Risk factors for rejection following COVID-19 in lung transplant recipients

Introduction/Aim: The prevalence of and risk factors for acute cellular (ACR) and antibody mediated rejection (AMR) in lung transplant (LTx) recipients is unclear. Method(s): We performed a retrospective cohort study of all living LTx recipients between January 2020 and September 2022. Recipients with COVID-19 infection and those diagnosed with and/or treated for ACR or AMR were identified. Baseline demographics are described. A logistic regression univariate analysis was used to identify risk factors for rejection. Result(s): 128/387 (33%) LTx recipients tested positive to SARS-CoV-2 during the study period. 44 (32.3%) patients were investigated for graft dysfunction, with persistent loss of >=10% of FEV 1 at >=90-days in 37 (31.4%), median was 54.5 years (23-76). There was no significant difference between gender, disease severity or presence of chronic lung allograft dysfunction (CLAD) at time of COVID-19 infection. 9(20.5%) recipients experienced rejection, 3 (6.8%) with AMR, 5 (11.4%) ACR, and 1 (2.3%) both. Median time to onset of rejection was 59 days (16-239). Change in FEV 1 post COVID-19 was not significantly different between recipients with and without rejection, with mean volume loss in rejection group 559 mL (SD 678 mL, 22.9%), and 842 mL (SD 824 mL, 42.9%) in non-rejecters. Univariate logistic regression of risk factors demonstrated younger patients were at higher risk of rejection (OR 0.95 [95% CI 0.90-1.00] p = 0.05). Female gender was weakly associated with rejection (OR 0.21 [95% CI 0.04-1.18] p = 0.08). Time post-transplant, severe COVID illness, early COVID-19 treatment did not show association. Conclusion(s): Acute rejection occurs frequently following COVID infection and should be considered a differential in persistent allograft dysfunction. Younger age and female gender were associated with increased risk of rejection. The volume of lung function lost did not differentiate between those who did and did not suffer rejection;we hypothesise due to non-alloimmune inflammatory processes.

Relationship Between Covid-19 And Donor Specific Antibodies In Orthotopic Heart Transplant Recipients

Introduction: De novo donor specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection (AMR) and worse prognosis in patients after orthotopic heart transplant (OHT). Viral infections have the potential to induce or reactivate the production of DSAs, yet the development of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has not been reported. In this observational study, we describe DSA titers after Coronavirus Disease 2019 (COVID-19) infection and relationship with AMR and graft dysfunction in a large OHT cohort at a tertiary academic medical center. Hypothesis: : We predicted that COVID-19 infection would be associated with development of de novo DSAs or increase in pre-existing DSAs. Method(s): We retrospectively analyzed all adult OHT patients followed at Washington University School of Medicine in St. Louis between 4/1/2020-12/31/2021. COVID-19 infection was defined by positive antigen or PCR test in setting of clinical exposure or symptoms. Patients were considered fully vaccinated 2 weeks after 2 doses of the BNT162b (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines or after a single dose of the AD26.COV2.S (Johnson & Johnson) vaccine. De novo DSAs were defined as newly detected MHC I or II antibody greater than 2000 mean fluorescence intensity (MFI) by single antigen beads or newly elevated antibody against angiotensin-II type 1 receptor (AT1R). In patients with pre-existing DSAs, a significant increase was defined by an MFI value that increased by 20% or more compared to their baseline value prior to SARS-CoV-2 infection. Result(s): A total of 577 patients were followed during the study period and 117 cases of COVID-19 infection were identified. Baseline characteristics of COVID-19 positive patients are shown in Figure. Overall, 10% of patients infected with SARS-CoV-2 infection developed de novo DSAs or an increase in pre-existing DSAs, with unvaccinated patients having a higher incidence compared to vaccinated patients (15% vs. 2%, p=0.02). MHC class II-specific antibodies were the most common DSAs detected. There was a trend towards higher incidence of AMR in unvaccinated patients, although mortality and long-term graft dysfunction were similar. Conclusion(s): Unvaccinated patients had a higher incidence of developing de novo or an increase in pre-existing DSAs after SARS-CoV-2 infection. Future studies are necessary to investigate the long-term consequences of COVID-19 in the OHT population.Copyright © 2022

A Study of Long-Term Outcome of Mycophenolate Dose Modulation in Renal Allograft Recipients With SARS-CoV2 Infection During COVID-19 Pandemic

Introduction: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However, side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses.MMF dose reduction is required during its side-effects or co-existing infection in RTR.The outcome of MMF dose modulation in RTR is not well established. COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had Covid19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation Methods: We prospectively collected data of Renal transplant recipients developing covid 19 infection during the first and second covid waves. Management including decision on admission, immunosuppression modulation, antibiotics were done based on clinician's discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction, biopsy rate, biopsy proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels, development of DSA ( when done ), steroid increment were studied regression model. Kaplan - meier survival curves for 24 months drawn. Result(s): Among 251 renal transplant patients with SARS-CoV2 infection, 38 patients died during Index admission. 45 patients has not completed for 15 months.168 patients completed 15 month follow - up. Among them, anti-metabolite were reduced in 115 ( 68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( +/- 12.8) and 75.6 % had mild COVID. Median duration of follow-up was 18 months ( 14q1-22q3 months). Total Readmission rate was 66 ( 40.7%) (Group A 21( 50%) Vs Group B 45 ( 37.5 %). Graft Biopsy was done in 16% of patients. 9.3 % patients had acute rejection ( 11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1. Conclusion(s): MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow up is needed in any patient in whom MMF dose in manipulated No conflict of interestCopyright © 2023

Lung Transplantation in Patients with Irreversible Lung Injury Due to SARS-CoV-2: A Single-Center Experience

Background: Lung transplantation (LTx) has been demonstrated to be a feasible therapy in patients with irreversible lung injury due to SARS-CoV-2. Aim of this retrospective study was to present our experience with LTx in SARS-CoV-2 patients. Method(s): Records of the 136 patients who underwent LTx between January 2021 and August 2022 at our institution were retrospectively reviewed. LTx was performed in SARS-CoV-2 patients who showed radiological evidence of irreversible lung failure, after failed attempts of weaning off mechanical ventilation (MV) and ECMO;showed single-organ dysfunction;were SARS-CoV-2 negative, preferably <65 years old and awake under MV and ECMO support. Graft survival was compared between COVID-19 LTx patients and contemporary patients transplanted for other indications. Median follow-up amounted to 7.6 (5.2-14.5) months. Result(s): Among the 79 patients with SARS-CoV-2 lung failure referred for LTx, 9 (11%) patients were listed, 8 of them being transplanted between January 2021 and August 2022. One patient died while on the waiting list. All were on MV and ECMO support (awake in 6 cases) for a median ECMO support time of 75 (38.5-152.8) days. Four (50%) patients were male and median age was 52 (37-57) years. All patients underwent bilateral LTx on ECMO support that was weaned off in all patients at the end of Tx. After LTx, 2 (25%) patients showed a primary graft dysfunction (PGD) score grade 3 at 72 hours and required reinstitution of veno-venous (n = 1) and veno-arterial (n = 1) ECMO support that was successfully weaned after 7 and 6 days, respectively. One patient (12.5%) required rethoracotomy for bleeding, and two (25%) patients required new hemodialysis treatment, with recovery of renal function in all patients. Median MV time amounted to 8 days (1-30), median intensive care unit stay to 19 (13-26) days, and median hospital stay to 91 (62-103) days. No patient died in-hospital. At 1-year follow-up, graft survival was 100% in SARS-CoV-2 LTx patients and 95% for patients (n = 128) transplanted for other indications (p = 0.539). Conclusion(s): Lung transplantation in highly selected SARS-CoV-2 patients yielded excellent posttransplant results. Graft survival was comparable between patients transplanted for SARS-COV-2 pneumonia and patients transplanted for other indications. A multidisciplinary approach is of paramount importance to successfully bridge these patients to transplantation and to guarantee a complete patient functional recovery after transplantation.

Single Center Comparative Analysis of Abo Compatible Versus Abo Incompatible Kidney Transplant with Short Term 1 Year Follow Up

Introduction: Kidney transplantation is the best treatment option for patients with end-stage kidney diseases. Quality and longevity of life are better with kidney transplant than chronic dialysis. Kidney paired donation and ABO incompatible kidney transplant (ABOiKT) are among the strategies to expand the living donor pool to overcome shortage of organs. Although first ABOiKT done in 1951 by Hume et al. was an unsuccessful attempt;Alexander et al. in 1987, proposed desensitization protocol with successful ABOiKT. Advancements in desensitization protocols have resulted in increasing success with ABOiKT. In developing countries like India, numbers of ABOiKT are steadily increasing. Aim of this study was to assess short term outcome of ABOiKT and their comparison with ABO compatible kidney transplant (ABOcKT). Method(s): This was a single center prospective observational study done over a period of 2 years. All the living donor kidney transplants including both ABOcKT and ABOiKT done between September 2020 to August 2021 at Jaslok Hospital and Research Center, Mumbai were included in this study. All ABOiKT recipients underwent pre-transplantation desensitization with injection rituximab and plasmapheresis. Pretransplant isoagglutinin titer of <= 1 : 8 was considered acceptable. Inj. Antithymocyte globulin (ATG) (1mg/kg), Inj. Anti-T lymphocyte globulin (ATLG) (3 to 5 mg/kg) or Inj. Basiliximab (20mg 2 doses 4 days apart) was used as induction agent. Triple immunosuppression regimen of prednisolone, tacrolimus and mycofenolate mofetil was started 7 days prior to transplant in ABOiKT and 2 days prior to transplant in ABOcKT and continued in post-transplant period. Valganciclovir was given to all patients for Cytomegalovirus (CMV) infection prophylaxis for 6 months. All the transplant recipients were followed up at 0, 3, 6, 9 and 12 months after transplant and in between when clinically indicated. Data collected was analyzed at the end of 1 year for outcomes of rejection episodes, graft dysfunction, graft loss, infections and death. Result(s): Total 95 patients were included in study, 29 (30.5%) out of them were ABOiKT recipients. Mean (SD) age of study population was 37.8 (+/- 10.5) years. Blood group B to B was the most common ABOcKT and B to O was the most common ABOiKT. Highest baseline isoagglutinin titer was 1:1024.There was no significant difference for rejection episodes, graft dysfunction, graft loss and death in ABOiKT and ABOcKT groups. Urinary tract infection was the most common infection in post-transplant period. COVID-19 was most common viral infection followed by CMV infection. Bacterial infections and overall infections were significantly higher in ABOiKT recipients (p value 0.001 and 0.006 respectively) but severe infections requiring hospitalizations and ICU care were not significantly higher. Two deaths occurred during our study, one in each group. One death was related to COVID-19 infection and second was because of pulmonary mucormycosis. Conclusion(s): Contrary to belief, ABOiKT has non inferior short term outcomes when compared with ABOcKT. Though in our study, bacterial infections were significantly higher in ABOiKT recipients, severe infections requiring hospitalization and ICU care were not increased. ABO incompatible kidney transplantation is an effective modality to increase donor pool and can be applied more widely. No conflict of interestCopyright © 2023

Renal transplantation

Individuals with kidney failure face a future requiring long-term treatment with either dialysis or renal transplantation. Renal transplantation is the preferred form of renal replacement therapy, and is associated with a better quality of life, and usually increased longevity. Unfortunately, owing to excessive co-morbidities, only 30% of patients who develop end-stage renal failure are fit enough for transplantation. Over 90% of kidney transplants still function after 1 year, and most function for >15 years. Improvements in transplant outcomes are attributable to advances in histocompatibility testing, organ procurement, organ preservation, surgical techniques and perioperative care. Long-term outcomes have shown only minor improvements over the last two decades, although this should be considered in the context of deteriorating organ quality as older deceased donors with increasing co-morbidity are used more often to satisfy the need for donor organs. An overall increase in deceased donor numbers has boosted transplant activity in the UK, and it is hoped this will continue with the adoption of the 'opt-out' consent system. Living donor activity remains stable, but the use of non-directed altruistic donation and the living donor exchange scheme have reduced the need for higher immunological risk incompatible transplantation. The COVID-19 pandemic has reduced transplant rates globally, although national transplant systems are now recovering.Copyright © 2022

X-Ray Analysis of Donor Lungs within an Ex Vivo Lung Perfusion System (EVLP): A Pilot Study for the Assessment of the Brixia Score to Predict Transplantability

Background: Ex vivo lung perfusion (EVLP) is a safe and effective technique for lung evaluation and reconditioning of marginal donor lungs (DLs). The assessment of the DLs during EVLP is crucial for the transplantability decision making. There are a limited number of studies regarding the radiographic analysis of EVLP lungs. Furthermore, there are only few Xray grading scores available. The Brixia score is a proven radiological score for the severity grading of lung abnormalities with confirmed predictive power of the clinical outcome that was successfully used in pneumonia patients during the COVID-19 pandemic. It was the aim of our study to evaluate the X-ray findings of DLs within EVLP and investigate the prognostic potential of this score regarding transplantability and clinical outcome. Method(s): This is a retrospective observational pilot study. Between 2016 and 2022, a total of 277 double-lung transplantations (DLTx) were performed in our department. X-Rays of the last ten consecutive EVLP-DLs were blindly evaluated regarding the severity of interstitial and alveolar infiltrates and the Brixia score was calculated. Furthermore, the results (transplantability, severe primary graft dysfunction PGD, survival, hospital stay) and EVLP parameters (delta pO2) of these EVLP-DLs cases were analyzed and compared with the Brixia score for each case. Result(s): A range of Brixia score values from min 4 to max 18 was determined. Seven DLs were transplanted (mean delta pO 391 mm Hg, mean Brixia score 6.7) while three were rejected (mean delta pO 211 mm Hg, mean Brixia score 6). The two EVLP-DLs cases with the higher Brixia score (mean 15) were transplanted after EVLP. Postoperative PGD Grade 3 at 48 hours was recorded in one case without correlation to the Brixia score (Brixia score 4). All patients survived hospital discharge with a mean ICU and hospital stay of 9 and 30 days, respectively. Conclusion(s): In our pilot study, the Brixia score did not predict transplantability or postoperative function during EVLP. Additional studies are needed to further evaluate the use and clinical prognostic power of radiologic assessment with this or other scores in the EVLP lung assessment.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

A Single Centre Experience of Post Renal Transplant Infections in a Tertiary Care Centre in Eastern India

Introduction: In developing countries, Post renal-transplant infections is the leading cause of mortality, morbidity and decreased allograft survival. Our aims and objectives was to determine the incidence and prevalence patterns of clinically or microbiologically confirmed infection in the post renal transplant patients of our population and profiling of infections in relation to time period from the Transplant and the induction agent, also to develop strategies to counter risk of post transplant infection. Method(s): This was a retrospective observational study. Time period: January 2020- April 2022. Post renal transplant recipients presenting with infections (with informed consent) was enrolled in this study. Recurrent episodes of infection by different organisms in a same patient treated as a separate event. Data was tabulated using MS excel and all results projected in bar graphs, pie charts, histograms. Differences of quantitative parameters between groups were assessed using the t test(for data that were normally distributed) or nonparametric test (for data that were not normally distributed). Differences of qualitative results were compared using chi2 test. Kaplan-meier was used for survival analysis. P < 0.05 was considered significant. Result(s): 213 incidents of post renal transplant infections were documented in 148 patients between the study period. Of the 85 patients who underwent renal transplant(57 living donor and 28 cadaveric) in this time period 33(38.8%) patients presented with 42 incidents of infections. Majority (74.3%) : Males. Mean age: 36.3+/-5.6 years. Most common cause of native kidney disease was chronic glomerulonephritis(30%). 121 (81.7%) had living donor transplant and 27(8.3%) patients had cadaveric transplant. Induction agent was basiliximab in 97 patients (65.5%) had 133 infections (62.4%) and ATG was used in 51 patients (34.5%) had 80(37.6%) infections. In recent transplant (last 2 yrs) cases-In Basiliximab group: infection rate 4.1 in 100 patient months and in ATG group infection rate was 5.7 in 100 patient months. (p=0.28). 37.5%cases had infections with graft dysfunction most commonly AKI. Immediate post transplant infections (<1 month) were 34 (15.9%), most commonly UTI (44.11%) followed by pneumonia (15.9%). 48(%) infections occurred between 1-6 months, most commonly pneumonia(27.08%) followed by UTI(22.9%) and superficial fungal infection. Pulmonary tuberculosis was in 14 (6.6%) cases. 3 cases had disseminated TB. Infectious diarrhea was in 18(8.4%) cases, most common organism isolated was EAEC and EPEC. CMV colitis found in 3 cases. 27 (18.2%) patients had NODAT/PTDM. ParvoB19 was in 11(5.16%), CMV in 5 and BKVN in 3 cases. 41(19.2%) cases had severe sepsis requiring intensive care support. New baseline s.cr was achieved in 29.1% cases. Infection related death was 24(16.2%). COVID 19 infection was in 41 cases, 31.7% developed graft dysfunction and 18 (43.9%) required hospital admission due to moderate or severe disease. 2 patients had mucormycosis, one of them died after admission. [Formula presented] Conclusion(s): Profiling of infection in our centre is essential to formulate future strategies for infection control especially as the DDKT & ABOi KT is on the rise. Proper survillence, screening protocol, vaccination and patient education are essential to reduce the burden of post transplant infection and for better graft and patient survival. No conflict of interestCopyright © 2023

Inquilinus limosus Bacteremia in Lung Transplant Recipient after SARS-CoV-2 Infection.

Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.

New Aspects of Lung Transplantation: A Narrative Overview Covering Important Aspects of Perioperative Management.

The management of lung transplant patients has continued to evolve in recent years. The year 2021 was marked by the publication of the International Consensus Recommendations for Anesthetic and Intensive Care Management of Lung Transplantation. There have been major changes in lung transplant programs over the last few years. This review will summarize the knowledge in anesthesia management of lung transplantation with the most recent data. It will highlight the following aspects which concern anesthesiologists more specifically: (1) impact of COVID-19, (2) future of transplantation for cystic fibrosis patients, (3) hemostasis management, (4) extracorporeal membrane oxygenation management, (5) early prediction of primary graft dysfunction, and (6) pain management.

Unmasking of Immunoglobulin A Deposits Posttransplant due to COVID-19 AKI-Incidental or Causal - A Nephrologists' Dilemma A Case Report

COVID-19 is a global pandemic with the chronically immunosuppressed transplant recipients being the most vulnerable both to infection as well as complications of COVID-19. Here, we report a case of live-related renal allograft recipient who presented with complaints of loose stools and new-onset graft dysfunction 2 years posttransplant. He tested positive for COVID-19 infection. On allograft biopsy, there were significant immunoglobulin A (IgA) deposits with no evidence of rejection or ATN or crescents or significant chronicity. The initial pretransplant biopsy of the recipient had revealed chronic glomerulonephritis with nil deposits. The donor had no evidence of hematuria or hypertension and had a preserved GFR. We, therefore, considered the possibility of the unmasking of IgA deposits posttransplantation diagnosed in a recipient with COVID-19 infection. Copyright © 2022 Indian Journal of Transplantation.

Does the Use of High-Dose Corticosteroids in Renal Transplant Recipients during Long-Term Impact Covid-19 Have?

BACKGROUND: The long-term outcomes of renal transplant recipients (RTR) affected by SARS-COV2 infection are an unexplored area particularly given the heightened immunosuppression and post-COVID-19 sequelae and increased fungal infections. We aimed to analyze the patient and graft outcomes, infectious and non-infectious sequelae in RTR with COVID-19 over a long-term follow-up of 24 months. AIM OF THE STUDY: To analyze the patient and graft outcomes, infectious and non-infectious sequelae in RTR with COVID-19 over a long-term follow-up of 24 months. METHOD(S): This retrospective study included the RTR admitted during the two pandemic waves between March 25, 2020, and July 31, 2021. The survivors were followed for a maximum period of 24 months (till September 2022) and were studied for readmission rates, serious infection requiring hospitalization (SIRH), graft dysfunctions and biopsy-proven acute rejections (BPAR), patient and graft survival. RESULT(S): Of 251 RTRs with SARS-COV2 infection, 104 were treated during the first wave and 147 during the second wave. After an index mortality noted in 38 patients (15.1% - 11.5% in first wave vs 17.5% in second wave, P = 0.23), follow-up data of 213 patients were analyzed. 45 patients were lost to follow-up, and a complete follow-up data was available for 168 patients. A total of 70 patients (41.7%) required readmission with SIRH being the most common indication for readmission (19.6%) followed by rejection (8.9%). Patients who received high dose steroids during the COVID-19 illness had higher SIRH (32.4% vs 16%, p = 0.027). However, graft dysfunctions (13.5% vs 16%, p = 0.70) and the BPAR (8.1%vs9.2%, p = 0.84) were similar in both the groups. Overall mortality (5.4% vs 6.9%, p = 0.75) and graft loss (10.8% vs 5.3%, p = 0.23) were also similar at 24-month follow-up. CONCLUSION(S): The high-dose corticosteroid dosing in the RTRs during COVID-19 appears to be associated with increased infectious complications over long-term although the overall patient and graft survival was similar.

Immunosuppression Minimization Strategy for Abo Incompatible Kidney Transplant Recipients during Covid-19 Pandemic

BACKGROUND: In the presence of COVID-19 illness immunosuppressed patients such as kidney transplant recipients (KTRs) have a higher mortality risk. ABO incompatible KTRs (ABOi - KTRs) are high-risk transplants and the use of lowdose maintenance immunosuppression during the COVID-19 pandemic is unknown. AIM OF THE STUDY: To study effect of low dose maintenance immunosuppressive therapy on graft function and immunologic events in patients following ABOi-KTRs during COVID-19 pandemic. METHOD(S): We present the results of a follow-up study of eight ABOi-KTRs done in Kidney Transplant Unit at Jaslok Hospital during COVID-19 pandemic. RESULT(S): Seven (87%) of the eight patients were male, while one was female. The median age was 49 years. Prior to transplant, all patients received rituximab (500 mg) and plasmapheresis. Six (75%) patients received antithymocyte globulin (1 mg/kg) induction, while two (25%) received basiliximab. Dose of one immunosuppressive agent tacrolimus was decreased to trough level of 6 to 8 ng/ mL instead of 8 to 12 as compared to our institutional protocol in pre-covid era. Antimetabolites and steroids were used in usual doses. Although immunosuppression was decreased, no rejection episodes or infection observed up at 10 days, 1 and 3 month after discharge, and no significant changes occurred in creatinine level during same period. Acute graft dysfunction was seen in 1 patient and the severity was related to tacrolimus trough levels, which were higher. All patients recovered baseline kidney function with no mortality during follow-up. CONCLUSION(S): Our observational study suggests that the reduction of tacrolimus dose in ABOi KTRs performed during COVID-19 appears to be safe, since no patient experienced rejection episodes.

A Study of Long-Term Outcome of Mycophenolate Dose Modulation in Renal Allograft Recipients with Sars-Cov2 Infection during Covid-19 Pandemic

BACKGROUND: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses. MMF dose reduction is required during its side-effects or coexisting infection in RTR. The outcome of MMF dose modulation in RTR is not well established AIM OF THE STUDY: COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had COVID-19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation METHODS: We prospectively collected data of renal transplant recipients developing COVID-19 infection during the first and second covid waves. Management including decision on admission immunosuppression modulation antibiotics were done based on clinician'S discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction biopsy rate biopsy-proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels development of DSA ( when done ) steroid increment were studied regression model. Kaplan - Meier survival curves for 24 months drawn. RESULT(S): Among 251 renal transplant patients with SARSCoV2 infection, 38 patients died during Index admission. 45 patients have not completed for 15 months. 168 patients completed 15 month follow - up. Among them, antimetabolite were reduced in 115 (68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( i' +/- 12.8), and 75.6% had mild COVID. Median duration of followup was 18 months ( 14q1-22q3 months). Total readmission rate was 66 (40.7%) (Group A 21 (50%) Vs Group B 45 (37.5%). Graft biopsy was done in 16% of patients. 9.3% patients had acute rejection (11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1 CONCLUSION(S): MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow-up is needed in any patient in whom MMF dose in manipulated.

Covid-19 in Renal Transplant Recipients: Clinical Outcomes and Effect of Vaccination

BACKGROUND: COVID-19 has been associated with high morbidity and mortality in renal transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. The outcome following vaccination in renal transplant recipients is less reported. AIM OF THE STUDY: To assess effect of vaccination in renal transplant recipients with COVID-19 METHODS: We enrolled patients who underwent kidney transplantation at our center who tested positive for COVID-19 from the beginning of the pandemic till June 2022. Patients were screened for baseline and transplant characteristics functional parameters comorbidities immunosuppressive therapies vaccination status and treatment received. COVID-19 disease severity was assessed. Patients were followed up during the pandemic until June 2022 of those admitted or home quarantined via teleconsultation. Data was collected compiled and analyzed. RESULT(S): A total of 85 renal transplant recipients with COVID-19 infection were studied. The mean age was 42.5 years. Nine were not vaccinated, 11 had taken 1 dose of vaccination, and rest completed 2 doses of vaccination. 23 had received antibody cocktail, 65 survived, and 20 succumbed to COVID-19. A total of 48 of them had graft dysfunction, 22 had severe graft dysfunction requiring hemodialysis. Among those who expired only had received antibody cocktail, all of them had severe graft dysfunction and only 2 were not vaccinated. Among those who expired most expired in the second wave of the pandemic. CONCLUSION(S): Renal transplant recipients with COVID-19 have a high risk of mortality. Comorbidities like obesity, diabetes mellitus, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. Effect of vaccination and outcome of COVID-19 infection in renal transplant recipients is under reported. There is risk of severe COVID-19 infection despite vaccination. Therefore, safety preventive measures to be continued. More work needed to find a definitive treatment for COVID-19 infection and much more efficacious vaccines and vaccination strategies to be designed.

Factors effecting mortality among Covid-19 patients in Renal Transplant Recipients from a single center in Pakistan

Background. Corona virus disease-19 (Covid-19) has significantly affected organ transplantation with concerns regarding severe infection and mortality. Data on Covid-19 in renal transplant recipients (RTRs) is scarce from Pakistan. The aim of this study is find out the factors effecting mortality among Covid-19 patients in renal transplant recipients from the largest transplant center of Pakistan. Methods. All RTRs >18 years, with positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) and diagnosed as severe disease, between April to December 2020 were retrospectively reviewed. The severe disease was defined as O2 saturation < 94% at room air on admission. Survivors and non- survivors were compared. Demographics, immunosuppression, comorbid conditions, clinical features, laboratory investigations and graft function were noted. Results. A total of 95 RTRs had severe disease. There was no difference in mortality between age, gender and co-morbid conditions among survivors and nonsurvivors. Both groups received similar immunosuppressive regimen. Intensive care unit (ICU) admission [16.5% vs 68.8% p< 0.001 OR 11.17 95% CI (3.3-37.6)] and high D-dimers >1.5mug/ml (p=0.052) at the time of admission were significantly associated with mortality. There was no association of graft function with mortality. Treatment with methyl-prednisolone was found to be significantly associated with survival [83% vs 43% P=0.02 OR 0.15 95% CI (0.05-0.49)]. (Table 1) WHO grading of the disease is shown in figure 1, there was a 100% mortality among patients on mechanical ventilator. Conclusion. ICU admission and high D-dimers at the time of admission are the significant risk factors for mortality in patients with Covid-19 infection. There was no association of graft dysfunction with mortality. Steroids use has significantly improved survival in renal transplant recipients with severe Covid-19 infection.

Outcomes in Kidney Transplant Recipients With COVID-19 Illness in the Era of Vaccines

Background: Kidney transplant recipients (KTRs) are risk for severe complications from COVID-19 illness due to immunosuppression. Predating COVID-19 vaccines our center reported AKI in 39% & death in 13% of KTRs. Here we describe the impact of COVID-19 on allograft & patient outcomes in KTRs with & without COVID-19 vaccination. We also compare outcomes in KTRs with & without response (SARS-CoV2 spike/anti-S antibody) to COVID-19 vaccine. Method(s): This is a retrospective cohort analysis of 142 KTRs identified with COVID-19 illness between 7/1/21 and 2/10/22. We collected data on patient demographics, COVID19 vaccine doses, anti-S levels & clinical outcomes including graft dysfunction, hospitalization, ICU admission & death. Result(s): Of 142 KTRs in our cohort, 113 (80%) were fully vaccinated (+/-booster) and 29 (20%) were un or partially vaccinated. 60 of 113 vaccinated KTRs were tested for anti-S levels between COVID19 vaccination & illness: 68% tested positive and 32% negative for anti-S Ab. Allograft dysfunction & hospitalization were less frequent in fully vaccinated vs unvaccinated KTRs (Fig.1). There was no difference between the two in terms of ICU admission and death (22 vs 18%, p=0.7). Among vaccinated KTRs, there was a trend towards less graft dysfunction in positive vs. negative anti-S (15% vs. 33% p=0.15). No differences were observed between anti-S levels and hospitalization (23% vs 26% p=0.7), ICU admission (11 vs 60% p=0.07) and death (11 vs 20% p=0.65). Conclusion(s): In our cohort, kidney allograft dysfunction and hospitalization was less common vaccinated vs unvaccinated KTRs with COVID-19. Additionally, there is a trend towards lower graft dysfunction in those with positive anti-S Ab. No significant differences were observed in death and ICU admissions with vaccination or positive anti-S. Vaccination to COVID-19 and maintaining positive anti-S Ab (with boosters or monoclonal Ab) are important in preventing graft dysfunction and hospitalization following COVID-19.

Post COVID-19 Sequelae in Kidney Transplant Recipients (KTR): A Single Center Report

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, on KTR remains unknown. We aimed to determine the impact of COVID-19 illness on kidney graft function including graft loss and characterize Long COVID (LC) symptoms in KTR. Method(s): Clinical data were extracted from an established registry of KTR diagnosed with COVID-19 between February 2020 to April 2022. A LC symptom questionnaire was developed and distributed. KTR that self-reported COVID-19 associated symptoms >=2 months were considered to have Long COVID (LC). Result(s): Of the 121 post COVID-19 KTR, 15 (12%) developed graft dysfunction defined as an increase in serum creatinine >0.3 mg/dL. Characteristics of KTR stratified as with and without graft dysfunction are shown in Table 1. Urine albumin/creatinine ratio was higher in the group with dysfunction and 2 (1.6%) KTR lost their allografts as well. Four (18%) reported LC symptoms and the frequency of LC symptoms among the first 22 questionnaire respondents are shown in Figure 1. Conclusion(s): Both allograft injury and LC symptoms are frequent among KTR. Identification of risk factors for long-term complications post COVID-19 and development of mechanism-based interventions may mitigate post COVID-19 sequalae in KTR.

Transplant Graft TMA Injury Post COVID-19 Vaccination

Purpose: Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients who receive the mRNA type vaccines. Method(s): 48 year old male with end stage renal disease who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI-5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. Result(s): There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticleencapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. Conclusion(s): A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.