COVID-19 Infection and Acute Pancreas Transplant Graft Thrombosis.

The coronavirus disease 2019 (COVID-19) pandemic created an unprecedented challenge for healthcare, and the world continues to struggle in recovering from its aftermath. COVID-19 has been clearly linked to hypercoagulable states and can lead to end-organ ischemia, morbidity, and mortality. Immunosuppressed solid organ transplant recipients represent a highly vulnerable population for the increased risk of complications and mortality. Early venous or arterial thrombosis with acute graft loss after whole pancreas transplantation is well-described, but late thrombosis is rare. We herein report a case of acute, late pancreas graft thrombosis at 13 years post pancreas-after-kidney (PAK) transplantation coinciding with an acute COVID-19 infection in a previously double-vaccinated recipient.

SARS-CoV-2 Antibodies Transitions After Vaccination in Solid Organ Transplant Recipients: Multicenter Study in Japan

Purpose: For purpose of SARS-CoV-2 infection control, vaccination was started in worldwide, however, low reactivity of antibody production after vaccination is a concern for solid organ transplant (SOT) recipients. In general, antibody titers would be peaked within one month after vaccination for the healthy population, there are few report about SOT recipients vaccination. We explored antibody transitions in SOT recipients after vaccination. Method(s): A total of 641 solid organ transplant recipients were enrolled (481 kidney, 51 liver, 54 heart, 20 lung, and 35 simultaneous pancreas-kidney). All participants were administered the two-dose regimen mRNA vaccine (BNT162b2, Pfizer or mRNA-1273, Moderna), as indicated. SARS-CoV-2 antibodies were measured total 5 times throughout vaccination (Elecsys, Roche). Result(s): The antibody titer and positive rate were both elevated until three months and declined at six months after vaccination (positive rate;10.4%, 41.2%, 68.6%, 56.9%, in each) (Fig.1). Lung and kidney-pancreas transplant recipients showed poor antibody titer elevation compared with other organ transplantation (Fig. 2). Antibody titers be significant low by more than 60 years old compared with other ages (Fig.3). Conclusion(s): The antibody titer and positive rate transition of SOT recipients were quite different compared with the health population. The acquisition of antibody was different depends on type of SOT. (Figure Presented).

Adverse Renal Events After BNT162b2 Pfizer/BioNTech COVID-19 Vaccine in Kidney Transplant Recipients

Purpose: Adverse events of a novel mRNA vaccine are not well described in Kidney Transplant Recipients(KTR), especially the risk of immune activation or recurrent glomerulonephritis(GN), which has been described in native GN after COVID-19 vaccines. Method(s): In this single-center prospective study, 147 KTR were enrolled after informed consent and administered 2 doses of Pfizer/BioNTech vaccine 21 days apart. Follow-up was 3 weeks after Dose2. Result(s): Mean age of KTR was 51 years;55.1% male;65.3% Chinese, 19% Malay, 11.6% Indian;69.5% Living donor, 29.9% Deceased donor, 0.7% Pancreas-kidney transplants;71.5% had biopsy-proven or presumptive chronic GN(CGN), 12.9% diabetic nephropathy, 15.6% other causes. 11(7.5%) KTR had delayed Dose2 administered at median 29 days(range 24-93) after Dose1. 7(4.8%)were delayed due to renal events: rise in creatinine(n=3), or proteinuria(n=2), or both creatinine and proteinuria with allograft biopsy showing acute T-cell and antibody-mediated rejection(n=1), new BK viraemia(n=1). Other reasons were possible anaphylaxis(n=1), intercurrent infection(n=2), and inability to attend due to quarantine(n=1). 27 KTR had new microhaematuria(MH) after Dose1;9 persisted after Dose2. Additional 18 had new MH after Dose2. Of 45 KTR with new MH, 7 had underlying IgAN, 5 had other biopsy-proven-CGN and 22 had presumed CGN, suggesting 34/45 with possible immune activation. 12 KTR had new onset proteinuria (rise in urine protein:creatinine ratio (UPCR) <=30 to >30mg/mmol);5/7 who developed a rise after Dose1 remained elevated;additional 5 had a rise after Dose2. 7 KTR had rise in proteinuria from UPCR <=100 to >100mg/mmol. Conclusion(s): Subclinical changes in allograft monitoring parameters are frequent after COVID-19 mRNA vaccines with up to 40.1% of KTRs showing rises in creatinine, proteinuria or new MH. Although overt recurrent GN and acute rejection are infrequent, high vigilance and monitoring for these occurrences should be undertaken in KTRs receiving mRNA vaccines.

Hepatitis C (HCV) Positive Recipients and/or Donors in Pancreas Transplantation - A Registry Analysis

Purpose: Pancreas transplantation (PT) is the best long-term option for patients with labile diabetes and end-stage-renal disease. The mortality on the waitlist is high;patients should receive a transplant as early as possible. There remains a shortage of high-quality organ donors suitable for pancreas (and kidney) transplantation. PT in HCV positive recipients using a negative donor (R+/D-) has been performed but not vice versa (no R-/D+ transplants). After the advent of new, oral, and directacting antiviral agents, the option to use HCV+ deceased donor organs has become possible;anti-HCV treatment is started right after transplant. Method(s): All reported cases of R+/D- and R-/D+ transplants performed since 1/1/2019 were included in this study. Descriptive analysis of patient, donor characteristics, and outcome was performed. Patient and graft survival was assessed using the Kaplan-Meier method. Result(s): 38 R+D-, 36 R-D+, and 2 R+D+ transplants were identified. The majority were simultaneous pancreas kidney (SPK) transplants. Only one R-D+ pancreas after kidney transplant (PAK), and 8 pancreas transplants alone (PTA all R+D-) were performed. Tables 1 and 2 show donor and recipient characteristics for SPK transplants. The donors were excellent young donors, mostly males dying of trauma, but, in the R-D+ category, in the majority previous drug users. Notably, the waitingtime for R-D+ recipients was under 3 months in 50% of transplants. Outcome of the HCV NAT test at 6 months is shown in Table 3. The 2 positive patients at 6 months were negative at 1 year follow-up. Patient and graft survival is shown in Table 3. The 3 early deaths in the R-D+ group were 1 trauma, 1 bacterial infection due to technical problems, and 1 possible COVID-19 infection. All 3 patients died with functioning pancreas and kidney grafts. Conclusion(s): Pancreas transplantation is considered by many a non-life-saving procedure and, therefore, patients and donors are carefully chosen. What is neglected is the fact that the mortality of diabetic patients while waiting is high. Hence, it is essential to transplant as early as possible. In contrast to solitary pancreas transplants, the SPK waiting time is long. The advent of new HCV treatment modalities makes safe and successful transplants possible for HCV+ recipients and from HCV+ donors possible. HCV+ donors are usually young and excellent donors who fulfill acceptance criteria for pancreas transplantation. Follow-up time for patients in this study is short, but our preliminary results show that the use of an HCV+ donor results in safe and successful pancreas transplant outcome.

A Novel Approach to Post-Transplant Care of Kidney and Pancreas Transplant Recipients, Inpatient Level Care in the Home

Purpose: Demonstrate safe and cost effective care of early kidney and pancreas post-transplant complications through the Advanced Care at Home (ACH) inpatient home-based care program. Method(s): 5 abdominal transplant patients were admitted into ACH over a 1-month period. Each recipient underwent transplant less than a year prior to admission. These recipients received ACH and transplant standard of care including 24-hour access to a physician-led virtual monitoring center, telehealth and home-based provider visits, skilled nursing care, rehabilitation, nutrition, pharmacy, laboratory, imaging, social work, and other individualized healthcare services in the comfort of the patients own home. Result(s): 5 Recipients, all within 1 year of transplant were admitted with diagnoses of CMV Viremia, Bacteremia, AKI, pancreas rejection, COVID 19 and volume overload. Two patients required escalation back to the brick-and-mortar hospital, one for a biopsy to rule out rejection, the second for new onset sepsis and progressive renal failure requiring hemodialysis. A total of 33 brick and mortar bed days were saved, freeing hospital capacity during a time of critical bed shortage. None of the patients were re-admitted within 30 days of discharge from ACH. Conclusion(s): Advanced care at home is a safe alternative to the traditional Brick an Mortar(B &M) hospitalization for patients admitted with complications post abdominal solid organ transplant. We improved bed capacity in the midst of the COVID 19 pandemic and minimized cost associated with a traditional B & M stay.

An Analysis of Serological Response and Infection Outcomes Following Oxford Astra-Zeneca (azd1222) and Pfizer-Biontech (mRNA BNT162b2) SARS-CoV-2 Vaccines in Kidney and Pancreas Transplant Patients

Purpose: SARS-CoV-2 is associated with high mortality among transplant recipients. This study aims to compare the humoral responses between the Oxford-Astra- Zeneca(AZ) and BNT162b2(Pfizer-BioNTech) vaccines in transplant recipients Methods: We recruited 920 kidney and SPK transplant patients receiving at least one dose of SARS-CoV-2 vaccine excluding patients with virus pre-exposure. Serological status was determined using the COVID-SeroKlir ELISA (Kantaro-EKF). Patients with corrected antibody level less than 0.7AU/mL were considered seronegative. Result(s): 495 AZ and 141 Pfizer patients had a sample post-first and 593 post-second dose (346 AZ vs 247 Pfizer) analysed. Following the 1st dose 25.7% of patients seroconverted (26.6% AZ and 22.8% Pfizer). Post-second dose 42.8% of AZ patients seroconverted (148/346) compared to 52.6% of Pfizer (130/247, p=0.02, HR 1.48, CI 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have a significantly higher response than AZ patients (median 2.6 vs 1.78AU/ mL, Mann-Whitney p=0.005), still lower than the one observed in general population. Patients on mycophenolate had a reduced seroconversion rate (42.2% vs 61.4%, p=0.001, HR 2.17) and reduced antibody levels (0.47 vs. 1.22 AU/mL, p=0.001) and this effect was dose dependent (p=0.05). Prednisolone reduced the seroconversion rate from 58.2% to 43.6% (p=0.03,HR 1.8) among Pfizer but not AZ recipients. This result was internally validated in two time points. Regression analysis has shown that antibody levels were reduced by older age (p=0.002), mycophenolate (p=0.001), AZ vaccine (vs Pfizer) (p=0.001) and male gender (p=0.02). There was no difference on infection rate post 2nd dose among the two vaccines but 14/15 serious post-vaccine infections leading to admission occurred to patients who did not seroconvert. Conclusion(s): Both seroconversion and antibody levels are lower following AZ compared to Pfizer vaccinated transplant patients following two vaccine doses. Mycophenolate, older age, male gender are also factors affecting the antibody response. Serious post vaccine infections are limited to patients without antibody response. Transplant patients remain at serious risk of SARS-CoV-2 infection.

High Incidence of Anti-HLA DSA and Late Allograft Dysfunction in Solid Organ Transplant Recipients Hospitalized with COVID-19

Purpose: Solid organ transplant (SOT) recipients admitted for COVID-19 commonly experience immunosuppression reduction and acute allograft dysfunction. Given the number of SOT patients hospitalized for COVID-19, it is critical to understand the natural history of alloimmunity and allograft dysfunction in this population. Method(s): We prospectively enrolled SOT patients admitted with COVID-19 to our institution between January 1, 2020 and June 1, 2021 as well as a non-SOT control cohort. We collected anti-HLA antibody (HLA-Ab) and renal function data. We retrospectively reviewed donor-specific antibody (DSA) assignments in the context of each patient's transplant history and HLA typing. DSA that crossed the 1500 MFI threshold was classified as new DSA, and DSA that increased >1000 MFI was classified as increased DSA. For kidney transplant (KT) patients, we additionally evaluated renal function. The outcome of interest was change in serum creatinine (sCr) from pre-infection baseline to the most recent post-infection value. Baseline sCr was calculated as the median sCr in the year prior to COVID-19. For follow-up, the final sCr at least 60 days from COVID-19 was used. If the patient experienced allograft failure or the final sCr was >5.0 mg/dL, the final sCr was set equal to 5.0 mg/dL. Cumulative incidence of new or increased DSA was modeled with the Kaplan-Meier (KM) method. Group means were compared with one-way ANOVA using Tukey's multiple comparisons test. Result(s): We enrolled 129 hospitalized SOT patients: 82 (64%) with a KT, 27 with a liver transplant, and the remainder with a heart, lung, or pancreas transplant. Of the 86 patients who underwent HLA-Ab testing 10-180 days after COVID-19 diagnosis, 15 developed new or increased DSA (Fig. 1A). We then evaluated the 39 KT patients with HLA-Ab testing, a baseline sCr, and a late sCr measurement. At a median follow-up of 330 days, KT patients with new or increased DSA (in red, Fig. 1B) showed a significantly greater increase in late sCr than both non-SOT patients (in blue) and KT patients without new or increased DSA (in green). Conclusion(s): New or increased DSA following hospitalization for COVID-19 is common in SOT patients, with a KM-estimated incidence of 25% in the six months following COVID-19. In KT patients, this DSA is associated with poorer allograft function. These data suggest a role for more intensive surveillance in SOT patients convalescing from COVID-19. Further studies will be needed to elucidate the contribution of infection, immunosuppression, and other factors.

Response to COVID-Vaccination and Infection in Islet Transplant Recipients

Background: Since response to COVID-vaccine among transplant recipients remains diminished comparing to general population, we decided to assess effect of COVID-specifically among islet transplant patients. Methods: Response to COVID-infection and vaccine was assessed in a cohort of 20 islet transplant recipients: N=13 after islet transplant alone (ITx) , N=7 with islet after kidney (IAK) or pancreas after islet transplantation (PAI) . The median age was 48 years (25-62) . Maintenance immunosuppression included tacrolimus and an antimetabolite in addition to 5mg of Prednisone in IAK and PAI recipients. Nine patients received booster. Results: Seven patients (38%) chose not to be vaccinated and 4 (57%) of them remained COVID-free with no SARS-CV-2 Spike total antibody (Spike ab) present in their blood. The other three patients (43%) developed only mild symptoms of infection with a high level of Spike ab (>2,500 U/ml) afterwards. In contrast, all remaining 13 patients (62%) , who were vaccinated while on immunosuppression for a median of 7 years (0.5-16) , remained COVID-free (p=0.11, Fischer) . The level of Spike ab in response to vaccine varied: undetected- (N=4) , in range 1-100U/ml (N=6) , around 400U/ml (N=2) , and above 2,500U/ml (N=1) . Presence of 5mg of Prednisone did not affect the outcomes. Booster was administered in patients and increased the level of Spike ab above 100U/ml in all of them, in 7 (78%) to over 2,500 U/ml. One patient responded neither to vaccine nor to booster. There were no SAEs related to the vaccination or booster. Islet graft function remained stable in all but one patient after initial vaccination or COVID-19. Conclusion: Nearly half of unvaccinated islet transplant recipients developed Covid-19, however, all of them presented only with mild symptoms. In contrast, none of vaccinated transplant patients developed COVID-infection with 69% rate of seroconversion. Booster increased level of the Spike ab in those patients who responded to the original vaccination.

COVID-19 vaccination impact on presensitization status of patients awaiting pancreas and kidney/pancreas transplantation

Blood transfusions, pregnancies and previous organ transplantation can cause immunization. Infection and vaccination could alter the recipient sensitization status. Here we evaluated COVID-19 vaccination effect on presensitization status of Pancreas/Renal-Pancreas waitlisted patients in Pisa Hospital (Italy). We enrolled 27 patients (15 female and 12 male) which received a complete vaccination cycle (CVC) of COVID-19 mRNA vaccines (BNT162b2-Pfizer/BioNTech or mRNA-1273-Moderna);15/27 patients received third dose (booster). X-MAP technology (Luminex-beads) was used to identify class I and II anti-HLA antibody specificity. The population was studied before vaccination (BV) and 2 weeks after CVC and booster. Sensitivity status change (qualitative analysis) and mean fluorescence intensity (MFI) changes (semi-quantitative analysis) were calculated by Excel using specific functions created “ad hoc”: AntigenDifference() and AntigenValueSum(). We observed new specificities after CVC in 11/27 patients: class I (29%), class II (33%) and class I + II (22%);after the booster class I, class II and class I + II increased by 35%, 50% and 28%, respectively. No statistically significant differences were observed in the MFI mean value between CVC, booster and BV group (p > 0.05, Mann-Whitney U test). COVID-19 vaccination could induce changes in the percentage of circulating antibodies directed against HLA and should be considered in the pre-transplant risk assessment.

Determining Associations Between Dietary Vitamin D Intake and Episodes of Infection, Rejection and Length of Stay in Hospital in Kidney and Kidney-Pancreas Transplant Patients

Background: Vitamin D is a pleiotropic hormone and plays a major role in protecting the body against infection and regulating inflammation. Research suggests that kidney [K] recipients with low levels of 25 hydroxyvitamin D3 (25(OH)D3) have a higher incidence of infections and rejection. Furthermore, research indicates low dietary vitamin D intake is positively associated with a lowered 25(OH)D3 serum levels. However, no research exists examining vitamin D intake and length of stay in the hospital [LOS(H)] in the K and K-pancreas [KP] population. Objective: The objective was to determine the associations between dietary vitamin D intake and episodes of infection, rejection, and LOS(H) in K+KP transplant recipients. Methods: Methods: A prospective investigation of 110 K+KP transplant patients with follow-up at 3, 6, 9, and 12-months posttransplant was undertaken. Due to barriers encountered by the COVID-19 pandemic, data was collected at baseline and 3 months only. Dietary vitamin D intake was obtained through modified Automated Multi-pass Method 24-hour (24HR) dietary recall at baseline which were analyzed by ESHA Food Processor. Vitamin D intake amounts did not include intake from supplementation. Episodes of infection, rejection and LOS(H) were recorded at 3 months post-transplant. Demographic data was determined using frequencies and means ± SD. Associations were determined using Spearman's correlations. Statistical analysis was preformed using SPSS v27 and statistical significance was determined using p < 0.05. Results: Results/Discussion: 100K and 10KP were available for evaluation. Participants were 64% male and 36% female, mean age: 50.5 ± 13.9 years, and BMI: 28.6 ± 5.5kg/m2. 99% of our patient population did not meet their recommended dietary allowance [RDA] for vitamin D intake by food alone, thus, it is possible that a portion of our patient population would have deficient serum 25(OH)D3 levels. No significant associations were found between vitamin D intake and episodes of infection, rejection, or LOS(H) at 3 months. We report 25% vitamin D intake from dairy products and only 2% from margarine. Lower intake of dairy products may be related to the recommendation of a potassiumrestricted nutrition care plan in the K+KP population. Conclusion: Conclusion: We report no association between vitamin D intake and episodes of infection, rejection, or LOS(H) likely due to the fact that the majority of our population's dietary intake did not meet vitamin D intake recommendations. Our future research will focus on improving patient vitamin D intake, supplementation and investigating 25(OH)D3 levels in association with episodes of infection, rejection, and LOS(H).

The course of the novel coronavirus infection COVID-19 in recipients of solid organs, depending on the type of maintenance immunosuppression according to the local transplant register

Background. The novel coronavirus infection COVID-19 has had a significant impact on organ transplantation in the world, both by reducing the availability of deceased donor organs due to the overload of intensive care units with patients with viral pneumonia, and due to the severe course of infection in patients after transplantation secondary to maintenance immunosuppression. The composition of maintenance immunosuppression in a patient after transplantation may affect the course of coronavirus infection. Study purpose. Based on the local transplant Register analysis, determine the effect of the composition of maintenance immunosuppression on the outcome of COVID-19 in organ transplant recipients. Material and methods. In March 2020, due to the COVID-19 pandemic, additional blocks characterizing the COVID-19 in a patient were introduced into the modules of the Register. The analytical section of the Register allows to compare the results of transplantation in patients' groups arbitrarily formed by the researcher. Daily updating of data allows to analyze actual information. An analysis of COVID-19 outcomes in recipients of donor organs is carried out depending on the composition of maintenance immunosuppression. Results. Between February 2020 and April 2021, the Register identified 72 recipients with COVID-19, of them 41 were on steroid-free immunosuppression. Recovered 93% of steroid-free patients and 48% of steroid based patients, mortality rate was 5 vs 42%, graft loss was 2 vs 10%. Conclusion. The Transplant Register, which exists in the legal field of Russian legislation, taking into account information about transplants performed in specific medical centers to specific patients, their effectiveness, including the practice of their rehabilitation and medical support, allows timely identification of successful practices, including in new conditions arising in connection with the COVID-19 pandemic. Maintenance immunosuppression without steroids significantly increase the chances of a favorable outcome of COVID-19 in organ transplant recipients. © 2021 GEOTAR Media. All rights reserved.

COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity.

BACKGROUND: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. METHODS: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. RESULTS: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1-150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015-0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007-0.906) p = 0.041) were protective. CONCLUSIONS: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.