Association Between Severe SARS-CoV-2 Infection and De Novo HLA Donor Specific Antibody Production in Lung Transplant Recipients: Single-center study

Objectives: The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR. Method(s): We performed a retrospective chart review of 80 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 liters of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 liters of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. Result(s): A total of 23, 47, and 10 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSAwere detected in 0/23 (0%), 3/47 (6.3%), and 4/10 (40%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.0007) within 6 months post-COVID-19 diagnosis. Conclusion(s): Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.Copyright © 2023 Elsevier Inc.

COVID-19 Incidence and its Clinical Course in Liver Transplant Recipients.

Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.

SeroNet Pooling Project of immunocompromised populations

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.

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.

Development and prospect of clinical research on lung transplantation in post-COVID-19 era

Lung transplantation has been advanced for nearly half a century around the globe, and it has been developed rapidly for over 20 years in China. The field of lung transplantation in China has been gradually integrated into the international community. The outbreak of novel coronavirus pneumonia (COVID-19) in 2020 brought big challenges, as well as diverted the worldwide attention to the development of lung transplantation in China, accelerating international communication and cooperation. With the steadily deepening of clinical and basic research on lung transplantation for severe cases of COVID-19, organ transplant physicians have deepened the understanding and thinking of the maintenance of donors, selection of elderly and pediatric candidates, and perioperative management of recipients, as the future perspective of lung transplantation in China. For interdisciplinary research related to lung transplantation, it is necessary to carry out multi-center clinical trials with qualified study design and constantly promote the theoretic and practical innovation.Copyright © 2021 The authors.

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.

Systematic Review of the Clinical Effectiveness of Tixagevimab/Cilgavimab for Prophylaxis of Covid-19 in Immunocompromised Patients

Background/Aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination, and are at a high risk of SARSPOSTERS CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a combination of two monoclonal antibodies which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. Tixagevimab/Cilgavimab has been approved as COVID-19 prophylaxis for immunocompromised individuals, and is being used in over 32 different countries. The phase III PROVENT clinical trial found that high-risk participants prophylactically administered Tixagevimab/Cilgavimab had a significantly reduced risk of COVID- 19 infection after three and six months compared to controls. However, the PROVENT trial was conducted prior to the SARS-CoV- 2 Omicron wave, and did not include participants who had been previously vaccinated or infected. This systematic review provides an updated summary of the real-world clinical evidence of the efficacy of Tixagevimab/Cilgavimab for immunocompromised patients. The review reports breakthrough COVID-19 infections as its primary outcome. COVID-19-related hospitalisations, ITU admissions and mortality were included as secondary outcomes. Methods Two independent reviewers conducted electronic searches of PubMed and Medxriv, on 03/08/22 and 01/10/22. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. Odds ratios and 95% confidence intervals (CI) between intervention and control groups were also calculated. The GRADE tool was used to assess the level of certainty for the primary outcome. Results 17 clinical studies were included in the review, with a total of 24,773 immunocompromised participants from across the world, of whom 10,775 received Tixagevimab/Cilgavimab. One randomised controlled trial, ten retrospective cohort studies (two of which were preprints) and six prospective cohort studies (one preprint) were included. The majority of studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Reasons for participant immunocompromise included rheumatology patients treated with immunosuppressant drugs, transplant recipients and those with malignancies. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID- 19 breakthrough infection was 40.47% (CI 29.82-49.67;p<0.0001), COVID-19 hospitalisation- 69.23% (CI: 50.78-81.64;p<0.00001), ITU admission- 87.89% (CI: 47.12-98.66;p=0.0008), all-cause mortality- 81.29% (66.93-90.28;p<0.0001 and COVID-19-specifc mortality- 86.36% (CI:-6.21-99.70;p=0.0351). Conclusion There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised groups, notably demonstrating effectiveness during the Omicron wave. This systematic review demonstrates the significant clinical effectiveness of prophylactic Tixagevimb/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is critically important that largerscale and better-controlled studies are performed to highlight the significant clinical benefit of prophylactic antibody treatment in immunocompromised groups.

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.

Hospitalisation and death in lung transplant recipients following COVID-19 infection

Introduction/Aim: Rates of hospitalisation and death from COVID-19 in lung transplant (LTx) recipients vary internationally. We aimed to assess risk factors for this in an Australian cohort. Method(s): We performed a retrospective cohort study of all LTx recipients between January 2020 and September 2022. LTx recipients with COVID-19 were included. Baseline characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. Result(s): 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves with 40(31.3%) requiring hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77). The cohort was of Caucasian ethnicity 105 (82%), 48% were female with high vaccination rates (98.4%). Chronic lung allograft dysfunction (CLAD) was present in 48 (37.5%). 103 (80.5%) of patients received early SARS-CoV-2 treatment with either Sotrovimab 84(65%), Molnupirivir 50(39%) or combination 31(24%). 25 patients (19.5%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed that recipient age (1-unit change OR 1.04 95% CI 1.01-1.07 p = 0.019) was associated with an increased risk, whereas Molnupiravir was protective (OR 0.32 95% CI 0.13-0.80 p = 0.02). In univariable analysis, increasing age (1-unit change, OR 1.07 95% CI 1.02-1.129 p = 0.01) and severe disease (OR 9.95 95% CI 2.58-38.32 p =< 0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Conclusion(s): Recipient age is a significant risk factor for both hospitalisation and death, and older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with emerging therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia.

Real World Experience Using Tixagevimab/Cilgavimab (EvusheldTM) in Pre-Exposure Prophylaxis for Allogeneic Hematopoietic Cell Transplant Recipients: A Single Center Retrospective Review

Background: Tixagevimab(Txg)/cilgavimab (Cgv) was given emergency use authorization (EUA) to provide passive immunity against COVID-19(CoV) for immunocompromised (IC) pts who may not mount an adequate response to CoV vaccination [1]. Recipients of allogeneic hematopoietic cell transplant (Allo-HCT) are amongst the most IC. Due to high risk of mortality and complications of CoV in this population, Txg/ Cgv was used as pre-exposure prophylaxis (PrEP) under EUA without prior study. Our study aims to assess efficacy and adverse events (AE) of Txg/Cgv administration in this cohort of patients to help guide future practice. Method(s): We retrospectively investigated Allo-HCT recipients who received Txg/Cgv as PrEP. Data were gathered including changes in blood counts, incidence of graft-vs-host-disease (GVHD), history of prior CoV infection and vaccination status. Pts who developed CoV infection after PrEP were assessed for supplemental oxygen(O2) need and hospitalization. Data cutoff date was 9/30/2022. Result(s): A total of 18 Allo-HCT recipients received Txg/Cgv. Table 1 summarizes patient and transplant characteristics. Thirteen (72.2%) pts received 2 doses of 150mg of Txg / Cgv, while 4 pts received 1 dose of 300mg, and one patient received one dose of 150mg. Median time to first dose was 213 days [range 22-3660] post-transplant. Two pts had lab confirmed CoV, one at 24 days post dosing and the 2nd patient at 22 days post dose. Neither required supplemental O2;one was hospitalized for fever. Prior to dosing, 44.4% (8/18) of pts had GVHD. (Table Presented) (Figure Presented) (Figure Presented) Of these, 62.5% (5/8) had no changes in the severity of their GVHD. Two of 8 (25%) pts with pre-existing chronic GVHD had a flare of symptoms. Two (25%) had improvement of GVHD. Two pts developed new onset acute GVHD following Txg/Cgv administration, one requiring 1mg/kg prednisone and the other topical steroids (2/18, 11%). Figure 1 summarizes GVHD patterns observed. Hematologic parameters did not change significantly, see Figure 2. None of the pts reported any subjective AE following dosing. Summary: Txg/Cgv was found to be safe and effective for Allo-HCT pts, without significant toxicity. Two patients had new onset GVHD and 2 patients had progressive GVHD. Whether there is a true association between Txg/Cgv and development of GVHD should be investigated in a larger cohort and then investigated for possible underlying mechanisms.Copyright © 2023 American Society for Transplantation and Cellular Therapy

SARS-CoV-2 INFECTIONS AMONG 275 PATIENTS WITH TIXAGEVIMAB/ CILGAVIMAB PROPHYLAXIS

Background: At the end of 2021, concomitantly with the beginning of Omicron variant circulation, pre-exposure prophylaxis with the dual monoclonal long-acting monoclonal antibodies tixagevimab/cilgavimab became available in France to protect patients non-responding or non-eligible to SARS-CoV-2 vaccination at risk of severe COVID-19. Method(s): This study included patients who received tixagevimab/cilgavimab for pre-exposure prophylaxis independently of vaccination status or previous SARS-CoV-2 infection. This prophylaxis strategy was implemented at the Bichat-Claude Bernard University Hospital, Paris since December 2021 Last date of follow-up was November 1st, 2022. Incident SARS-CoV-2 infections were detected based on positive RT-PCR result and/or anti-nucleocapsid antibodies seroconversion. Severe COVID-19 was defined as an infection leading to an hospitalization requiring oxygenotherapy and/or high dose corticotherapy. Result(s): Among the 275 patients who received a tixagevimab/cilgavimab preexposure prophylaxis, 55% (n=153) were solid organ transplant recipients (50% lung, 46% kidney, 4% heart transplants), 42% (n=116) had an autoimmune disease, and 3% (n=6) had other indications. 51% (n=141) of all patients received rituximab. No severe adverse event of tixagevimab/cilgavimab was observed. Incident SARS-CoV-2 infection was diagnosed in 67 patients (24%). Among them, 59% (n=40) were solid organ transplant recipients, 36% (n=24) had an autoimmune disease and overall 52% had received rituximab. For the 56 patients whose infection date was available, the median delay between the last infusion of tixagevimab/cilgavimab and SARS-CoV-2 infection was 62 days (IQR=[30-97]). During the study period, 57% of incident infections occurred between December 17th, 2021 and May 31st, 2022, when BA.1 and BA.2 were the major Omicron sublineages in France, and 43% between June 1st, 2022 and November 2022 1st, a period during which BA.4 and BA.5 were predominant in France. Severe COVID-19 occurred in 6 patients out of 67 (9%);5 were solid organ transplant recipients and 3 received rituximab. No death due to COVID-19 was reported. Conclusion(s): Overall, 76% of patients receiving pre-exposure prophylaxis with tixagevimab/cilgavimab had no incident SARS-CoV-2 infection during the study period. Severe COVID-19 was observed in 9% of infected patients. These results suggest a potential protective effect in-vivo of tixagevimab/cilgavimab during the study period despite the circulation of different Omicron sublineages.

Sotrovimab Pharmacokinetics and Covariate Effects in Hematopoietic Stem Cell Transplant Recipients

Hematopoietic cell transplant (HCT) recipients are at increased risk of morbidity and mortality from COVID-19. They may have lower SARS-CoV-2-directed antibody levels due to protein loss from the gastrointestinal (GI) tract as a result of preparative regimen-related toxicity and graft-vs.-host disease (GVHD). In fact, previous studies suggested that GI GVHD or diarrhea from other etiologies were associated with a reduction in the half-life of monoclonal antibodies (mAbs). Hence, understanding the pharmacokinetic (PK) profile of mAbs targeting SARS-CoV-2 in this vulnerable population is critical for dose-selection and predicting the duration of protection against COVID-19. This analysis aims to use a population pharmacokinetics (popPK) approach to evaluate the PK of sotrovimab and the effect of covariates in HCT recipients. In a Phase I trial (COVIDMAB), all participants received 500 mg sotrovimab IV prophylactically within one week prior to starting transplant conditioning. Sotrovimab serum concentrations were determined weekly for up to 12 weeks in autologous (n=5) and allogeneic (n=15) HCT recipients (129 observations). Sotrovimb PK and the effect of covariates were analyzed using popPK modeling in NONMEM (version 7.4). GVHD and diarrhea severity data were collected weekly via survey and included as time-dependent covariates during the covariate screening process. The final PK model with covariates was validated using simulation-based validation and goodness of fit plots. PK data were compared to non-transplant patients from 1891 patients with COVID-19 in COMET-ICE, COMET-PEAK, BLAZE-4, and COMET-TAIL and 38 healthy individuals enrolled in GlaxoSmithKline Pharma Study 217653. A two-compartment model best described sotrovimab PK in HCT recipients. In comparison to non-transplant patients, sotrovimab clearance (CL) was 14.0% higher in HCT recipients. Weight was a significant covariate on sotrovimab CL and (Figure Presented) volume of distribution in the central compartment (V2). With every 10 kg increase in body weight, sotrovimab CL and V2 were estimated to increase by 9.5% and 5.5%, respectively. Diarrhea severity was also a significant covariate on sotrovimab CL. HCT recipients with grade 3 diarrhea showed an increase in CL by 1.5-fold compared to those without diarrhea. Based on popPK analyses, sotrovimab CL was higher in HCT recipients compared to non-transplant patients. Higher bodyweight as well as diarrhea resulted in increased sotrovimab CL. There were only 3 patients with GI GVHD, and larger studies are needed to determine whether diarrhea due to GI GVHD or conditioning toxicity was responsible for the observed increase in sotrovimab CL. Further validation of these findings in a larger number of HCT recipients is also warranted to help optimize mAb dosing for COVID-19 prophylaxis and determine whether presence of large-volume diarrhea may require intensified dosing strategiesCopyright © 2023 American Society for Transplantation and Cellular Therapy

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.

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

Partial recovery of SARS-CoV-2 immunity after booster vaccination in renal transplant recipients

The pandemic caused by the SARS-CoV-2 coronavirus has been especially detrimental to patients with end-stage renal disease. History with other vaccines suggests that patients with renal disease may not respond adequately to the SARS-CoV-2 vaccine. The aim of this study is to evaluate the immunity to SARS-CoV-2 mRNA vaccines in renal patients. Post SARS-CoV-2 vaccination first, and after the booster dose, antibodies and cellular immunity were studied in patients on hemodialysis (N = 20), peritoneal dialysis (N = 10) and renal transplantation (N = 10). After the two doses of vaccine, there was an effective immunity in dialysis patients, with 100% seroconversion and 87% detection of cellular immunity (85% in hemodialysis and 90% in peritoneal dialysis). In contrast, in renal transplant recipients there was only 50% seroconversion and cellular immunity was detected in 30% of patients. After the booster dose, all dialysis patients achieved a cellular and antibody immunity, whereas in transplant patients, despite improvement, 20% did not produce antibodies and in 37.5% cellular immunity could not be detected. The mRNA vaccine plus booster performs excellently in dialysis patients, whereas in kidney transplant recipients, despite the booster, complete immunization is not achieved.Copyright © 2022

COVID-19 in liver transplant recipients

Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients;(2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.Copyright © 2021 The Authors

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)

Repeated COVID-19 infection in recipients of post-living donor liver transplantation: Two real-life cases

COVID-19 is an emerging pandemic. The course and management of the disease in the liver transplant setting may be difficult due to a long-standing immunosuppressive state. In Egypt, the only available option is living donor liver transplantation (LDLT). In our centre, we have transplanted 440 livers since 2008. In this study, we report a single-centre experience with COVID-19 infection in long-term liver transplant recipients. A total of 25 recipients (5.7 %) had COVID-19 infections since March 2020. Among these recipients, two developed COVID-19 infections twice, approximately three and two months apart, respectively.Copyright © 2021 The Author(s)

Impact of COVID-19 on 2020 transplant activity and waiting lists in France

The COVID-19 pandemic strongly affected organ procurement and transplantation in France, despite the intense efforts of all participants in this domain. In 2020, the identification and procurement of deceased donors fell by 12% and 21% respectively, compared with the mean of the preceding 2 years. Similarly, the number of new registrations on the national waiting list declined by 12% and the number of transplants by 24%. The 3-month cumulative incidence of death or drop out for worsening condition of patients awaiting a liver transplant was significantly greater in 2020 compared to the previous 2 years. Continuous monitoring at the national level of early post-transplant outcomes showed no deterioration for any organ in 2020. At the end of 2020, less than 1% of transplant candidates and less than 1% of graft recipients - of any organ - had died of COVID-19.Copyright © 2021 The Author(s)