SARS-CoV-2 infection and solid organ transplantation.

Transplantation has become a valid therapeutic option for an increasing number of patients with end-stage organ disease. The emergence of SARS-CoV-2 coronavirus infection and associated disease (COVID-19) has alarmed the transplant community, since recommendations for adequate follow-up of organ transplant recipients during the acute phase of a pandemic are limited. Furthermore, treatment options against COVID-19 disease and adequate adjustment of immunosuppression in at risk patients remain a concern. This review summarizes current knowledge on the incidence and clinical course of SARS-CoV-2 infection in patients with solid organ transplantation. It also discusses therapeutic strategies and provides general recommendations on how to proceed with transplantation programs in a time when health care resources may become scarce.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients.

BACKGROUND: Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness. METHODS: Comparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation. RESULTS: Ionophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (< 0.01%) when tested 2 weeks after vaccination or later, but were detectable after in vitro culture of PBMCs with mRNA-1273 vaccine to enrich memory T cell responses. This was also seen in COVID-19-recovered lung transplantation recipients. Comparison of their enriched memory responses to controls revealed relatively similar CD4+ T cell memory, but markedly reduced CD8+ T cell memory both after primary vaccination or a booster dose. These responses were not correlated to age or time after transplantation. The vaccine-induced CD4+ and CD8+ responses correlated well in the healthy control group, but poorly in the transplantation groups. CONCLUSIONS: These results reveal a specific defect in CD8+ T cells, which have key roles both in transplanted organ rejection but also antiviral effector responses. Overcoming this defect will require strategies to enhance vaccine immunogenicity in immunocompromised persons.

Absence of detectable SARS-CoV-2 replication in ex vivo cultured cornea and cornea-derived epithelial cells.

PURPOSE: To study the possibility of SARS-CoV-2 to infect human corneal cells and tissues under standard corneal culture conditions using explants of COVID-19 donors and primary cornea-derived epithelial cells. METHODS: Cornea isolated from deceased COVID-19 donors was cultured for 4 weeks, and SARS-CoV-2 replication was monitored by qRT-PCR. Furthermore, primary corneal epithelial cells from healthy donors were cultured ex vivo and infected with SARS-CoV-2 and human cytomegalovirus (HCMV) as a control. Infection status was assessed by western blotting and reporter gene expression using green fluorescent protein-expressing viral strains. ACE2 and TMPRSS2 receptor expression levels in cornea and epithelial cells were assessed by qRT-PCR. RESULTS: We did not detect SARS-CoV-2 replication in 10 corneas isolated from deceased COVID-19 patients and cultured for 4 weeks, indicating absence of infection under natural conditions. Furthermore, high-titer SARS-CoV-2 infection of ex vivo cultured cornea-derived epithelial cells did not result in productive virus replication. In contrast, the same cells were highly permissive for HCMV. This phenotype could potentially be explained by low ACE2 and TMPRSS2 transcriptional activity in cornea and cornea-derived epithelial cells. CONCLUSIONS: Our data suggest that cornea and limbal epithelial cells are refractory to productive SARS-CoV-2 infection. This could be due to the absence of robust receptor expression levels necessary for viral entry. This study adds further evidence to support the very low possibility of transmission of SARS-CoV-2 from an infected corneal transplant donor to a recipient in corneal organ cultures.

Organ transplantation and vaccination

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.Copyright © 2022 Journal of Zhongshan University. All Rights Reserved.

Changes in Disease Etiology of Deceased Donor Liver Transplantations Following Acuity Circles Policy Implementation

Introduction: The Acuity Circles (AC) allocation policy was implemented on February 4, 2020, with the primary intent of reducing disparities in access to deceased donor liver transplants (DDLTs). Overall, it has been successful at achieving this goal. However, changes in end-stage liver disease etiology following the policy change have not been well-characterized. Our goal was to understand how primary etiology of disease in DDLTs has changed since implementation of AC. Method(s): Data from the Organ Procurement Transplantation Network (OPTN) and United Network of Organ Sharing (UNOS) were analyzed to compare the primary classified etiologies of liver disease for DDLTs overall and based on allocation Model-for-end-stage-liver-disease (aMELD) categories used for AC sharing: aMELD>=37, aMELD 33-36, aMELD 29-32, aMELD 15-28, and aMELD<=14 DDLTs. Time was divided into four equivalent "eras" of 256 days duration by date of transplantation: 1) 9/10/18-5/23/19 (Era 1);2) 5/24/19-2/3/20 (Era 2);3) 2/4/20-10/16/20 (Era 3);and 4) 10/17/20-6/29/21 (Era 4). Result(s): The percentage of all DDLTs for alcohol-related liver disease (ARLD) increased from 32.3% pre-AC to 38.7% of DDLTs post AC. This was met with a corresponding decrease in the relative percentage of DDLTs related to Hepatitis C Virus (from 17.0% of DDLTs pre-AC to 12.2% post-AC), with the relative differences of other etiologies being a less than 1% difference pre- vs post- AC. There is a consistent increase in the share of DDLTs due to ARLD across each Era. The rise in adult DDLTs for ARLD was most pronounced among aMELD >=37 recipients, although similar trends were seen among aMELD 33-36 and aMELD 29-32 groups, but not aMELD 15-28 and aMELD <=14 groups. The median age of adult DDLTs for ARLD decreased consistently over time for the aMELD >=37 group, but not for the aMELD 33-36 and aMELD 29-32 groups. (Figure) (Table) Conclusion(s): Following implementation of AC, there was a relative increase in DDLTs due to ARLD. The younger age and high aMELD scores of these patients suggests these may be largely among patients with acute alcoholic hepatitis. This would align with published data on the overall increase in liver transplantation due to ARLD during the COVID-19 pandemic. (Figure Presented).

Application prospects of organoids in organ transplantation

In recent years, organoid technology has become one of the major technological breakthroughs in biomedical field. As miniature organs constructed by three-dimensional culture of tissue stem cells in vitro, organoids are highly consistent with the source tissues in terms of tissue structures, cell types and functions, which serve as an ideal model for biomedical basic research, drug research and development and clinical precision medicine, and show important potential value in regenerative medicine. Organ transplantation is one of the most effective approaches to treat organ failure. However, the source of donor organs is currently limited, which could not meet the patients' needs. Identifying suitable graft substitutes is the key to breaking through the predicament. Organoids could be derived from the autologous tissues of patients. Multiple studies have demonstrated that organoids possess potent transplantation and repairing capabilities and may effectively avert the risk of immune rejection and tumorigenicity, etc. In this article, the development process and main application directions of organoid technology were summarized, and the application prospect and challenges of organoids in organ transplantation were reviewed and predicted.Copyright © 2022 Journal of Zhongshan University. All right reserved.

Overview of global organ donation and transplantation in 2020

Objective At present, the novel coronavirus pneumonia (COVID-19) pandemic is still raging in certain regions around the globe, and the prevention and control of the pandemic should be strengthened. Under the challenges of respective social environment and allocation of medical resources, and support from the inertia and inherent productivity of the system on which the industry depends, extensive attempts are being delivered to push forward the work of organ donation and transplantation in each country. Under the guidance of national experts and committee members, Shanxi Provincial Human Organ Procurement and Allocation Service Center was established on August 28, 2018 approved by the former Shanxi Provincial Health and Family Planning Commission. It is the only independent non-profit medical institution in Shanxi Province. In this article, the system construction of citizen's organ donation and transplantation fitting national and provincial conditions was further explored according to the data analysis of organ donation and transplantation in the United States and Spain during the COVID-19 pandemic combined with the implementation of organ donation work in Shanxi Provincial Human Organ Procurement and Allocation Service Center.Copyright © 2021 The authors.

Study on job satisfaction of human organ donation coordinators in Fujian province during the normalization period of epidemic prevention and control

Objective To analyze the status of job satisfaction of human organ donation coordinators in Fujian province during the normalization period of novel coronavirus pneumonia (COVID-19) epidemic prevention and control and put forward corresponding suggestions. Methods The job satisfaction of human organ donation coordinators in Fujian province was investigated by online questionnaires. The correlation analysis of all dimensions of the overall job satisfaction of human organ donation coordinators was carried out, and the influencing factors of the overall job satisfaction were analyzed. Results The overall job satisfaction of human organ donation coordinators was (2.9 0.8), which was a relatively low score. The job promotion satisfaction was (4.7 1.3), (2.0 1.4) for the job pay and benefits satisfaction, and (2.0 1.3) for the job communication satisfaction. The job pay and benefits satisfaction was positively correlated with job communication satisfaction -0.653 , P<0.05). Multiple factors differed in job satisfaction. The overall job satisfaction of human organ donation coordinators was associated with gender, nature of job, working years, average monthly income, age, educational background and nature of post. Conclusions The job satisfaction of human organ donation coordinators is relatively low in Fujian province during the normalization period of COVID-19 epidemic prevention and control. Flexible and diverse methods should be employed from the government and hospital levels to further improve security policies for human organ donation coordinators.Copyright © 2021 Journal of Zhongshan University. All right reserved.

Pancreatitis Secondary to Paxlovid-Induced Tacrolimus Toxicity

Introduction: Pancreatitis is a very common gastrointestinal disease that results in hospital admission. Early detection and treatment leads to better outcomes. This is the first reported case of pancreatitis secondary to elevated tacrolimus in a patient with prior renal transplantation after receiving Paxlovid for a COVID-19 infection. Case Description/Methods: A 57-year-old male with past medical history of 4 renal transplants secondary to posterior urethral valves who presented to the emergency room with acute onset epigastric pain for 24 hours. He was on tacrolimus 5 mg every 48 hours monotherapy for his immunosuppression. 10 days prior to his presentation he had developed chills and anxiety. He tested positive for COVID-19 at that time on a home rapid test. His symptoms had not significantly improved and given his immunosuppressed state he was given Paxlovid (Nirmatrelvir/ritonavir). He took 2 days of Paxlovid, however after his second day of treatment he developed severe epigastric pain requiring him to go to the emergency room. On admission his labs were notable for a lipase of 150 U/L (ULN 63 U/L). He underwent a CT scan was notable for an enlarged pancreatic head and neck with peripancreatic fat stranding (Figure). He also had a right upper quadrant ultrasound without any cholelithiasis and only trace sludge noted. His creatinine was noted to be 1.81 mg/dl which was above his baseline of 1.2 mg/dl. His tacrolimus trough level resulted at a level 45.6 ng/ml and later peaked at 82.2 ng/ml. His liver enzymes were normal. He was treated as acute pancreatitis with hydration and his tacrolimus was held with overall clinical improvement. Discussion(s): Tacrolimus is one of the most common medications used in solid organ transplantation. It is a calcineurin inhibitor that inhibits both T-lymphocyte signal transduction and IL-2 transcription. It is metabolized by the protein CYP3A and levels are monitored closely. Paxlovid is currently prescribed as an antiviral therapy for COVID-19 infection. The ritonavir compound in Paxlovid is potent inhibitor of CYP3A. Currently the guidelines do not recommend Paxlvoid as a therapeutic in patients taking tacrolimus as there is concern about increased drug levels. There have been several case reports of pancreatitis in setting of tacrolimus. This case report helps to demonstrate the need for close monitoring of therapeutics levels, especially in medications with high risk of drug to drug interaction to help prevent serious side effects such as tacrolimus induced pancreatitis.

Covid-19 Outcome in Patients with and without Cirrhosis

Background: Severe outcomes of COVID-19 are associated with advancing age, and multiple medical comorbidities. The impact of COVID-19 on the clinical course of patients with cirrhosis has not been well studied. We determined the effect of SARS-CoV-2 infection on the hospitalization and survival rates of patients with cirrhosis. Method(s): Using ICD-10-CM codes, we identified all Veterans with a diagnosis of cirrhosis in the VA Corporate Data Warehouse and COVID-19 Shared Data Resource. Study cohort included Veterans who were tested for SARS-CoV-2 and had no history of organ transplantation or malignancies. Each SARS-CoV-2 positive case was propensity-score matched by demographics and comorbidities with up to two SARS-CoV-2 negative controls. The primary endpoints were acute care hospitalization, admission to intensive care, respiratory support, or death. Result(s): Of 1,115,037 individuals tested for SARS-CoV-2, 31,680 were noted to have cirrhosis and among them 5,047 (16%) were SARS-CoV-2 positive. After exclusions and propensity-score matching, 5,047 SARS-CoV-2 positive and 9,913 propensity score matched SARS-CoV-2 negative individuals were included in the analysis cohort. Median age was 67 years, 95% were men and 25% were of black race. Median BMI was 30 and history of hypertension, diabetes, cardiovascular and chronic pulmonary disease was noted among 81%, 54%, 56% and 32% respectively. Among all cirrhotic individuals, SARS-CoV-2 positive individuals less frequently progressed to hepatic decompensation (3.1% vs 4.8%, P< 0.0001) or hospitalization (35.7% vs 38.2%, P=0.002), but more frequently required ICU admission 15% vs 12.2%, P< 0.0001) or respiratory support (7.3% vs 8.4%, P=0.01). Among those admitted, length of hospital stay was longer among SARS-CoV-2 positive individuals (7 vs 4 days, P< 0.0001). In Cox regression analysis, SARS-CoV-2 positivity was associated with a higher risk of all-cause mortality (HR 1.37, 95% CI 1.19,1.56). Conclusion(s): Although patients with cirrhosis and COVID-19 were less often hospitalized, they had longer duration of hospitalization and were at higher risk of severe or critical illness and death. (Figure Presented).

Prolonged Viable Viral Shedding in Immunocompromised Patients with Covid-19

Background: Immunocompromised patients with COVID-19 tend to shed viable virus for a prolonged period. Therefore, for moderately or severely immunocompromised patients with COVID-19, CDC recommends an isolation period of at least 20 days and ending isolation in conjunction with serial testing and consultation with an infectious disease specialist. However, data on viral kinetics and risk factors for prolonged viral shedding in these patients are limited. Method(s): From February 1, 2022 to April 1, 2022, we collected weekly saliva samples from immunocompromised patients with COVID-19 admitted to a tertiary hospital in Seoul, South Korea. Genomic and subgenomic RNAs were measured, and virus culture was performed. Result(s): A total of 41 patients were enrolled;29 (70%) were receiving chemotherapy against hematologic malignancies and the remaining 12 (30%) had undergone solid organ transplantation. Of the 41 patients, 14 (34%) had received 3 doses or more of COVID-19 vaccines. Real-time RT-PCR revealed that 7 (17%) were infected with Omicron BA.1, and 33 (80%) with Omicron BA.2. The median duration of viable virus shedding was 4 weeks (IQR 3-6). Patients undergoing B-cell depleting therapy shed viable virus for longer than the comparator (p=0.01). Multivariable analysis showed that 3-dose or more vaccination (HR 0.33, 95% CI 0.12 - 0.93, p = 0.04) and B-cell depleting therapy (HR 12.50, 95% CI 2.44 - 100.00, p = 0.003) independently affected viable virus shedding of SARS-CoV-2. Conclusion(s): Immunocompromised patients with COVID-19 shed viable virus for median 4 weeks. B-cell depleting therapy increases the risk of prolonged viable viral shedding, while completion of a primary vaccine series reduces this risk. Overall distribution of samples according to genomic viral copy number and culture positivity. Red dot indicates positive culture results, whereas blue dot indicated negative culture results. (Figure Presented).

Influencia de la pandemia por Covid 19 en el trasplante de órganos

En el mes de Diciembre (2019) se diagnosticó la infección viral que tuvo una rápida expansión. En el mes de Junio (2020) solo en 188 países fueron diagnosticados 35 millones de pacientes. Desgraciadamente en nuestro país los resultados de la atención a los enfermos (diagnostico, aislamiento, atención), fue peor que en otros muchos (Alemania, Italia, Corea, Taiwán, Grecia, Portugal, Francia, Japón y otros). 778 pacientes trasplantados sufrieron la infección, de ellos, 249 en la Comunidad de Madrid. La donación de órganos se redujo rápidamente debido a que las áreas de hospitalización, UCI, quirófanos, actividad hospitalaria en general hubo de dedicarse al tratamiento de los enfermos infectados. Hubo de asumir la reducción de trasplantes de riñón, hígado, corazón, pulmón, en casi el 90% de las cifras correspondientes a los dos años anteriores (en el mes de abril 0%), en el periodo marzo-Julio 2020. No se permitió el trasplante con donante vivo,” Split” o "Cluster”. Solo en la Comunidad de Madrid se realizaron 37 trasplantes menos en 2020 que en 2019. Los motivos de este descenso fue la reducción de camas en UCI, de posibilidades de utilización de quirófanos, menor número de facultativos, enfermeras, personal sanitario en general (861.112 infectados, de los cuales 36.000 eran sanitarios, con una mortalidad global de 36.000). Nuevos protocolos, formas de tratamiento, vacunación, hicieron posible volver a la cifra de trasplantes realizados entre 2018-2019.Alternate : On 31 December 2019 COVID-19 Viral infection was diagnoses. On june 2020 only in 188 countries 33 millons of infected people were detected. Unfortunately in Spain the results of the treatment has been worse than in Germany, Italy, Corea, Taiwan., Grece, Portugal, France, Japan, and others. 778 transplanted patients were infected. 249 of them in Madrid area. Organ donation was reduced. National Organization of Organ Trasplantation diminished donation, and transplantation of kidney, liver, heart, lung close to 90% (in april, 0%) from march to july 2020. Living rolated or split, and cluster trasplantation was not permited. In Madrid area, on 2020 were done 37 transplantation less than in 2019 the causes of that were the reduction of UCI beds, time in the OR, reduction of doctors and nurses. 861.112 infected people, 32.992 died and from the total number of patients, 36.000 were included as, doctors, nurses and other related with health care areas new protocols, hospitals, intensive care areas, etc were established along 2020 going back to the previous results obtained during 2018-2019.

Impact of Invasive Pulmonary Aspergillosis in Critically Ill Surgical Patients with or without Solid Organ Transplantation.

BACKGROUND: Critically ill patients, especially those who have undergone solid organ transplantation (SOT), are at risk of invasive pulmonary aspergillosis (IPA). The outcome relevance of adequately treated putative IPA (pIPA) is a matter of debate. The aim of this study is to assess the outcome relevance of pIPA in a cohort of critically ill patients with and without SOT. METHODS: Data from 121 surgical critically ill patients with pIPA (n = 30) or non-pIPA (n = 91) were included. Cox regression analysis was used to identify risk factors for mortality and unfavourable outcomes after 28 and 90 days. RESULTS: Mortality rates at 28 days were similar across the whole cohort of patients (pIPA: 31% vs. non-pIPA: 27%) and did not differ in the subgroup of patients after SOT (pIPA: 17% vs. non-pIPA: 22%). A higher Sequential Organ Failure Assessment (SOFA) score and evidence of bacteraemia were identified as risk factors for mortality and unfavourable outcome, whereas pIPA itself was not identified as an independent predictor for poor outcomes. CONCLUSIONS: Adequately treated pIPA did not increase the risk of death or an unfavourable outcome in this mixed cohort of critically ill patients with or without SOT, whereas higher disease severity and bacteraemia negatively affected the outcome.

Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort.

OBJECTIVES: The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. METHODS: Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t0), second dose (t1), 3 ± 1 month (t2), and 1 month after third dose (t3). Negative AbR at t3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort. RESULTS: Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t0 to t3. Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36-0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35-0.37]). DISCUSSION: Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms.

Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed. METHODS: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 - January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels. RESULTS: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age, and shorter time from transplant. CONCLUSIONS: SOT patients with non-high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI.

Adequacy of Sotrovimab Prescription in Sarscov- 2 Infection in a University Hospital

Background and Importance The Spanish Medicines and Health Products Agency (AEMPS) has developed criteria to adapt the prescription of sotrovimab1, due to the pandemic situation and the limited drug stock. Aim and Objectives To describe the patients' population on treatment with sotrovimab and to assess the adequacy of this prescription according to the criteria established by the AEMPS. Material and Methods Retrospective observational study analysing all sotrovimab prescriptions in patients with SARS-CoV-2 infection from 01/25/2022 to 08/31/2022. Demographic variables and data required by the AEMPS for sotrovimab prescription were collected: Omicron variant infection, SARS-CoV-2 vaccination status, serology [anti-S antibody< 260 BAU (binding antibody units)/mL]. Also, patients had to belong to one of the following groups: * Group 1: Immunocompromised, regardless of vaccination status. * Group 2: >80 years unvaccinated. * Group 3: >65 years (regardless of vaccination status) and >=1 risk factor for progression. Prescriptions for sotrovimab were collected and analysed to determine whether they met the criteria and whether they were accepted. Data collected from electronic medical records and processed using Excel2019. Results Fifty patients were included, 62% male;median age 69 years (IQR=60-76). 100% had the Omicron variant. Vaccination status: 84% complete, 6% incomplete and 10% unvaccinated. Serology: 96% (<260 BAU/mL) and 4% (>260 BAU/ ml). 92% belonged to group 1 (39% solid organ transplantation, 29% active myelotoxic chemotherapy, 13% non-cytotoxic onco-haematological treatments with neutropenia/lymphopenia, 13% treatment with biological immunomodulators, 2% Down's syndrome, 2% haematopoietic stem cell transplantation or CAR-T, 2% HIV infection (with <=200 cells/mL). Two per cent belonged to group 2. The remaining patients (6%) did not belong to any group. Ten per cent of the applications did not meet the criteria: four of them were not accepted (patients did not belong to any risk group);one was accepted, although it was a well-controlled HIV. Conclusion and Relevance The main profile of patients treated with sotrovimab is men with solid organ transplantation, vaccinated and with negative immunity to SARS-CoV-2. Although the appropriateness of the prescription is high, it is necessary to continue protocolising the use of this drug to ensure its rational use.

Solid organ graft-versus-host disease in a recipient of a COVID-19 positive liver graft

A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors

Coronavirus disease 2019 vaccination in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are a high-risk population for coronavirus disease 2019 (COVID-19), and the safety and efficacy of COVID-19 vaccines in this population is of great concern. At present, the published studies on COVID-19 vaccines for SOT recipients are mainly about mRNA vaccines and there are a few cases reports on recombinant adenovirus vector-based vaccines. These results show that the COVID-19 vaccines are safe for the SOT recipients, but the immune response rates are lower and the incidence of vaccine breakthrough infections is higher than that in the general population. Based on the results of the current studies, SOT recipients can start to be vaccinated with COVID-19 vaccines 1 to 3 months after organ transplantation. Prevention of COVID-19 after vaccination is still necessary to avoid vaccine breakthrough infections.Copyright © 2021 by the Chinese Medical Association.

The positive impact of the COVID 19 pandemic on organ utilisation in liver transplantation

Background: As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ''organ utilisation'' in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years. Method(s): Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported. Result(s): The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638;55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%. Conclusion(s): The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.Copyright © 2022