Risk factors associated with poor response to COVID-19 vaccination in kidney transplant recipients.
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ABSTRACT:
SUBMITTER: Azzi Y
PROVIDER: S-EPMC8413103 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Risk factors associated with poor response to COVID-19 vaccination in kidney transplant recipients.
Azzi Yorg Y Raees Harith H Wang Tao T Cleare Levi L Liriano-Ward Luz L Loarte-Campos Pablo P Pynadath Cindy C Ajaimy Maria M Alani Omar O Bao Yi Y Pirofski Liise-Anne LA Akalin Enver E
Kidney international 20210903 5
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| S-EPMC8475856 | biostudies-literature
Project description:IntroductionKidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients.MethodsTo analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response.ResultsSeventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses.DiscussionIn addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.
| S-EPMC9977967 | biostudies-literature
Project description:Background and aimImmune status profile can predict response to vaccination, while lymphocyte phenotypic alterations represent its effectiveness. We prospectively evaluated these parameters in kidney transplant recipients (KTRs) regarding Tozinameran (BNT162b2) vaccination.MethodIn this prospective monocenter observational study, 39 adult KTRs, on stable immunosuppression, naïve to COVID-19, with no protective humoral response after two Tozinameran doses, received the third vaccination dose, and, based on their immunity activation, they were classified as responders or non-responders. Humoral and cellular immunities were assessed at predefined time points (T0: 48 h before the first, T1: 48 h prior to the third and T2: three weeks after the third dose).ResultsResponders, compared to non-responders, had a higher total and transitional B-lymphocyte count at baseline (96.5 (93) vs. 51 (52)cells/μL, p: 0.045 and 9 (17) vs. 1 (2)cells/μL, p: 0.031, respectively). In the responder group, there was a significant increase, from T0 to T1, in the concentrations of activated CD4+ (from 6.5 (4) to 10.08 (11)cells/μL, p: 0.001) and CD8+ (from 8 (19) to 14.76 (16)cells/μL, p: 0.004) and a drop in CD3+PD1+ T-cells (from 130 (121) to 30.44 (25)cells/μL, p: 0.001), while naïve and transitional B-cells increased from T1 to T2 (from 57.55 (66) to 1149.3 (680)cells/μL, p < 0.001 and from 1.4 (3) to 17.5 (21)cells/μL, p: 0.003). The percentages of memory and marginal zone B-lymphocytes, and activated CD4+, CD8+ and natural killer (NK) T-cells significantly increased, while those of naïve B-cells and CD3+PD1+ T-cells reduced from T0 to T1.ConclusionsResponders and non-responders to the third BNT162b2 dose demonstrated distinct initial immune cell profiles and changes in cellular subpopulation composition following vaccination.
| S-EPMC10611345 | biostudies-literature
Project description:IntroductionComorbidities and immunosuppressive therapies are associated with reduced immune responses to primary COVID-19 mRNA vaccination in kidney transplant recipients (KTRs). In healthy individuals, prior SARS-COV-2 infection is associated with increased vaccine responses, a phenotype called hybrid immunity. In this study, we explored the potential influence of immune suppression on hybrid immunity in KTRs.MethodsEighty-two KTRs, including 59 SARS-CoV-2-naïve (naïve KTRs [N-KTRs]) and 23 SARS-CoV-2-experienced (experienced KTRs [E-KTRs]) patients, were prospectively studied and compared to 106 healthy controls (HCs), including 40 SARS-CoV-2-naïve (N-HCs) and 66 SARS-CoV-2-experienced (E-HCs) subjects. Polyfunctional antibody and T cell responses were measured following 2 doses of BNT162b2 mRNA vaccine. Associations between vaccine responses and clinical characteristics were studied by univariate and multivariate analyses.ResultsIn naïve KTRs, vaccine responses were markedly lower than in HCs and were correlated with older age, more recent transplantation, kidney retransplantation after graft failure, arterial hypertension, and treatment with mycophenolate mofetil (MMF). In contrast, vaccine responses of E-KTRs were similar to those of HCs and were associated with time between transplantation and vaccination, but not with the other risk factors associated with low vaccine responses in naïve KTRs.ConclusionIn conclusion, hybrid immunity overcomes immune suppression and provides potent humoral and cellular immunity to SARS-CoV-2 in KTRs.
| S-EPMC10928013 | biostudies-literature
Project description:BackgroundThere are limited data describing the immune responses to COVID-19 vaccination in pediatric kidney transplant recipients, and expanding upon this information could help inform vaccination strategies in this unique population.MethodsWe performed a prospective, observational, single-center cohort study using remnant blood samples of pediatric kidney transplant recipients from routine clinic visits to examine longitudinal serological responses after COVID-19 vaccination. We enrolled 61 pediatric kidney transplant recipients who had at least 1 sample available for analysis. Sera or plasma were analyzed for ancestral SARS-CoV-2 and Omicron (B.1.1.529; BA.1) spike IgG and nucleocapsid IgG using a Meso Scale Discovery platform.ResultsOne month after a 3-dose COVID-19 vaccination series, the IgG geometric mean titer to the SARS-CoV-2 ancestral spike was 684 binding antibody units/mL (95% confidence interval, 269-1739), but titers waned by 4-6 mo. A fourth dose of the COVID-19 vaccine boosted IgG geometric mean titer to 1606 binding antibody units/mL (95% confidence interval, 868-2972), and titers persisted through 6 mo. IgG titers against Omicron (B.1.1.529; BA.1) were overall lower than ancestral SARS-CoV-2. They were higher in participants with prior infection and were not significantly impacted by receipt of belatacept.ConclusionsAdditional doses of the COVID-19 vaccine bolstered durable serologic responses in pediatric kidney transplant recipients, and this study broadens our understanding of immune responses to COVID-19 vaccinations in this population.
| S-EPMC11809963 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a serious hazard for hemodialysis (HD) patients and kidney transplant (KTX) recipients as they suffer from an impaired immune response to SARS-CoV-2 vaccination. In addition, a definition of SARS-CoV-2 IgG titer that indicates a sufficient immune response, especially against new omicron variants, is urgently needed. In the present study, the immune response to either a third or a fourth dose of a mRNA vaccine was investigated in 309 dialysis and 36 KTX patients. SARS-CoV-2 IgG titer thresholds indicating neutralizing activity against wild type (WT) and the omicron variant BA.1 were quantified. After four vaccine doses, a high-neutralizing activity against WT was evidenced in HD patients, whereas the neutralizing rate against BA.1 was significant lower. Concerning KTX recipients, humoral and cellular immune responses after a third vaccination were still highly impaired. This calls for modified omicron-targeting vaccines.
| S-EPMC9785871 | biostudies-literature
Project description:BackgroundThe lower humoral immunity response after the COVID-19 vaccine in kidney transplant recipients (KTR) has been reported in several studies. However, there are few studies on the efficacy of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine compared between various immunosuppressive regimens.MethodsWe conducted a prospective cohort study at Siriraj Hospital, Bangkok, Thailand. Adult KTRs who received two doses of the ChAdOx1 nCoV-19 vaccine at intervals of 3 months were enrolled. Anti-SARS-COV-2 S-RBD-IgG antibody (anti-RBD) was assessed at the one month after the second dose and considered positive if the level ≥50 AU/mL or 7 BAU/mL. The primary outcome was the seropositivity of anti-RBD. The association between type, dose, and level of immunosuppressive regimen and anti-RBD seropositivity was analyzed.ResultsBetween October 2021 and January 2022, 139 KTRs with a median time of 55 months (IQR, 29-102 months), were enrolled. The mean age was 49.1 ± 11.3 years and 64.7 % were men. Seroconversion of anti-RBD was found in 72 patients (51.8 %). The seropositive rate was significantly higher in KTR who received tacrolimus (TAC)/everolimus (EVR)/prednisolone (CS) immunosuppression than EVR/mycophenolic acid (MPA)/CS and TAC/MPA/CS, respectively (95 % vs. 65 % vs. 34 %; p < 0.001). The MPA-containing regimen is associated with an inferior humoral response (OR 0.02, 95%CI 0.01-0.16; p < 0.001). In contrast, KTRs who received EVR had the highest immunogenic response (OR 12.97, 95%CI 4.69-35.84; p < 0.001). During the 11-month follow-up period, COVID-19 pneumonia occurred in 3 KTR in the seronegative group and none in the seropositive group.ConclusionThe anti-RBD response after ChAdOx1 nCoV-19 vaccination was revealed in 51.8 % of the KTR. KTRs who received the TAC/EVR/CS regimen had the highest immune response after vaccination, relatively comparable to the general population. The immunosuppressive regimen should be considered for a further vaccine dose in KTR.
| S-EPMC11808495 | biostudies-literature
Project description:The COVID-19 pandemic poses a significant risk for immunosuppressed groups such as transplant patients. The purpose of this study was to improve our understanding of the impact of the COVID-19 pandemic on kidney transplant recipients, including their views on COVID-19 vaccination. Semi-structured interviews were conducted from December 2021 to August 2022 with 38 kidney transplant recipients who had an appointment with their transplant care team within the previous 6 months. We used qualitative thematic analysis to characterize the perspectives of interviewees. Regardless of COVID-19 vaccination status, most interviewees reported utilizing public health measures such as masking, hand washing, and avoiding crowds to protect themselves against COVID-19. Vaccinated interviewees (n = 31) noted that they chose to receive a COVID-19 vaccine because of their increased risk due to their immunocompromised state. For unvaccinated interviewees (n = 7), reasons for not receiving a COVID-19 vaccine included concerns about the safety and efficacy of the vaccine. Both vaccinated and unvaccinated interviewees expressed concerns about the lack of adequate testing of the vaccine in transplant patients and questioned if the vaccine might have unknown side effects for transplant recipients. Regardless of the vaccination status, most interviewees noted having trust in their healthcare team. Interviewees also described interpersonal tensions that arose during the pandemic, many of which surrounded vaccination and other preventive measures that were important to participants to protect their health. Together, these data demonstrate differing concerns and experiences related to the COVID-19 pandemic for vaccinated and unvaccinated transplant recipients. These findings highlight the unique needs of transplant recipients and reveal opportunities to support this vulnerable patient population in efforts to protect their health as the COVID-19 pandemic evolves.
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