Faculty Bibliography

Respiratory viruses-including SARS-CoV-2 (COVID-19), Respiratory Syncytial Virus (RSV), and Influenza-pose significant risks to immunocompromised patients, who experience attenuated vaccine responses and higher morbidity. To address evolving vaccine recommendations for the 2025-2026 season, the Infectious Diseases Society of America (IDSA), in collaboration with the Vaccine Integrity Project (VIP) and partner organizations, developed rapid guidelines for U.S.-licensed vaccines targeting these viruses. The guideline applies to adults and children with compromised immunity due to hematologic malignancy, solid organ or hematopoietic cell transplantation, autoimmune disease on immunosuppressants, HIV with severe immunosuppression, and similar conditions. Strong recommendations, supported by moderate-certainty evidence, endorse timely administration of age-appropriate COVID-19, RSV, and Influenza vaccines, with guidance on optimal timing relative to immunosuppressive therapy and transplantation. Co-administration of these vaccines is considered appropriate. Research gaps remain in immunogenicity, durability, and clinical effectiveness, particularly for patients receiving B-cell-depleting therapies or early post-transplant. Priority areas include defining correlates of protection, optimizing vaccine schedules, evaluating high-dose or adjuvanted formulations, and improving real-world effectiveness and safety data. Equity and access strategies are essential to ensure uptake among vulnerable populations. These guidelines aim to support evidence-based decision-making and highlight the need for harmonized, multi-virus research to inform tailored vaccination strategies for immunocompromised individuals.

Immunocompromised individuals face elevated risks of severe COVID-19, yet vaccination guidance for these populations continues to evolve. To support evidence-based decision-making for the 2025-2026 respiratory virus season, the Infectious Diseases Society of America (IDSA) convened a multidisciplinary panel to develop rapid guidelines on the use of U.S.-licensed COVID-19 vaccines in adults and children with hematologic malignancies, primary immunodeficiency, autoimmune disease on immunosuppressive therapy, HIV with severe immunosuppression, solid organ transplantation, hematopoietic cell transplantation (HCT), chimeric antigen receptor T-cell therapy (CAR-T), or solid-tumor chemotherapy. A systematic evidence review of studies published from June 2024 to July 2025 identified comparative data on vaccine effectiveness and safety. Using the GRADE framework, the panel evaluated seven observational effectiveness studies and four safety-focused studies. Across studies, COVID-19 vaccination was associated with reduced hospitalization (33-56% effectiveness), critical illness, mortality, and COVID-19-related outpatient or emergency care visits. Serious adverse events were rare, and available evidence did not show consistent increases in exacerbations of underlying immunocompromising conditions. Most studies had short follow-up durations, likely reflecting higher-end estimates of vaccine effectiveness. Given moderate certainty of benefit and low certainty of harm, the panel strongly recommends the 2025-2026 COVID-19 vaccine for all immunocompromised individuals aged ≥6 months, with timing tailored to immunosuppressive therapy, clinical stability, and community transmission levels. Adjunct strategies-including vaccination of household contacts and early antiviral access-remain essential. Research priorities include defining immunologic correlates of protection, evaluating durability, optimizing vaccine timing, and improving real-world effectiveness and safety data.

Organ shortage remains a major challenge in transplantation, and gene-edited pig organs offer a promising solution^1-3. Despite gene-editing, the immune reactions following xenotransplantation can still cause transplant failure⁴. To understand the immunological response of a pig-to-human kidney xenotransplantation, we conducted large-scale multi-omics profiling of the xenograft and the host's blood over a 61-day procedure in a brain-dead human (decedent) recipient. Blood plasmablasts, natural killer (NK) cells, and dendritic cells increased between postoperative day (POD)10 and 28, concordant with expansion of IgG/IgA B-cell clonotypes, and subsequent biopsy-confirmed antibody-mediated rejection (AbMR) at POD33. Human T-cell frequencies increased from POD21 and peaked between POD33-49 in the blood and xenograft, coinciding with T-cell receptor diversification, expansion of a restricted TRBV2/J1 clonotype and histological evidence of a combined AbMR and cell-mediated rejection at POD49. At POD33, the most abundant human immune population in the graft was CXCL9+ macrophages, aligning with IFN-γ-driven inflammation and a Type I immune response. In addition, we see evidence of interactions between activated pig-resident macrophages and infiltrating human immune cells. Xenograft tissue showed pro-fibrotic tubular and interstitial injury, marked by S100A6⁵, SPP1⁶ (Osteopontin), and COLEC11⁷, at POD21-POD33. Proteomics profiling revealed human and pig complement activation, with decreased human component after AbMR therapy with complement inhibition. Collectively, these data delineate the molecular orchestration of human immune responses to a porcine kidney, revealing potential immunomodulatory targets for improving xenograft survival.

We report a 62-year-old male who had a Heartware left ventricular assist device (LVAD) implantation and subsequently developed a persistent driveline infection, culminating in an abscess along the driveline site despite 18 months of antibiotic treatment. His situation was further complicated post-transplant by the onset of mediastinitis, linked to a previously undervalued Stenotrophomonas maltophilia infection. This report highlights the potential risks of heart transplantation in patients with unresolved LVAD driveline infections, particularly mediastinitis. The presence of existing driveline infections, combined with the immunosuppressed status of patients, necessitates aggressive surgical measures. Our treatment approach, involving multiple mediastinal washouts, omental flap use, antibiotic bead placement, and an extended post-discharge antibiotic regimen, led to a successful patient outcome. The case emphasizes the importance of thorough antimicrobial coverage for all identified pathogens post-transplantation and advocates for aggressive surgical intervention in managing postoperative complications associated with LVAD driveline infections.

Seasonal influenza vaccination elicits hemagglutinin (HA)-specific memory B (Bmem) cells, and although multiple Bmem cell populations have been characterized, considerable heterogeneity exists. We found that HA-specific human Bmem cells differed in the expression of surface marker FcRL5 and transcriptional factor T-bet. FcRL5⁺T-bet⁺ Bmem cells were transcriptionally similar to effector-like memory cells, while T-bet^negFcRL5^neg Bmem cells exhibited stem-like central memory properties. FcRL5⁺ Bmem cells did not express plasma-cell-commitment factors but did express transcriptional, epigenetic, metabolic, and functional programs that poised these cells for antibody production. Accordingly, HA⁺ T-bet⁺ Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5⁺ Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet⁺ Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet⁺ Bmem cells were represented in the secondary ASC response to repeat vaccination, suggesting that this effector-like population predicts influenza vaccine durability and recall potential.

This guidance was developed to summarize current approaches to the potential transmission of swine-derived organisms to xenograft recipients, health care providers, or the public in clinical xenotransplantation. Limited specific data are available on the zoonotic potential of pig pathogens. It is anticipated that the risk of zoonotic infection in xenograft recipients will be determined by organisms present in source animals and relate to the nature and intensity of the immunosuppression used to maintain xenograft function. Based on experience in allotransplantation and with preclinical models, viral infections are of greatest concern, including porcine cytomegalovirus, porcine lymphotropic herpesvirus, and porcine endogenous retroviruses. Sensitive and specific microbiological assays are required for routine microbiological surveillance of source animals and xenograft recipients. Archiving of blood samples from recipients, contacts, and hospital staff may provide a basis for microbiological investigations if infectious syndromes develop. Carefully implemented infection control practices are required to prevent zoonotic pathogen exposures by clinical care providers. Informed consent practices for recipients and their close contacts must convey the lack of specific data for infectious risk assessment. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with carefully developed protocols for pretransplant assessment, syndrome evaluation, and microbiological monitoring.

Xenotransplantation of organs from swine in immunosuppressed human recipients poses many of the same challenges of allotransplantation relative to the risk for infection, malignancy, or graft rejection in proportion to the degree of immunosuppression and epidemiologic exposures. The unique features of xenotransplantation from pigs relative to infectious risk center on the potential for unusual organisms derived from swine causing productive infection, "xenosis" or "xenozoonosis," in the host. Based on experience in allotransplantation, the greatest hazard is due to viruses, due to the relative lack of information regarding the behavior of these potential pathogens in humans, the absence of validated serologic and molecular assays for swine-derived pathogens, and uncertainty regarding the efficacy of therapeutic agents for these organisms. Other known, potential pathogens (i.e., bacteria, fungi, parasites) tend to be comparable to those of humans. Concerns remain for unknown organisms in swine that may replicate in immunosuppressed humans. Clinical trials of genetically modified organs sourced from swine in immunosuppressed humans with organ failure are under development. Such trials require informed consent regarding potential infectious risks to the recipient, determination of breeding characteristics of swine, assessments of potential risks to the public and healthcare providers, consideration of ethical issues posed by this novel therapy, and defined strategies to monitor and address infectious episodes that may be encountered by healthcare teams. Clinical trials in xenotransplantation will allow improved definition of potential infectious risks.

Pharmacologic immunosuppression is required for the success of uterus transplantation but can provoke several complications for the transplant recipient. In this review, we discuss the immunologic complications that can occur in the uterus transplant recipient. First, we provide the latest update on immunosuppression regimens used by programs throughout the world. Next, we discuss the prevalence, mechanisms, treatment, and outcome of rejection in uterus transplant recipients. Finally, we discuss infectious complications of varying severity alongside their treatment and impact.

BACKGROUND:(DRE) in this patient population. METHODS:We conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within 1 year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest. RESULTS: < .001). CONCLUSIONS:bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared with VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.