Lung re-transplantation for COVID-19 related respiratory failure: A case report

Objectives: We would like to report a case in which a COVID-19 patient who was transferred to our hospital due to a lack of medical resources due to the COVID-19 outbreak in Daegu, South Korea, on February, 2020, underwent double lung transplantation after 110 days with VV-ECMO support and performed double lung re-transplantation 865 days after lung transplantation. Method(s): ECMO was performed on a total of 69 patients with COVID-19-related acute circulatory/ respiratory failure from February 2020 to December 2022. Among them, 16 patients were registered for lung transplantation, and 5 out of 16 registered patients performed lung transplants. One in five people who performed lung transplantation performed retransplantation on the 865thday after transplantation. Result(s): A 52-year-old female patient was transferred to our hospital, and VV-ECMO was performed the next day. The double lung transplantation was performed 112 days after hospitalization and was discharged 238 days after surgery. 668 days after lung transplantation, home O2 was applied as bronchitis obliterans syndrome, and her lung function deteriorated rapidly later, and re-transplantation was decided. In the patient;s HLA test, HLA class I cPRA% was 32% and HLA class II cPRA% was 100%. Desensitization was performed six times plasmapheresis with administrating Botezomib and immunoglobulin, and then re-transplantation was performed on the 865th day after lung transplantation. The patient has maintained her daily life without any special complications other than the occurrence of central DI after surgery. The pathological findings of the lung previously transplanted to the patient were acute rejection (ISHLT grade A2), chronic airway rejection (ISHLT grade C1, B0), and chronic vascular rejection (ISHLT grade D1). Conclusion(s): The long term result of patients who performed lung transplantation with COVID 19 related respiratory failure is still unknown. Therefore, even patients who have undergone long-term VV-ECMO support due to COVID 19 related respiratory failure are expected to achieve good results if lung transplantation is needed by carefully approaching and treating with a multidisciplinary approach.

Social Attitude Towards COVID-19 Vaccine 1 Year After the Pandemic

Objective: To increase vaccine awareness, we aimed to determine individuals' knowledge and behavioral approach to the COVID-19 vaccine.Methods: The data of this cross-sectional study were obtained online between June and July 31, 2021. One thousand one hundred seventy-six people over the age of 18 were included in the study. The researchers developed a data collec-tion form consisting of 27 questions. Mean +/- standard deviation and median (1st quarter-3rd quarter) values, numbers, and percentages were used to summarize the data. Chi-square (chi 2) test was used to show the relationship between categorical variables. Independent predictors of participants' vaccine hesitancy/rejection were analyzed using logistic regression. Statistically, data withp<0.05 were considered significant.Results: A total of 1176 people, 55.7% of whom were women, with a mean age of 39.75 +/- 11.27 years, were included in the study. 71.6% of the participants were married, and 78.9% had a university/postgraduate degree. 9.7% of the partic-ipants stated that they were hesitant about the COVID-19 vaccine, and 7.1% refused the COVID-19 vaccine or would not be vaccinated when it was their turn. According to the logistic regression model established to examine the factors that may affect vaccine rejection;Age, the resources used to obtain information about the vaccine, the thought that it would not protect for two years, or the vaccine side effects were high, and the most effective way to get rid of the pan-demic was not vaccination, were determined as the factors affecting vaccine rejection.Conclusion: As a result of the research, it was found that the participants had a positive attitude towards the COVID-19 vaccine. It was determined that 9.7% of the study group had vaccine hesitancy, and 7.1% had vaccine rejection.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

BACKGROUND: The optimal treatment for chronic active antibody-mediated rejection (ca-AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL-6, has been proposed as a therapeutic option. We reported our experience treating ca-AMR with TCZ either as the first line option or as a rescue therapy. METHODS: We studied 11 adult kidney transplant recipients with biopsy-proven ca-AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd-cfDNA. Clinical monitoring included dd-cfDNA and DSA testing every 3 months during the treatment with TCZ. RESULTS: In this cohort, ca-AMR was diagnosed at a median of 90 months (range 14-224) post-transplant, and 4 of 11 patients had DSA negative ca-AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd-cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd- cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd-cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections. CONCLUSIONS: In our early short-term experience, TCZ appears to reduce graft injury as measured by dd-cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.

Challenges in Assessing COVID-19 Vaccines Safety Signals-The Case of ChAdOx1 nCoV-19 Vaccine and Corneal Graft Rejection.

The rapid and large-scale roll-out of new COVID-19 vaccines has led to unprecedented challenges in assessing vaccine safety. In 2021, the European Medicines Agency (EMA) processed about 1.7 million safety reports related to COVID-19 vaccines in the EudraVigilance (EV) database and identified more than 900 potential signals. Beyond the large amount of information to be processed, the evaluation of safety signals has faced several difficulties and limitations, both in the assessment of case reports and in the investigation of databases. The evaluation of a signal of corneal graft rejection (CGR) with Vaxzevria® was no exception to this. In this commentary, we present the challenges encountered in making regulatory decisions in the context of evolving evidence and knowledge. The pandemic crisis emphasised the importance of quick and proactive communication to address the many questions and, above all, to ensure the transparency of safety data.

Academic Framing of Computational Representations in the Virtual Classroom during Covid-19

Keywords: Agenda;Framing;Social representations;Expectations;Computer Introduction The development of research projects often requires the competition of computers, software and data analysis techniques, but the acceptance, appropriation and intensive use of them presents limitations in terms of utility and risk expectations [1]. Some explanatory models of human capital formation suggest that the formation of talent or intellectual capital in intangible assets of organizations is due to habitus [3]. [...]the predictive models of the social representations of these determinants have not been observed in the explanation of the relations with the intensive use of technologies, devices and electronic networks. [...]the objective of the present work was to establish the academic link relative to the social representations of computer computers, considering the dimensions of the organizational, educational and cognitive models. Methodology A documentary, retrospective and exploratory study was carried out with a selection of sources indexed to international repositories Table 1, considering the indexing period from 2019 to 2021, as well as the search by allusive keywords for negative (stigma, risk, rejection) and positive (utility, acceptance, appropriation) (Table 1) Content analysis and opinion matrices were used, considering the inclusion of findings, ratings and comparisons of coded data such as;-1 for negative dimensions (stigma, risk and rejection) and +1 for positive dimensions (utility, acceptance and appropriation) The qualitative data analysis package was used, considering equation (1) in which the contingency relations and the proportions of probabilities of taking risks in permissible thresholds of human capital formation stand out The contrast of the null hypotheses was made from the estimation of these parameters.

Social Attitude Towards COVID-19 Vaccine 1 Year After the Pandemic

Objective: To increase vaccine awareness, we aimed to determine individuals' knowledge and behavioral approach to the COVID-19 vaccine. Methods: The data of this cross-sectional study were obtained online between June and July 31, 2021. One thousand one hundred seventy-six people over the age of 18 were included in the study. The researchers developed a data collection form consisting of 27 questions. Mean +/- standard deviation and median (1st quarter-3rd quarter) values, numbers, and percentages were used to summarize the data. Chi-square (chi(2)) test was used to show the relationship between categorical variables. Independent predictors of participants' vaccine hesitancy/rejection were analyzed using logistic regression. Statistically, data with p<0.05 were considered significant. Results: A total of 1176 people, 55.7% of whom were women, with a mean age of 39.75 +/- 11.27 years, were included in the study. 71.6% of the participants were married, and 78.9% had a university/postgraduate degree. 9.7% of the participants stated that they were hesitant about the COVID-19 vaccine, and 7.1% refused the COVID-19 vaccine or would not be vaccinated when it was their turn. According to the logistic regression model established to examine the factors that may affect vaccine rejection;Age, the resources used to obtain information about the vaccine, the thought that it would not protect for two years, or the vaccine side effects were high, and the most effective way to get rid of the pandemic was not vaccination, were determined as the factors affecting vaccine rejection. Conclusion: As a result of the research, it was found that the participants had a positive attitude towards the COVID-19 vaccine. It was determined that 9.7% of the study group had vaccine hesitancy, and 7.1% had vaccine rejection.

Research highlights on kidney transplantation in 2021: Voices from China

Over the past 70 years, kidney transplantation has become not only the most mature but also the highest-success-rate surgery among all organ transplantation surgeries. However, the long-term survival of kidney transplant recipients is still challenged by such key factors as ischemia-reperfusion injury related to kidney transplantation, rejection, chronic renal allograft dysfunction, renal allograft fibrosis, immunosuppressive therapy, infections and others. Relevant fundamental and clinical studies have emerged endlessly. At the same time, the research related to kidney transplantation also becomes a new hot spot accordingly in the context of the normalization of novel coronavirus pneumonia. This article reviewed the cutting-edge hot spots in relation to the fundamental and clinical aspects of kidney transplantation together with relevant new techniques and new visions. The studies included in this article focused on the reports published by Chinese teams that are more applicable to the current situation of kidney transplantation in China, for the purpose of providing new thoughts and strategies for the diagnosis and treatment of kidney transplantation related issues in China.Copyright © 2022 Organ Transplantation. All rights reserved.

Research highlights of renal transplantation in 2020: voice from China

Renal transplantation is the optimal approach to improve the quality of life and restore normal life for patients with end-stage renal diseases. With the development of medical techniques and immunosuppressants, the short-term survival of renal graft has been significantly prolonged, whereas the long-term survival remains to be urgently solved. Renal ischemia-reperfusion injury (IRI), acute rejection, chronic renal allograft dysfunction, renal fibrosis and other factors are still the major problems affecting the survival of renal graft. Relevant researches have always been hot spots in the field of renal transplantation. Meantime, 2020 is an extraordinary year. The novel coronavirus pneumonia (COVID-19) pandemic severely affects the development of all walks of life. Researches related to renal transplantation have also sprung up. In this article, the frontier hotspots of clinical and basic studies related to renal transplantation and the COVID-19 related researches in the field of renal transplantation in China were reviewed, aiming to provide novel therapeutic ideas and strategies.Copyright © 2021 Journal of Zhongshan University. All Rights Reserved.

Effect of the UNOS policy change on rates of rejection, infection and hospital readmission following heart transplantation.

BACKGROUND: The 2018 adult heart allocation policy sought to improve waitlist risk stratification, reduce waitlist mortality and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Post-transplant complications are significantly higher in patients on tMCS before transplantation, and early post-transplant complications impact long-term mortality. We sought to determine if policy change affected early post-transplant complication rates of rejection, infection and hospitalization. METHODS: We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between 11/1/2016 to 10/31/2017 and post-policy (POST) between 11/1/2018 to 10/31/2019. We used a multivariable logistic regression analysis to assess the effect of policy change on post-transplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis. RESULTS: The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p=0.8), hospitalization (p=0.69), and hospitalization due to rejection (p=0.76) and infection (p=0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p=0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras. CONCLUSION: The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early post-transplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term post-transplant mortality.

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.

TCR Alpha Beta and CD19+ Depleted Haploidentical Peripheral Stem Cell Transplantation Using Reduced Toxicity Conditioning Regimen with Pharmacokinetics Guided Busulfan, Fludarabine, Thiotepa and Thymoglobulin Offers Durable Donor Engraftment in Children with Primary Immune Deficiency Disorders

Background: Allogeneic hematopoietic cell transplantation (HCT) with ex vivo T cell receptor (TCR) alphabeta+ T cell and CD19+ B cell depletion is an effective approach for children with primary immune deficiency disorders (PIDD) as it combines advantages of high CD34+ cell dose facilitating rapid engraftment with low risk of Graft Versus Host Disease (GVHD). The ideal pre-conditioning regimen that facilitates robust donor engraftment without increasing risk of transplant related mortality has not been well defined with this approach. Method(s): We report the outcomes of 4 pediatric subjects: Chronic Granulomatous Disease (CGD) (2), Wiskott Aldrich Syndrome (WAS) (1), and RAC2 deficient Severe Combined Immunodeficiency (1) who underwent haploidentical HCT with TCRalphabeta+ T cell/CD19+ depletion at Johns Hopkins All Children's Hospital/Moffitt Cancer Center from 2020-2022 (NCT04414046). Pre-conditioning regimen consisted of distal thymoglobulin (7.5 mg/kg), fludarabine (175 mg/m2), thiotepa (10 mg/kg) and pharmacokinetic guided busulfan targeting a cumulative area under curve (cAUC) (65-75 mgxhr/L). Rituximab (200 mg/m2) was administered on day +1. Result(s): The median age at HCT was 51 months (range 10-163 months). All patients received mobilized peripheral blood stem cells from HLA- haploidentical donors (paternal=1, maternal=1 sibling=2). Median busulfan cAUC for all patients was 69 mgxhr/L (range 65-76). Median CD34 and TCR alphabeta T cell dose was 9.13x106 cells/kg (range 7.0-18.9x106) and 0.7x105 cells/kg (range 0.09-1.0x105). Median times to neutrophil and platelet engraftment were 11 days (9-12) and 11 days (range 8-15), respectively. All 4 patients are alive with median follow-up of 19.5 months (range 7-24). One patient developed late VOD without organ dysfunction that resolved with defibrotide. At last follow up, peripheral T and myeloid chimerisms exceeded 90% in all 4 patients. Average time to CD4 recovery (> 200x106/L) was 142 days. Pre-existing inflammatory bowel disease in CGD (n=1) and WAS (n=1) patients resolved immediately following transplant. There was no graft failure, and none developed Grade III-IV acute or extensive chronic GVHD. Patient with WAS developed recurrent autoimmune cytopenias requiring corticosteroids, rituximab, sirolimus and daratumumab, and ultimately resolved. Viral reactivations included EBV (n= 1), adeno (n= 1), HHV6 (n= 2), BK (n=1), norovirus (n=1), and late HSV (n=1), all responded to antivirals without disease. All patients acquired SARS-Cov-2 after transplant and recovered without sequelae. Conclusion(s): TCR alphabeta+ and CD19+ depleted haploidentical transplantation using a reduced toxicity conditioning regimen with pharmacokinetic guided busulfan, fludarabine, thiotepa and thymoglobulin is well-tolerated in young children with PIDD that results in rapid, durable engraftment with low likelihood of GVHD and graft rejection.Copyright © 2023 American Society for Transplantation and Cellular Therapy

COVID-19 vaccine causes of acceptance and rejection among university students in Baghdad

Despite numerous recommendations concerning individual and social preventive measures, including quarantine, wearing a mask, physical distancing, and handwashing, vaccination with effective and safe vaccines is still the most effective measure to break the chain of coronavirus SARS-Co2 transmission;still, vaccine hesitancy is a significant barrier to achieve high vaccination coverage against infectious diseases. An observational cross-sectional study was conducted among students of different universities (medical and non-medical) in Baghdad city Iraq using an online structured google form questionnaire from October 20 to November 20, 2021, and a final number of 658 students were included in the study. Causes of acceptance and rejection of the coronavirus vaccine were tested through the questionnaire. Of the total 658 participants, 557(84.7%) had received the vaccine before the start of the study and only 101 (15.3%) were not vaccinated;of them, more than half, 58(57.4%) were willing to, and the remaining 43(42.6%) refused to receive COVID-19 vaccination. Accordingly, the acceptance rate of the vaccine among the total participants was 93.5%, and the rejection rate was only 6.5%. The most chosen cause of vaccine acceptance was that they believed the vaccine protected them, their families and the community against COVID-19 infection and its complications with 63.5%. The most chosen rejection cause was fear of side effects of the vaccine, with 62% of the rejecting participants, followed by 28% having doubts about the vaccine's efficiency in protecting against COVID-19 infection. In this study, although the majority of the participants were willing to be vaccinated, still around one-third of them were under pressure from the government obligations and did not accept the vaccine due to their own convictions;education programs should be designed and directed to remove barriers to negative vaccine beliefs and perception to increase the vaccine coverage in the community. © 2022 by the authors.

Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.

BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

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

High prevalence of asymptomatic SARS-CoV-2 infection in a cohort of liver transplant recipients in central Italy

Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.Copyright © 2021 The Authors

Patterns And Outcomes Of Covid Positive Donor Utilization For Heart Transplant

Background: The outcomes following COVID positive donor utilization for heart transplant are unknown. Method(s): UNOS database was analyzed for heart transplants performed after the declaration of COVID pandemic on 11th March 2020 until 31st December 2021. The cohort was divided into two groups based on donor COVID antigen and NAAT results. Result(s): Since the onset of pandemic, there were 6855 heart transplants reported. COVID antigen or NAAT results were available in 5529 donors at the time of donation, of which 38 (0.7%) were positive. COVID positive donors (CPD) were accepted for older recipients (age 54 vs 48, p=0.04). Listing status 1 and 2 were similar in both groups (9% vs 5% and 24% vs 23% respectively). Durable mechanical support (LVAD, RVAD, TAH) were similar in both groups pre-transplant (31% vs 33%, p=0.3). There was no difference in days on waitlist (183 vs 176 days, p=0.9). Both groups had similar travel distance (261 vs 239 nautical miles, p=0.4) and ischemic time (3.6 vs 3.5 hours, p= 0.8). Simultaneous renal transplant rates were similar (10% vs 9%, p=0.8). CPD utilization increased with time (figure 1A) and was uniform across most UNOS regions (figure 1B) Post-transplant, there was no difference in length of stay (24 days in both groups) and acute rejection episode prior to discharge (4% vs 8%, p=0.6) or within one year (3% vs 4%). There were no deaths reported in the CPD group during a mean 72 days of follow up (range 0-365 days) (figure 2). Known hospitalization for rejection management were similar (3% vs 4%) post-transplant. Conclusion(s): Active COVID infection in donors did not affect survival or rejection rates in the short-term post-heart transplantCopyright © 2022

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Inferior Liver Transplant Outcomes during early COVID-19 pandemic in United States

Background:: Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Method(s):: We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Result(s):: Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01;92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusion(s):: During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.Copyright © 2022 The Author(s)