A Network for Advancing Prevention and Treatment of Infections Among Immunocompromised Individuals.

Importance: Immunocompromised individuals are a large and growing population who are at increased risk for infectious diseases. There has and continues to be a lack of focus on clinical trials to establish the safety and efficacy of therapies for infectious diseases in immunocompromised patients. The establishment of a US-based clinical trial network to improve the study and subsequent implementation of therapies and strategies to treat and prevent infections in immunocompromised individuals would address this gap in research infrastructure and jumpstart public and private investment.

Innovation in active and passive immunisation of people who are immunocompromised: a call to action.

The proportion of the population with immunocompromising conditions, who are at increased risk for complications from infectious diseases, continues to grow. Concurrently, outbreaks due to known and emerging pathogens are increasing. Vaccines are the foundation of infection prevention; however, attenuated immune responses in people who are immunocompromised necessitates innovation in design and delivery strategies.

Management of diarrhea in solid organ transplantation.

Purpose Of Review: Diarrhea is a common complaint in solid organ transplant recipients. We review both infectious and noninfectious causes of diarrhea and their management.

Recent Findings: Diagnostics for diarrhea have now commonly incorporated multiplex gastrointestinal panels that provide rapid testing and identification of pathogens.

Longitudinal Innate and Heterologous Adaptive Immune Responses to SARS-CoV-2 JN.1 in Transplant Recipients With Prior Omicron Infection: Limited Neutralization but Robust CD4 T-Cell Activity.

Background: Solid organ transplant (SOT) recipients are at increased risk for severe COVID-19 and often exhibit reduced vaccine efficacy due to chronic immunosuppression. As new SARS-CoV-2 variants emerge, understanding immune responses following natural infection remains critical for informing protection strategies in this vulnerable population. We conducted a longitudinal study of SOT recipients who had recovered from Omicron BA.

Moving Beyond the Perfect Donor: An Interdisciplinary Approach to Optimizing Donor Utilization.

Background: Despite a growing demand for donor hearts, more than two-thirds of viable hearts are discarded in North America. Our initiative sought to improve donor heart utilization by reviewing institutional donor acceptance practices and implementing targeted interventions.

Objectives: Our aim was to increase donor heart utilization rate to 20% and reduce the rate of missed viable opportunities to ≤10% within a 12-month period, and assess the incidence of primary graft dysfunction preintervention and postintervention.

Feasibility and Safety of Ex Vivo Delivery of Rituximab to Lung Allografts in Transplant Recipients at High Risk for Epstein-Barr Virus-associated Posttransplant Lymphoproliferative Disorder.

Background: Ex vivo lung perfusion (EVLP) offers a novel platform for delivering targeted therapies directly to donor lungs before transplantation, potentially reducing systemic side effects. Our study evaluated the feasibility and safety of rituximab delivery to donor lungs from Epstein-Barr virus (EBV)-seropositive donors for transplantation into EBV-seronegative recipients (D/R) to reduce the risk of EBV-associated posttransplant lymphoproliferative disorder (PTLD), which remains a major obstacle in the transplant setting.

Methods: A pilot study was conducted involving 5 EBV-seronegative lung transplant recipients.

Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: Subgroup analysis of the phase 3 randomized SOLSTICE study.

Background: In the phase 3 SOLSTICE study (NCT02931539), maribavir was superior to investigator-assigned therapy (IAT) for confirmed cytomegalovirus viremia clearance at study week 8 in hematopoietic cell/solid organ transplant (HCT/SOT) recipients. We report additional efficacy and safety analyses from the SOT subgroup.

Methods: Eligible SOT recipients (n=211) received maribavir 400 mg twice daily (n=142) or IAT (n=69) for 8 weeks (12 weeks' follow-up).

Cell-mediated Immunity to Guide Primary Prophylaxis for CMV Infection in Organ Transplant Recipients: A Multicenter Single-arm Prospective Study.

Background: There are few interventional studies using CMV cell-mediated immunity (CMI) to guide antiviral prophylaxis. We assessed the Quantiferon-CMV (QTF-CMV) assay to guide CMV prophylaxis duration in high-risk organ transplant recipients.

Methods: A single-arm, multicenter, prospective interventional study including high-risk kidney, pancreas, liver, and heart transplant recipients who were either donor CMV-seropositive, recipient-seronegative (D + /R - ) or recipient-seropositive with antithymocyte globulin (R + /ATG) induction.

Impact of machine perfusion on transplant infectious diseases: New challenges and opportunities.

Preservation techniques that maintain the viability of an organ graft between retrieval from the donor and implantation into the recipient remain a critical aspect of solid organ transplantation. While traditionally preservation is accomplished with static cold storage, advances in ex vivo dynamic machine perfusion, both hypothermic and normothermic, have allowed for prolongation of organ viability and recovery of marginal organs effectively increasing the usable donor pool. However, the use of these novel machine perfusion technologies likely exposes the recipient to additional infectious risk either through clonal expansion of pathogens derived during organ recovery or de novo exogenous acquisition of pathogens while the organ remains on the machine perfusion circuit.

Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation.

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for 'exceptional distribution' could be met.

Longitudinal outcomes of COVID-19 in solid organ transplant recipients from 2020 to 2023.

Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) waves, including the impact of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, intensive care unit (ICU) admission, and 30-day and 1-year all-cause mortality.

Association between cytomegalovirus viremia and long-term outcomes in lung transplant recipients.

Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients.

COVID-19 Reinfection Has Better Outcomes Than the First Infection in Solid Organ Transplant Recipients.

Background: Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients.

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively.

SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain.

Background: Immune-suppressed solid-organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. SARS-CoV-2 variants Omicron BA.4/5 (BA.

Chronic Active Antibody-mediated Rejection: Opportunity to Determine the Role of Interleukin-6 Blockade.

Chronic active antibody-mediated rejection (caAMR) is arguably the most important cause of late kidney allograft failure. However, there are no US Food and Drug Administration (FDA)-approved treatments for acute or chronic AMR and there is no consensus on effective treatment. Many trials in transplantation have failed because of slow and/or inadequate enrollment, and no new agent has been approved by the FDA for transplantation in over a decade.

Respiratory viral infections including COVID-19 in solid organ transplantation.

Purpose Of Review: Respiratory viral infections are prevalent and contribute to significant morbidity and mortality among solid organ transplant (SOT) recipients. We review updates from literature on respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the SOT recipient.

Recent Findings: With the wider availability and use of molecular diagnostic tests, our understanding of the epidemiology and impact of respiratory viruses in the SOT population continues to expand.

Immunogenicity and Safety of Booster SARS-CoV-2 mRNA Vaccine Dose in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are susceptible to severe outcomes of Coronavirus disease 2019 (COVID-19). Most guidelines recommend a fourth dose (ie, booster) of COVID-19 vaccine to reduce the infection risk, and observational studies are needed to determine the immunogenicity and safety of the booster dose in this population. The primary outcome was to determine the quantitative anti-receptor-binding domain (RBD) antibody titers after the fourth dose of the COVID-19 vaccine.