplant recipients(KTRs) is high. Despite increased rates of administration of two doses of mRNA vaccines among these vulnerable populations, the adequacy of the respective generated immune responses is reported lower than general population, especially in KTRs. A third booster dose has been officially recommended in these immunocompromised patients while the humoral and cellular immune responses to SARS-COV-2 vaccination remains to be elucidated in HD patients and KTRs. The aim of our study was to investigate the antibody (Ab) response status together with vaccine-induced alterations in circulating lymphocytes subsets, following the administration of three doses of the BNT162b2 vaccine in a cohort of maintenance HD patients and KTRs. METHOD The initial cohort of this prospective study (ClinicalTrials.gov, NCT04932876) included 34 HD patients and 54 KTRs who received two doses of the BNT162b2 (Pfizer–BioNTech). Of this cohort, 24 HD patients and 30 KTRs, who remained free of SARS-CoV2 infection and receive a third dose 6 months after the second dose, were finally analyzed. Lymphocyte subpopulations, including B cells, CD4+and CD8+T cells as well as naïve and memory T lymphocytes subpopulations among others, were analyzed by flow cytometry at four time points, before vaccination (T0), before the second dose (T1), 2 weeks after the second dose (T2) and 2–3 weeks after the third dose (T3). The anti-SARS-CoV2 antibody (Ab) response was assessed by using the ARCHITECT IgG II Quant test (Abbott). Titers >50 arbitrary units (AU)/mL were considered positive for seroconversion at T1 and at T2 and T3. RESULTS Of the initial cohort 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. Of the final cohort (24 HD and 30 KTRs), almost all HD patients (23, 96%) became seropositive since T2 and this finding remained at T3 (Figure 1). In KTRs the percentage of responders was doubled between T2 and T3, T2 9 KTRs (30%) versus T3 18 KTRs (60%) (Figure 1). KTRs who developed Ab at T1 ``respond'' better to the third dose, maximizing the levels of Ab. HD patients who became seropositive at T1 displayed higher CD19+B lymphocytes compared with their seronegative HD counterparts. In HD patients, a positive correlation was established between CD19+B cells counts and Ab titers at all time-points (P < 0.001). In KTRs, Ab at T1 showed an inverse correlation with T+B+NK at T1 (P = 0.006). T2-Ab showed inverse correlation with CD45RA+CD45RO at T0 (P = 0.01) and with CD3+at T3 (P = 0.02). T3-Ab showed positive correlation with CD3+CD16+56+at T2 (P = 0.003) and with CD3-CD16+56+at T3 (P = 0.01). CD19+at T3 correlated positively with Ab at T1 and T3 (P = 0.003 and P = 0.03, respectively). CONCLUSION Our study confirms the improved immunogenicity after the third dose of BNT162b2 vaccine in KTRs. The positive correlation between CD19+B cells and Ab in both groups of patients, more stable and constant in HD patients in comparison with KTR, possibly reflects successful humoral immunity. However, a big proportion of kidney patients remain at high risk for COVID-19 infection considering the new more transmissible variants such as the Omicron variant.
ABSTRACT
Background: The humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs. Materials and Methods: We included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2. Results: 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups. Conclusions: Our study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.