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Purpose: Preliminary studies suggest that kidney transplant recipients (KTRs) show diminished humoral responses to SARS-CoV-2 vaccination. Although reports of allograft rejection after SARS-CoV-2 vaccination have been rare, there is no recommended framework for monitoring for potential vaccine-related allograft injury. Here, we describe an approach for longitudinal assessment of immunogenicity and safety of SARS-COV-2 vaccination in KTRs. Method(s): KTRs eligible for SARS-CoV-2 vaccination were identified through medical records, beginning March 12, 2021. Baseline and weekly blood samples were collected for SARS-CoV-2 spike protein antibody titers, dd-cfDNA and gene expression profiling (GEP) for 12 weeks. Donor specific antibody (DSA) testing was performed at baseline, 2 weeks after completion of vaccine doses and at week 12. Antibody response was defined as a 10-fold increase in total binding IgG titers. Result(s): 49 KTRs were identified for analysis. Patient demographics are shown in Table 1. Ten patients (20.4%) demonstrated a spike antibody response post- vaccination. Of responders, 80% (n=8) had a history of COVID-19. The odds ratio for the association of a history of COVID-19 with vaccine response was 18.3 (95% CI 3.2, 105.0, p=0.0005). Median dd-cfDNA levels did not differ between pre- and postvaccination (0.23% versus 0.21% respectively). There was no significant difference between pre- and post-vaccination GEP scores (9.85 versus 10.4 respectively). No patients developed clinically significant DSA, eGFR decline or allograft rejection following vaccination. Conclusion(s): Quantitative antibody responses were strongly associated with a diagnosis of prior SARS-CoV-2 infection. Stability of eGFR, dd-cfDNA, GEP profiles and lack of allosensitization reinforce the safety profile of SARS-CoV-2 vaccination in KTRs. Further studies are needed to better understand immunogenicity in SARSCoV- 2 naive individuals, including whether cellular responses are protective in the absence of humoral responses.
ABSTRACT
Purpose: Evolving data suggests booster vaccine doses enhance the immunogenicity of SARS-CoV-2 vaccines in solid organ transplant recipients with higher IgG responses, neutralizing antibodies titers, and greater SARS-CoV-2-specific T-cell counts. Currently, there is no recommended framework for monitoring potential vaccine-related immunological graft injury. Here, we describe kinetics of dd-cfDNA pre- and post-booster vaccination in kidney transplant recipients (KTRs). Method(s): Electronic medical records were reviewed to identify KTRs that received a SARS-CoV-2 booster vaccine dose in 2021 and were monitored with dd-cfDNA pre- and post-vaccination. dd-cfDNA was collected as part of standard of care assessment. Pre-booster dd-cfDNA levels were defined as the most recent result prior to booster administration. Post-vaccination results were collected up to 30 days post-booster administration. Result(s): 116 KTRs were identified for analysis. Patient demographics are summarized in Table 1. Median time from transplant to SARS-CoV-2 booster administration was 463 days (IQR 333-787.25, Table 1). Pre-booster dd-cfDNA levels were established a median of 9 days (IQR 2.25 - 16) pre-booster. The median level of dd-cfDNA pre-booster was 0.17% (IQR 0.12% - 0.25%). There was no significant difference in median levels of dd-cfDNA up to 30 days post-booster administration (Kruskal Wallis test with multiple comparisons, all p values >0.99, Figure 1). No adverse clinical events or acute rejection episodes were reported within 30 days of SARS-CoV-2 booster administration in this cohort. Conclusion(s): Median dd-cfDNA levels were not impacted by SARS-CoV-2 booster administration, suggesting that patterns of subclinical injury that may potentiate inflammation, allosensitization or allograft rejection are unlikely in this setting. The stability of dd-cfDNA demonstrated here further reinforces the safety profile of SARS-CoV-2 vaccine booster administration in KTRs.
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Purpose: Solid organ transplant recipients are at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19) with mortality rates as high as 30% reported in the early pandemic period. COVID-19 vaccine efficacy in the immunosuppressed population is lower than the general population. Early studies suggest that monoclonal antibody (MAB) treatment against the SARS-CoV-S spike protein may decrease hospitalizations and emergency department (ED) visits. Herein, we report our single center experience with use of MAB for COVID-19 treatment in kidney transplant recipients. Method(s): We performed a retrospective chart review of all kidney transplant recipients who developed COVID-19 from March 17, 2020 to January 26, 2022 at our transplant center. Date of diagnosis, vaccine status, MAB treatment, hospitalization and patient outcome was reviewed. Result(s): Two hundred ninety-one kidney transplant recipients had positive testing for SARS-CoV-2 in the period reviewed. 120 (41%) patients received MAB treatment. One patient death, not COVID related, was excluded from analysis. Of those who received MAB treatment, 99.2% survived compared to 82.4% of those who did not (p=0.00), Figure 1. Hospitalization was lower in those who received MAB (18.3% vs 60.8%, p=0.00). Completion of vaccine series, defined as 2 doses of mRNA or 1 dose of Janssen vaccine prior to infection, was also associated with better survival (98.6% vs 80.3%, p=0.00), Figure 1. Hospitalization rate was lower in those who completed vaccination prior to infection with SARS-CoV-2 (27.1% vs 59.2%, p = 0.00). The combination of MAB therapy and completion of vaccination also decreased hospitalization compared to those who received MAB but did not complete vaccines series (14% vs 26.8%, Table 1). Subgroup analysis of 143 patients infected from December 2021 to Jan 26, 2022 which may have reflected the Omicron surge was performed (Table 2). Treatment with MAB was associated with a reduction in hospitalization (11.6%) compared to 44.6% in those who did not receive MAB. Conclusion(s): MAB treatment for COVID-19 and prior vaccination were associated with improved survival and decreased risk of hospitalization in kidney transplant recipients.
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Purpose: Correlates of protection for SARS-CoV-2 vaccines are not well-established in kidney transplant recipients(KTRs). Studies have highlighted the importance of neutralizing antibodies(Abs), however data suggests T cell responses may play a secondary role in preventing reinfection. We performed a longitudinal assessment of immunogenicity, T and B cell response in KTRs following SARS-CoV-2 vaccination. Method(s): KTRs eligible for SARS-CoV-2 vaccination from 3/12/21 were enrolled. Baseline and weekly blood samples were collected for routine lab, SARS-CoV-2 spike protein Ab titers and cellular phenotyping for 12 weeks. Ab response was defined as a 10-fold increase in total binding IgG titers. To determine if T cell responses were induced by vaccination, we considered the proportion of activated non-naive CD4+ and CD8+ T cells post-vaccination. Result(s): 49 KTRs were enrolled ( Demographics -Table 1). 10 patients (20.4%) mounted an Ab response following vaccination. A history of COVID-19 was associated with an increased likelihood of developing an Ab response (OR: 18.3, 95% CI 3.2, 105.0, p=0.0005). For non-naive CD8+ T cells, a subset co-expressing CD38+Ki67+ was induced 1 week after the 1st immunization in some SARS-CoV- 2-naiive patients (P=0.12 versus P=0.14 for SARS-CoV-2-experienced adults, Fig 1A/B). For non-naive CD4+ T cells, induction of a subset co-expressing CD38+Ki67+ was observed at 1 week after the 1st immunization for SARS-CoV-2-naive participants (P = 0.09 for SARS-CoV-2-naive, P=0.03 for SARS-CoV-2-experienced adults, Fig 1C/D). For CD8+ and CD4+ T cells, dose 2 stimulated weak induction of the CD38+Ki67+ subset in the SARS-CoV-2-naive patients only (Fig 1A-D). Conclusion(s): Quantitative Ab responses were strongly associated with prior SARS-CoV-2 infection. Activated CD4+ and CD8+ T cell responses were evident in most patients irrespective of history of COVID-19. Further studies are needed to determine whether these activated CD4+ and CD8+ T cell responses were antigenspecific or confer immunity. (Table Presented).
ABSTRACT
SRTR data currently suggests that induction therapy in simultaneous heart-kidney transplantation (SHKT) with rabbit antithymoglobulin (ATG) provides survival advantage compared to interleukin-2 receptor antagonist (IL2-RA). We are reporting the outcomes of recipients with SHKT treated with IL2-RA as induction therapy. This is a single center, retrospective study of 26 patients who received SHKT at our institution from Dec 2018 to Oct 2021. A multidisciplinary team composed of heart and kidney transplant medical and surgical members determined appropriate recipient-donor SHKT candidate pairs. The majority of patients received IL2-RA induction therapy, and all patients received triple immunosuppression therapy with prednisone, mycophenolate mofetil and tacrolimus. Adjustments in long term therapy were made in collaboration between the heart and kidney transplant teams. From Dec 2018 to Oct 2021, 26 patients underwent SHKT. 23 patients (88%) were male, the median age was 57 years, and 5.4% were ≥ 65 years. 18 patients (69%) had non ischemic cardiomyopathy and 24 patients (92%) had CKD (mean GFR ≤ 35%). 18 patients were listed Status 2 and 2 patient Status 5. One patient received a DCD donor and 12 patients (46%) received hep C donors. 25 patients (96%) received induction therapy with IL2-RA. During the first 3 months post-transplant, the only patient who received ATG had 7 severe infections;11 patients (44%) and 13 patients (52%) who received IL2 -RA had no infections and ≤ 4 mild infections, respectively. One patient died due to COVID 19 pneumonia complicated by multisystem organ failure. For a median follow up period of 410 (187-707) days, 8% patients in the IL2-RA induction cohort experienced a 2R/3A heart rejection, 8% patients remained on HD due to primary kidney graft non-function, and the survival rate was 96%. Compared with present literature, our data support the use of IL2- RA as an induction strategy in SHKT with excellent patient survival. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Purpose: The rapid shift to telemedicine and remote monitoring of kidney transplant recipients (KTRs) during COVID-19 aimed to mitigate exposure risk for this vulnerable population. dd-cfDNA (AlloSure, CareDx Brisbane) is a well-established biomarker for surveillance of KTRs and is associated with allograft tissue injury, including immunological events such as acute rejection. Here we describe an innovative approach to remote surveillance for KTRs using mobile home phlebotomy during the pandemic. Methods: Pilot program of KTRs enrolled into the mobile home phlebotomy (RemoTraC) from March-November 2020. AlloSure dd-cfDNA was concomitantly performed with routine post-transplant laboratory studies at regular time intervals as per standard of care. Results: 159 KTRs were enrolled in the mobile phlebotomy program with 1421 draws completed during the surveillance period. Patient demographics are sum marized in Table 1. The median AlloSure dd-cfDNA level was 0.21% (IQR 0.12-0.42%). 25 for-cause biopsies were performed in patients monitored with mobile phlebotomy. 12 patients had biopsy proven rejections paired with AlloSure dd-cfDNA (1 borderline, 2 TCMR1A, 4 TCMR2A, 2 TCMR1B, 2 chronic active TCMR and 1 mixed AMR/TCMR). The median AlloSure dd-cfDNA was 0.5% (IQR 0.2-3.26%) in patients with active rejection compared to 0.14% (IQR 0.12-0.56%) in patients with no rejection (p=0.03). There was no difference in serum creatinine between the two groups (p=0.3). The median AlloSure dd-cfDNA levels in TCMR2A/1B and mixed AMR/TCR were 0.72 and 7.7% respectively. Conclusions: AlloSure dd-cfDNA can optimize post-transplant care by identifying patients at risk of allograft injury and rejection. This analysis demonstrates the feasibility of mobile phlebotomy for routine surveillance in combination with telehealth strategies during the unprecedented COVID-19 pandemic. In addition, utilization of dd-cfDNA helped clinicians direct limited resources during the pandemic for allograft biopsies when paired with standard clinical markers such as creatinine.
ABSTRACT
Purpose: COVID-19 infection is associated with 25% mortality in kidney transplant recipients (KTRs). Reduction of anti-metabolite immunosuppressants during the acute COVID-19 illness is a common approach in managing KTRs. This potentially increases the risk of allograft rejection in the setting of reduced immunosuppression. The optimal timing for safe reintroduction of immunosuppression remains unclear. Here we describe a novel approach of incorporating dd-cfDNA to safely titrate immunosuppression in patients with COVID-19. Methods: KTRs were monitored prospectively with dd-cfDNA beginning at the time of COVID-19 diagnosis or on discharge from acute care. If dd-cfDNA<1%, antimetabolite dosing was increased by 25% every two weeks. If dd-cfDNA>1% or a rapid relative change from baseline, antimetabolites were reintroduced at full dose provided the patient remained symptom free from COVID-19. Results: 58 KTRs (including 1 PAK) with COVID-19 infection were monitored with dd-cfDNA at the time of or following this diagnosis from March 2020 to January 2021. Demographics and directed treatments are summarized in Table 1. Median dd-cfDNA levels remained stable during longitudinal surveillance following COVID-19 (Figure 1A). 3/58 patients with COVID-19 and dd-cfDNA results available developed biopsy-proven rejection. One developed rejection at the time of COVID-19 diagnosis with elevated dd-cfDNA. 2/58 developed rejection in the setting of delayed re-introduction of antimetabolites due to clinical concerns (Figure 1B), however one did not have elevated dd-cfDNA. 10% of patients (n=6) had accelerated reintroduction of anti-metabolites due to dd-cfDNA levels>1% or rapid deviation from baseline. None of these patients developed rejection in the following months and dd-cfDNA levels decreased after immunosuppression reintroduction. Standard reintroduction of anti-metabolites with dd-cfDNA <1% was achieved with no associated episodes of rejection. Conclusions: dd-cfDNA presents a feasible adjunctive biomarker to guide immunosuppression titration in KTRs with confirmed COVID-19 and avoid allograft rejection during a time of increased immunological risk.