Background The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. Methods We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p<0.001], congestive heart failure [aOR 3.2, 95%CI 1.4-7.0, p=0.004], chronic lung disease [aOR 2.5, 95%CI 1.2-5.2, p=0.018], obesity [aOR 1.9, 95% CI 1.0-3.4, p=0.039]) and presenting findings (lymphopenia [aOR 1.9, 95%CI 1.1-3.5, p=0.033], abnormal chest imaging [aOR 2.9, 95%CI 1.1-7.5, p=0.027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. Conclusions Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Tacrolimus gained FDA approval for use in liver transplantation in 1994 and, approximately 3 years later, was approved for the prevention of acute rejection in kidney transplantation. Over the last decade tacrolimus has become the calcineurin inhibitor of choice for the prevention of rejection in renal transplantation. The objective of this study was to provide a review and update of the literature on the use of tacrolimus in renal transplantation. Numerous clinical trials have shown tacrolimus to be superior to cyclosporine in the prevention of acute rejection and recent trials have demonstrated superiority of tacrolimus over cyclosporine in terms of allograft survival. Post-transplant diabetes remains more common with tacrolimus than cyclosporine, despite lower doses of both tacrolimus and corticosteroids. A novel once-daily dosage form of tacrolimus has recently been developed and is approved for use in Europe. Tacrolimus remains an important immunosuppressant for the prevention of acute rejection. The prolonged-release formulation may improve compliance and possibly long-term outcomes.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center‐specific protocol, provider expertise, insurance formularies, ability to cover co‐pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off‐label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

Viruses are the leading cause of infections after solid organ transplant. The antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have been ascribed to a variety of mechanisms and historical data have supported their use over other immunosuppressants for a myriad of viruses. Herein, we summarize the most current data to highlight the role of mTORis in the management of viral infections after solid organ transplant. The mTORis play a clear role in the management of cytomegalovirus, and have data supporting their potential use for BK virus and human herpesvirus 8-related Kaposi sarcoma. No data definitively supports mTORis for use in Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder or hepatitis C virus viral replication. Although theoretically an advantageous therapy for hepatitis C virus-related liver allograft fibrosis and human immunodeficiency virus, mTORi use specifically for these indications is less attractive with modern treatments currently available. Data surrounding mTORi efficacy in preventing rejection, and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.

Background Both prophylactic and preemptive oral valganciclovir therapy are effective for management of cytomegalovirus (CMV) post renal transplantation in the short-term. The long-term effect of either strategy is less well-defined. Methods We analyzed data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, post-transplant cardiovascular events, new-onset diabetes mellitus after transplant (NODAT), achievement of goal blood pressure, change in body mass index (BMI), interstitial fibrosis/tubular atrophy (IF/TA) and change in renal function. The analysis period was a 48-months post-transplant or date of death/graft loss, whichever was earlier. Results The primary outcome was similar between groups (83% prophylactic versus 81% preemptive, p = 0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared to none in the preemptive group (0%) died with a functioning graft, p=0.043. Conclusions Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately post-transplantation appears effective for patient and graft survival in the long-term. CMV-management is one of many therapeutic strategies incorporated into a renal transplantation protocol which often differs among institutions, and the decision as to which approach to use remains center and resource specific. The increased incidence of death in the prophylactic group requires further investigation.