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American Journal of Transplantation: Volume 21, Number 8, August 2021
doi : 10.1111/ajt.16042
Volume 21, Issue 8
On the cover: The COVID-19 pandemic has poignantly reminded the entire transplantation community, patients and physicians, about the downsides of chronic lifelong immunosuppression that are often forgotten in daily life and practice, respectively. At the outset, concerns centered on the potential for immunosuppressed compared to non immunosuppressed patients to experience heightened morbidity and mortality from SARS-CoV-2 infection. Now, more than a year and a half later, concerns have pivoted to reduced COVID vaccine immunogenicity that may translate into reduced vaccine efficacy. Multiple articles in this issue highlight the clinical and immunological impact of COVID-19 in multiple solid organ transplant cohorts (kidney, liver, heart, and lung), including children as well as the humoral and cellular responses to SARS-CoV-2 mRNA vaccines. The theme is extended by two additional articles: one that examines antibody responses to natural influenza infection versus vaccination and another that documents the lack of protective immunity against measles, mumps, and varicella among lung transplant recipients. Cover design by Megan Llewellyn, Duke University Section of Surgical Disciplines.
Islet cell transplantation hits a milestone
Lara C. Pullen PHD
doi : 10.1111/ajt.16039
Volume 21, Issue 8 p. 2625-2626
This month's installment of “The AJT Report” discusses the controversy behind pending regulation of allogeneic pancreatic islet cells as a treatment for brittle type 1 diabetes, and provides an update on a recent governmental hearing concerning organ procurement organizations.
Senescence and aging of solid organs? Blame the immune system!
Xian C. Li MD, PHD
doi : 10.1111/ajt.16040
Volume 21, Issue 8 p. 2627-2627
Senescence and aging of immune cells drive systemic aging and age-related organ injuries.
The future of SARS-CoV-2 vaccines in transplant recipients: To be determined
Emily A. Blumberg,Oriol Manuel,Martina Sester,Michael G. Ison
doi : 10.1111/ajt.16598
Volume 21, Issue 8 p. 2629-2630
The increasing availability of SARS-CoV-2 vaccines has been heralded as the intervention that will finally stem the COVID-19 pandemic. However, it is unclear how immunosuppressed patients, including solid organ transplant recipients, will respond to vaccination. Given the smaller numbers of affected patients, compared with vaccine trials in the general population, the changing epidemiology of the pandemic with the emergence of concerning viral variants, and greater precautionary measure adherence, it may be difficult to determine efficacy in this population. Consequently, the assessment of immunogenicity, including measurement of antibodies to the spike receptor-binding domain and evaluation of cellular responses, provides important information to define the host response to this vaccine.
Diversity of antibody responses after influenza infection or vaccination—Needed or nice to have?
Barbara C. G?¤rtner,Martina Sester
doi : 10.1111/ajt.16554
Volume 21, Issue 8 p. 2631-2632
Influenza is a major threat in solid organ transplant recipients with significant morbidity and mortality.1 Yearly vaccination is therefore key to convey protection toward the circulating strains, and to prevent severe disease. In addition, natural exposure and regular vaccination may contribute to an increasing diversity of the immune response by accumulation of cross-protective immunological memory toward different strains. Unfortunately, vaccination in transplant recipients is challenging due to suboptimal vaccine efficacy which is significantly lower than in the general population.1 Thus, efforts toward improving vaccine responses will benefit from a detailed knowledge on the diversity of the immune response conveyed by vaccines or natural infection.
Optimizing virus protection in lung transplant recipients: Don’t drop the ball
Keith C. Meyer,Robin K. Avery
doi : 10.1111/ajt.16609
Volume 21, Issue 8 p. 2633-2634
The SARS-CoV-2 pandemic has brought the threat of viral infections to the fore. Even seemingly healthy, young individuals can die if they contract the virus,1 and immunocompromised individuals may be at greater risk of a fatal outcome should they become infected.2 But many other viruses pose potential threats to the well-being of solid organ transplant recipients. Chief among viral threats to lung transplant recipients are cytomegalovirus and community-acquired respiratory viruses. Fortunately, we have developed strategies to prevent or blunt the impact of cytomegalovirus on lung transplant recipients,3 but a high degree of vigilance must be maintained to screen and prevent the passage of transmissible viruses from donor to recipient.4
Risk and reward: Balancing safety and maximizing lung donors during the COVID-19 pandemic
Ricardo M. La Hoz,Lara A. Danziger-Isakov,David K. Klassen,Marian G. Michaels
doi : 10.1111/ajt.16575
Volume 21, Issue 8 p. 2635-2636
During the early phase of the Coronavirus Disease 2019 (COVID-19) pandemic, there was an abrupt decline in the number of transplants in the United States.1 The possibility of donor-derived COVID-19 was one of the contributing factors and a consequence of the limited availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) donor testing. As solid organ transplant rates have returned to the pre-pandemic time despite the on-going pandemic, the optimal approach to screen solid organ donors for SARS-CoV-2 is uncertain. Ideally, donor screening should minimize the risk of disease transmission and maximize organ utilization.
The limits of refusal: An ethical review of solid organ transplantation and vaccine hesitancy
Olivia S. Kates,Erica J. Stohs,Steven A. Pergam,Robert M. Rakita,Marian G. Michaels,Cameron R. Wolfe,Lara Danziger-Isakov,Michael G. Ison,Emily A. Blumberg,Raymund R. Razonable,Elisa J. Gordon,Douglas S. Diekema
doi : 10.1111/ajt.16472
Volume 21, Issue 8 p. 2637-2645
Patients pursuing solid organ transplantation are encouraged to receive many vaccines on an accelerated timeline. Vaccination prior to transplantation offers the best chance of developing immunity and may expand the pool of donor organs that candidates can accept without needing posttransplant therapy. Furthermore, transplant recipients are at greater risk for acquiring vaccine-preventable illnesses or succumbing to severe sequelae of such illnesses. However, a rising rate of vaccine refusal has challenged transplant centers to address the phenomenon of vaccine hesitancy. Transplant centers may need to consider adopting a policy of denial of solid organ transplantation on the basis of vaccine refusal for non-medical reasons (i.e., philosophical or religious objections or personal beliefs that vaccines are unnecessary or unsafe). Arguments supporting such a policy are motivated by utility, stewardship, and beneficence. Arguments opposing such a policy emphasize justice and respect for persons, and seek to avoid worsening inequities or medical coercion. This paper examines these arguments and situates them within the special cases of pediatric transplantation, emergent transplantation, and living donation. Ultimately, a uniform national policy addressing vaccine refusal among transplant candidates is needed to resolve this ethical dilemma and establish a consistent, fair, and standard approach to vaccine refusal in transplantation.
Public discourse and policy change: Absence of harm from increased oversight and transparency in OPO performance
Brianna L. Doby,Katie Ross-Driscoll,Marion Shuck,Matthew Wadsworth,Christine M. Durand,Raymond J. Lynch
doi : 10.1111/ajt.16527
Volume 21, Issue 8 p. 2646-2652
The Centers for Medicare and Medicaid Services announced changes to the Final Rule for organ procurement organizations (OPOs) in November 2020, after a 23-month period of public debate. One concern among transplant stakeholders was that public focus on OPO underperformance would harm deceased donation. Using CDC-WONDER data, we studied whether donation performance dropped during the era of public debate about OPO reform (December 2018–February 2020). Overall OPO performance as measured relative to cause, age, and location-consistent deaths rose by 12.3% in 2019, compared to a median annual change of 2.5% 2009–2019. Organ recoveries exceeded seasonally adjusted forecasts by 4.2% in the first half of 2019, by 8.1% following the Executive Order issuing a mandate for OPO metric reform, and by 14.1% between the Notice of Public Rule Making and the onset of COVID-19-related systemic disruptions. We describe changes in donor phenotype in the period of increased performance; improvement was greatest for older and donation after cardiac death (DCD) donors, and among decedents who did not have a drug-related mechanism of death. In summary, performance during an era of intense public debate and proposed regulatory changes yielded 692 additional donors over expectations, and no detriment to organ donation was observed.
“Time is tissue”—A minireview on the importance of donor nephrectomy, donor hepatectomy, and implantation times in kidney and liver transplantation
Line Heylen,Jacques Pirenne,Maarten Naesens,Ben Sprangers,Ina Jochmans
doi : 10.1111/ajt.16580
Volume 21, Issue 8 p. 2653-2661
Donor organs are exposed to sequential temperature changes during the transplantation process. The role of donor warm ischemia and cold ischemia times on post-transplant outcomes has been extensively studied. Much less attention has been paid to the transient ischemia occurring during donor organ removal and implantation. Recently, it has become clear that prolonged donor nephrectomy and implantation time are independently associated with delayed graft function after kidney transplantation. In addition, implantation time correlates with post-transplant kidney graft function, histology, and survival. Similar detrimental associations of donor hepatectomy and implantation time with early allograft dysfunction, ischemic cholangiopathy, and graft and patient survival after liver transplantation have been demonstrated. This review details kidney and liver temperature changes occurring during procurement and transplantation. It summarizes the effects of the ischemia the kidney and liver sustain during these phases on short- and long-term post-transplant outcomes, advocating the standardized reporting of donor hepatectomy, donor nephrectomy, and implantation times in (inter)national registries. The review also explores strategies to protect the graft from this ischemic injury.
Comprehensive analysis of the immunomodulatory effects of rapamycin on human T cells in graft-versus-host disease prophylaxis
Gr?©gory Ehx,Caroline Ritacco,Muriel Hannon,Sophie Dubois,Loic Delens,Evelyne Willems,Sophie Servais,Pierre Drion,Yves Beguin,Fr?©d?©ric Baron
doi : 10.1111/ajt.16505
Volume 21, Issue 8 p. 2662-2674
Graft-versus-host disease (GVHD) is a major cause of toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). While rapamycin (RAPA) is commonly used in GVHD prophylaxis in combination with a calcineurin inhibitor (CNI), the understanding of its mechanism of action on human T cells is still incomplete. Here, we performed an extensive analysis of RAPA effects on human T cells in a humanized mouse model of GVHD, in ex-vivo T cell cultures and in patients given RAPA plus tacrolimus as GVHD prophylaxis after nonmyeloablative allo-HCT. We demonstrate that RAPA mitigates GVHD by decreasing T cell engraftment and differentiation, inhibiting CD8+ T cell activation and increasing the long-term IL-2 secretion, thereby supporting regulatory T cell (Treg) proliferation. In contrast, graft-versus-leukemia effects were not abrogated, as RAPA-treated T cells had increased resistance to apoptosis and retained their effector function and proliferative capacity upon re-stimulation. Importantly, we found that RAPA impact on Treg and CD8+ T cells was closely dependent upon IL-2 signaling and that therapeutic options interfering with IL-2, such as calcineurin inhibitors, antagonize the IL-2-dependent promotion of Treg mediated by RAPA. Our results suggest that RAPA immunological efficacy could be improved in combination with drugs having possible synergistic effects such as the hypomethylating agent 5-azacytidine.
A short course of tofacitinib sustains the immunoregulatory effect of CTLA4-Ig in the presence of inflammatory cytokines and promotes long-term survival of murine cardiac allografts
Marcos Iglesias,Saami Khalifian,Byoung C. Oh,Yichuan Zhang,Devin Miller,Sarah Beck,Gerald Brandacher,Giorgio Raimondi
doi : 10.1111/ajt.16456
Volume 21, Issue 8 p. 2675-2687
Costimulation blockade-based regimens are a promising strategy for management of transplant recipients. However, maintenance immunosuppression via CTLA4-Ig monotherapy is characterized by high frequency of rejection episodes. Recent evidence suggests that inflammatory cytokines contribute to alloreactive T cell activation in a CD28-independent manner, a reasonable contributor to the limited efficacy of CTLA4-Ig. In this study, we investigated the possible synergism of a combined short-term inhibition of cytokine signaling and CD28 engagement on the modulation of rejection. Our results demonstrate that the JAK/STAT inhibitor tofacitinib restored the immunomodulatory effect of CTLA4-Ig on mouse alloreactive T cells in the presence of inflammatory cytokines. Tofacitinib exposure conferred dendritic cells with a tolerogenic phenotype reducing their cytokine secretion and costimulatory molecules expression. JAK inhibition also directly affected T cell activation. In vivo, the combination of CTLA4-Ig and tofacitinib induced long-term survival of heart allografts and, importantly, it was equally effective when using grafts subjected to prolonged ischemia. Transplant survival correlated with a reduction in effector T cells and intragraft accumulation of regulatory T cells. Collectively, our studies demonstrate a powerful synergism between CTLA4-Ig and tofacitinib and suggest their combined use is a promising strategy for improved management of transplanted patients.
Uninephrectomy and class II PI3K-C2? inactivation synergistically protect against obesity, insulin resistance and liver steatosis in mice
Samira Alliouachene,Julius E. Kieswich,Benoit Bilanges,Kieran McCafferty,Christoph Thiemermann,Bart Vanhaesebroeck,Muhammad M. Yaqoob
doi : 10.1111/ajt.16470
Volume 21, Issue 8 p. 2688-2697
Uninephrectomy (UNx) in living kidney donors for transplantation is now routine clinical practice. While chronic kidney disease, due to bilateral kidney dysfunction, is associated with insulin resistance, liver steatosis, and type 2 diabetes, the metabolic impact of UNx remains unclear. To better understand the crosstalk between the kidney and insulin target tissues, we studied the metabolic consequences of UNx and the potential involvement of class II PI3K-C2?², the inactivation of which has been reported to result in insulin sensitization. Mice underwent UNx or sham operation followed by either normal chow or high-fat diet (HFD). Seventeen weeks post-UNx, mice showed improved glucose tolerance, insulin sensitivity, and decreased HFD-induced liver steatosis. This was associated with an enhanced serum FGF21 and insulin-stimulated Akt signaling in the liver and muscle of both lean and obese mice. Remarkably, the combination of UNx and PI3K-C2?² inactivation protected against HFD-induced obesity and further potentiated the metabolic improvement observed in WT UNx mice correlating with a synergistic increase in metabolic tissues of (1) insulin-stimulated Akt signaling (2) FGFR1 and ?²Klotho expression. We demonstrated a potential beneficial effect of kidney donation and more effectively with PI3K-C2?² inactivation to protect against metabolic disorders through a mutual insulin/FGF21 sensitization
Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function
Kai Nishime,Chika Miyagi-Shiohira,Kazuho Kuwae,Yoshihito Tamaki,Tasuku Yonaha,Mayuko Sakai-Yonaha,Issei Saitoh,Masami Watanabe,Hirofumi Noguchi
doi : 10.1111/ajt.16401
Volume 21, Issue 8 p. 2698-2708
Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H2S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H2S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.
Natural influenza infection produces a greater diversity of humoral responses than vaccination in immunosuppressed transplant recipients
Cedric Hirzel,Andrzej Chruscinski,Victor H. Ferreira,Arnaud G. L’Huillier,Yochiro Natori,Sang H. Han,Elisa Cordero,Atul Humar,Deepali Kumar,Influenza in Transplant Study Group
doi : 10.1111/ajt.16503
Volume 21, Issue 8 p. 2709-2718
The humoral immune response to influenza virus infection is complex and may be different compared to the antibody response elicited by vaccination. We analyzed the breadth of IgG and IgA responses in solid organ transplant (SOT) recipients to a diverse collection of 86 influenza antigens elicited by natural influenza A virus (IAV) infection or by vaccination. Antibody levels were quantified using a custom antigen microarray. A total of 120 patients were included: 80 IAV infected (40 A/H1N1 and 40 A/H3N2) and 40 vaccinated. Based on hierarchical clustering analysis, infection with either H1N1 or H3N2 virus showed a more diverse antibody response compared to vaccination. Similarly, H1N1-infected individuals showed a significant IgG response to 27.9% of array antigens and H3N2-infected patients to 43.0% of antigens, whereas vaccination elicited a less broad immune response (7.0% of antigens). Immune responses were not exclusively targeting influenza hemagglutinin (HA) proteins but were also directed against conserved influenza antigens. Serum IgA responses followed a similar profile. This study provides novel data on the breadth of antibody responses to influenza. We also found that the diversity of response is greater in influenza-infected rather than vaccinated patients, providing a potential mechanistic rationale for suboptimal vaccine efficacy in this population.
Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus
Ayelet Grupper,Liane Rabinowich,Doron Schwartz,Idit F. Schwartz,Merav Ben-Yehoyada,Moshe Shashar,Eugene Katchman,Tami Halperin,Dan Turner,Yaacov Goykhman,Oren Shibolet,Sharon Levy,Inbal Houri,Roni Baruch,Helena Katchman
doi : 10.1111/ajt.16615
Volume 21, Issue 8 p. 2719-2726
COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17–2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09–1.86]), maintenance with triple immunosuppression (1.43 [1.06–2.15]), and regimen that includes mycophenolate (1.47 [1.26–2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.
Cellular and humoral response after MRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients
David Cucchiari,Natalia Egri,Marta Bodro,Sabina Herrera,Jimena Del Risco-Zevallos,Joaquim Casals-Urquiza,Frederic Cofan,Asunci?³n Moreno,Jordi Rovira,Elisenda Banon-Maneus,Maria J. Ramirez-Bajo,Pedro Ventura-Aguiar,Anna P?©rez-Olmos,Marta Garcia-Pascual,Mariona Pascal,Anna Vilella,Antoni Trilla,Jos?© R?os,Eduard Palou,Manel Juan,Beatriu Bay?©s,Fritz Diekmann
doi : 10.1111/ajt.16701
Volume 21, Issue 8 p. 2727-2739
According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-na?¯ve. After vaccination, na?¯ve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.
COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative
Charles Varnell Jr,Lyndsay A. Harshman,Laurie Smith,Chunyan Liu,Shiran Chen,Samhar Al-Akash,Gina-Marie Barletta,Craig Belsha,Paul Brakeman,Abanti Chaudhuri,Paul Fadakar,Rouba Garro,Caroline Gluck,Jens Goebel,David Kershaw,Debora Matossian,Corina Nailescu,Hiren P. Patel,Cozumel Pruette,Saritha Ranabothu,Nancy Rodig,Jodi Smith,Judith Sebestyen VanSickle,Patricia Weng,Lara Danziger-Isakov,David K. Hooper,Michael Seifert
doi : 10.1111/ajt.16501
Volume 21, Issue 8 p. 2740-2748
There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.
SARS-CoV-2-specific serological and functional T cell immune responses during acute and early COVID-19 convalescence in solid organ transplant patients
Alexandre Fav? ,Laura Donadeu,Nuria Sab?©,Vincent Pernin,Jos?© Gonz??lez-Costello,Laura Llad?³,Maria Meneghini,Xavier Charmetant,Elena Garc?a-Romero,Alba Cachero,Alba Torija,Ronny Rodriguez-Urquia,Elena Crespo,Iris Teubel,Edoardo Melilli,Nuria Montero,Anna Manonelles,Rosemarie Preyer,Kevin Strecker,Anne Ovize,Juan J. Lozano,Julia Sidorova,Josep M. Cruzado,Moglie Le Quintrec,Olivier Thaunat,Oriol Bestard
doi : 10.1111/ajt.16570
Volume 21, Issue 8 p. 2749-2761
The description of protective humoral and T cell immune responses specific against SARS-CoV-2 has been reported among immunocompetent (IC) individuals developing COVID-19 infection. However, its characterization and determinants of poorer outcomes among the at-risk solid organ transplant (SOT) patient population have not been thoroughly investigated. Cytokine-producing T cell responses, such as IFN-?³, IL-2, IFN-?³/IL-2, IL-6, IL-21, and IL-5, against main immunogenic SARS-CoV-2 antigens and IgM/IgG serological immunity were tracked in SOT (n = 28) during acute infection and at two consecutive time points over the following 40 days of convalescence and were compared to matched IC (n = 16) patients admitted with similar moderate/severe COVID-19. We describe the development of a robust serological and functional T cell immune responses against SARS-CoV-2 among SOT patients, similar to IC patients during early convalescence. However, at the infection onset, SOT displayed lower IgG seroconversion rates (77% vs. 100%; p = .044), despite no differences on IgG titers, and a trend toward decreased SARS-CoV-2-reactive T cell frequencies, especially against the membrane protein (7 [0–34] vs. 113 [15–245], p = .011, 2 [0–9] vs. 45 [5–74], p = .009, and 0 [0–2] vs. 13 [1–24], p = .020, IFN-?³, IL-2, and IFN-?³/IL-2 spots, respectively). In summary, our data suggest that despite a certain initial delay, SOT population achieve comparable functional immune responses than the general population after moderate/severe COVID-19.
COVID-19 in solid organ transplant recipients: A national cohort study from Sweden
John M. S?¸fteland,Gustav Friman,Bengt von Zur-M?¼hlen,Bo-G?¶ran Ericzon,Carin Wallquist,Kristjan Karason,Vanda Friman,Jan Ekelund,Marie Felldin,Jesper Magnusson,Ida Haugen L?¶fman,Andreas Schult,Emily de Coursey,Susannah Leach,Hanna Jacobsson,Jan-?…ke Liljeqvist,Ali R. Biglarnia,Per Lindn?©r,Mihai Oltean
doi : 10.1111/ajt.16596
Volume 21, Issue 8 p. 2762-2773
Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.
COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study
Madeleine R. Heldman,Olivia S. Kates,Kassem Safa,Camille N. Kotton,Sarah J. Georgia,Julie M. Steinbrink,Barbara D. Alexander,Marion Hemmersbach-Miller,Emily A. Blumberg,Maria M. Crespo,Ashrit Multani,Angelica V. Lewis,Omer Eugene Beaird,Brandy Haydel,Ricardo M. La Hoz,Lisset Moni,Yesabeli Condor,Sandra Flores,Carlos G. Munoz,Juan Guitierrez,Esther I. Diaz,Daniela Diaz,Rodrigo Vianna,Giselle Guerra,Matthias Loebe,Robert M. Rakita,Maricar Malinis,Marwan M. Azar,Vagish Hemmige,Margaret E. McCort,Zohra S. Chaudhry,Pooja Singh,Kailey Hughes,Arzu Velioglu,Julie M. Yabu,Jose A. Morillis,Sapna A. Mehta,Sajal D. Tanna,Michael G. Ison,Rade Tomic,Ariella Candace Derenge,David van Duin,Adrienne Maximin,Carlene Gilbert,Jason D. Goldman,Sameep Sehgal,Dana Weisshaar,Reda E. Girgis,Joanna Nelson,Erika D. Lease,Ajit P. Limaye,Cynthia E. Fisher,on behalf of the UW COVID-19 SOT Study Team
doi : 10.1111/ajt.16692
Volume 21, Issue 8 p. 2774-2784
Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0–2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0–11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.
T cell–mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19
Mario Fern??ndez-Ruiz,Beatriz Olea,Patricia Almendro-V??zquez,Estela Gim?©nez,Alberto Marcacuzco,Rafael San Juan,Iago Justo,Jorge Calvo-Pulido,?�lvaro Garc?a-Sesma,Alejandro Manrique,Oscar Caso,F?©lix Cambra,Paloma Talayero,Francisco L?³pez-Medrano,Mar?a Jos?© Remigia,Tamara Ruiz-Merlo,Patricia Parra,Estela Paz-Artal,Carlos Jim?©nez,Carmelo Loinaz,David Navarro,Roc?o Laguna-Goya,Jos?© M. Aguado
doi : 10.1111/ajt.16708
Volume 21, Issue 8 p. 2785-2794
Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell–mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-?³ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-?³-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-?³-producing SFUs and time from diagnosis (Spearman's rho: −0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell–mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable—but declining over time—SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.
Third-party bone marrow–derived mesenchymal stromal cell infusion before liver transplantation: A randomized controlled trial
Federica Casiraghi,Norberto Perico,Manuel A. Podest? ,Marta Todeschini,Marco Zambelli,Michele Colledan,Stefania Camagni,Stefano Fagiuoli,Antonio D. Pinna,Matteo Cescon,Valentina Bertuzzo,Lorenzo Maroni,Martino Introna,Chiara Capelli,Josee T. Golay,Marina Buzzi,Marilena Mister,Pamela Y. R. Ordonez,Matteo Breno,Caterina Mele,Alessandro Villa,Giuseppe Remuzzi,the MSC-LIVER Study Group
doi : 10.1111/ajt.16468
Volume 21, Issue 8 p. 2795-2809
Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow–derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56bright NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375.
Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes
Phuoc H. Pham,Lily N. Stalter,Eric J. Martinez,Jesse F. Wang,Bridget M. Welch,Glen Leverson,Nicholas Marka,Talal Al-Qaoud,Didier Mandelbrot,Sandesh Parajuli,Hans W. Sollinger,Dixon Kaufman,Robert R. Redfield,Jon S. Odorico
doi : 10.1111/ajt.16462
Volume 21, Issue 8 p. 2810-2823
Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.
Long-term kidney transplant graft survival—Making progress when most needed
Emilio D. Poggio,Joshua J. Augustine,Susana Arrigain,Daniel C. Brennan,Jesse D. Schold
doi : 10.1111/ajt.16463
Volume 21, Issue 8 p. 2824-2832
Current short-term kidney post–transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000–2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014–2017 (1995–1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995–1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995–1999 to an estimated 19.2 years for transplants in 2014–2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.
Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial
Oriol Bestard,Maria Meneghini,Elena Crespo,Frederike Bemelman,Martina Koch,Hans D. Volk,Ondrej Viklicky,Magali Giral,Bernhard Banas,Juan C. Ruiz,Edoardo Melilli,Liu Hu,Raphael van Duivenvoorden,Bj?rn Nashan,Friedrich Thaiss,Natalie M. Otto,Gantuja Bold,Maik Stein,Anett Sefrin,Nils Lachmann,Petra Hruba,Lucia Stranavova,Sophie Brouard,Cécile Braudeau,Gilles Blancho,Miriam Banas,Juan Irure,Sophia Christakoudi,Alberto Sanchez-Fueyo,Kathryn J. Wood,Petra Reinke,Josep M. Griny?
doi : 10.1111/ajt.16563
Volume 21, Issue 8 p. 2833-2845
Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-? ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E?) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E? (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E? patients, notably E?/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E?/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.
Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders
Cecilia Nakid-Cordero,Sylvain Choquet,Nicolas Gauthier,Noureddine Balegroune,Nadine Tarantino,V?©ronique Morel,Nadia Arzouk,Sonia Burrel,G?©raldine Rousseau,Fr?©d?©ric Charlotte,Martin Larsen,Vincent Vieillard,Brigitte Autran,V?©ronique Leblond,Am?©lie Guihot,for the K-VIROGREF Study Group
doi : 10.1111/ajt.16547
Volume 21, Issue 8 p. 2846-2863
EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFN?³ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4+<300 cells/mm3, p < .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm3) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.
Immunity to varicella, measles, and mumps in patients evaluated for lung transplantation
Haley P. Hostetler,Megan L. Neely,Elizabeth Lydon,Lara A. Danziger-Isakov,Jamie L. Todd,Scott M. Palmer
doi : 10.1111/ajt.16602
Volume 21, Issue 8 p. 2864-2870
Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17–48 years old) was negatively associated with immunity for VZV (OR 4.54, p < .001), measles (OR 15.45, p < .001) and mumps (OR 3.1, p < .001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p < .001) and measles (OR 2.32, p = .010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.
Long-term shedding of viable SARS-CoV-2 in kidney transplant recipients with COVID-19
Ilies Benotmane,Simone Risch,C?©cile Doderer-Lang,Sophie Caillard,Samira Fafi-Kremer
doi : 10.1111/ajt.16636
Volume 21, Issue 8 p. 2871-2875
The exact duration of viable SARS-CoV-2 shedding in kidney transplant recipients (KTRs) remains unclear. Here, we retrospectively investigated this issue using cell cultures of SARS-CoV-2 RT-PCR-positive nasopharyngeal samples (n = 40) obtained from 16 KTRs with symptomatic COVID-19 up to 39 days from symptom onset. A length of viable SARS-CoV-2 shedding >3 weeks from the onset of symptoms was identified in four KTRs (25%). These results suggest that a significant proportion of KTRs can shed viable SARS-CoV-2 for at least 3 weeks, which may favor the emergence of new variants. Based on these data, we recommend prolonging the isolation of KTRs with COVID-19 until negative SARS-CoV-2 RT-PCR testing.
Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients
Ar??nzazu Caballero-Marcos,Magdalena Salcedo,Roberto Alonso-Fern??ndez,Manuel Rodr?guez-Per??lvarez,Mar?a Olmedo,Javier Graus Morales,Valent?n Cuervas-Mons,Alba Cachero,Carmelo Loinaz-Segurola,Mercedes I?±arrairaegui,Llu?s Castells,Sonia Pascual,Carmen Vinaixa-Aun?©s,Roc?o Gonz??lez-Grande,Alejandra Otero,Santiago Tom?©,Javier Tejedor-Tejada,Jos?© Mar?a ?�lamo-Mart?nez,Luisa Gonz??lez-Di?©guez,Flor Nogueras-Lopez,Gerardo Blanco-Fern??ndez,Gema Mu?±oz-Bartolo,Francisco Javier Bustamante,Emilio F??brega,Mario Romero-Crist?³bal,Rosa Martin-Mateos,Julia Del Rio-Izquierdo,Ana Arias-Milla,Laura Calatayud,Alberto A. Marcacuzco-Quinto,V?ctor Fern??ndez-Alonso,Concepci?³n G?³mez-Gavara,Jordi Colmenero,Patricia Mu?±oz,Jos?© A. Pons,the Spanish Society of Liver Transplantation (SETH)
doi : 10.1111/ajt.16599
Volume 21, Issue 8 p. 2876-2884
The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.
Donor to recipient transmission of SARS-CoV-2 by lung transplantation despite negative donor upper respiratory tract testing
Daniel R. Kaul,Andrew L. Valesano,Joshua G. Petrie,Rommel Sagana,Dennis Lyu,Jules Lin,Emily Stoneman,Lane M. Smith,Paul Lephart,Adam S. Lauring
doi : 10.1111/ajt.16532
Volume 21, Issue 8 p. 2885-2889
We describe a case of proven transmission of SARS-CoV-2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS-CoV-2 and tested negative by reverse transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT-PCR testing for SARS-CoV-2 on an NP swab specimen was non-reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID-19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health-care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS-CoV-2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.
Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient
Lavanya Yohanathan,Cristina C. Campioli,Omar Y. Mousa,Kymberly Watt,Daniel Z. P. Friedman,Vijay Shah,Resham Ramkissoon,Alexander S. Hines,Patrick S. Kamath,Raymund R. Razonable,Andrew D. Badley,Erin S. DeMartino,Michael J. Joyner,Rondell Graham,Paschalis Vergidis,Doug A. Simonetto,William Sanchez,Timucin Taner,Julie K. Heimbach,Elena Beam,Michael D. Leise
doi : 10.1111/ajt.16582
Volume 21, Issue 8 p. 2890-2894
Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.
Hepatitis C–associated focal proliferative glomerulonephritis in an aviremic recipient of a hepatitis C–positive antibody donor liver
Humberto Bohorquez,Juan C. Q. Velez,Mark Lusco,Jennifer Scheuermann,Ari J. Cohen
doi : 10.1111/ajt.16565
Volume 21, Issue 8 p. 2895-2899
Shortage of organs for liver transplantation (LT) and the availability of highly efficient pan-genotypic direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have allowed the use of livers from HCV-positive antibody/negative nucleic acid test donors (dHCV Ab+/NAT−) into aviremic HCV recipients over the last few years. We report the case of a patient who received an LT from an HCV Ab+/NAT− donor and, after HCV viremic conversion, developed a nephrotic syndrome due to a focal proliferative glomerulonephritis early after LT. Patient's renal function and proteinuria resolved after successful treatment with DAAs. Renal and hepatic function remain normal over 24 months of follow-up. This case restates the success of LT using livers from dHCV Ab+/NAT− in aviremic recipients in the context of DAAs while illustrating the risk for potential complications associated with the HCV transmission and reinforcing the importance of early initiation of anti-HCV therapy.
Excess death estimates in patients with end-stage renal disease — United States, February–August 2020
Robert Ziemba,Kyle N. Campbell,Tsu-Hsuan Yang,Sara E. Schaeffer,Kelly M. Mayo,Paul McGann,Shalon Quinn,Jesse Roach,Edwin D. Huff
doi : 10.1111/ajt.16041
Volume 21, Issue 8 p. 2900-2904
This article describes an estimated 6953–10 316 excess deaths among individuals with end-stage renal disease during the early months of the COVID-19 pandemic in February 2020–August 2020 (compared to death rates prior to the pandemic). Notably, the estimated number of excess deaths was reported as 10.8–16.6 per 1000 individuals on dialysis and 2.6–5.5 per 1000 individuals with a prior kidney transplantation. Although not adjusted for confounders, these data suggest that the immunosuppression associated with kidney transplantation is not a dominant determinant of outcomes associated with COVID-19 in this population.
A rare hepatic malignancy in childhood treated with living donor liver transplantation
Jennifer L. Carpenter,Nada A. Yazigi,Thomas M. Fishbein,Juan F. Guerra
doi : 10.1111/ajt.16539
Volume 21, Issue 8 p. 2905-2907
Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus: No cause for alarm
Sherif Beniameen Mossad
doi : 10.1111/ajt.16687
Volume 21, Issue 8 p. 2908-2908
Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus: Not alarming, but should be taken gravely
Ayelet Grupper,Helena Katchman
doi : 10.1111/ajt.16710
Volume 21, Issue 8 p. 2909-2909
Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients
Noam Tau,Dafna Yahav,Shira Schneider,Benaya Rozen-Zvi,Marwan Abu Sneineh,Ruth Rahamimov
doi : 10.1111/ajt.16700
Volume 21, Issue 8 p. 2910-2912
Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients
Smaragdi Marinaki,Stamatis Adamopoulos,Dimitrios Degiannis,Sotirios Roussos,Ioanna D. Pavlopoulou,Angelos Hatzakis,Ioannis N. Boletis
doi : 10.1111/ajt.16607
Volume 21, Issue 8 p. 2913-2915
Effectiveness of SARS-CoV-2 vaccination in fully vaccinated solid organ transplant recipients
Maricar Malinis,Elizabeth Cohen,Marwan M. Azar
doi : 10.1111/ajt.16713
Volume 21, Issue 8 p. 2916-2918
Impaired anti-SARS-CoV-2 humoral and cellular immune response induced by Pfizer-BioNTech BNT162b2 mRNA vaccine in solid organ transplanted patients
Monica Miele,Rosalia Bus? ,Giovanna Russelli,Maria Concetta Sorrentino,Mariangela Di Bella,Francesca Timoneri,Alessandra Mularoni,Giovanna Panarello,Patrizio Vitulo,Pier Giulio Conaldi,Matteo Bulati
doi : 10.1111/ajt.16702
Volume 21, Issue 8 p. 2919-2921
